610 Medizin und Gesundheit
Refine
Year of publication
- 2020 (867) (remove)
Document Type
- Article (678)
- Doctoral Thesis (103)
- Preprint (66)
- Contribution to a Periodical (10)
- Part of Periodical (6)
- Book (3)
- Master's Thesis (1)
Has Fulltext
- yes (867)
Keywords
- COVID-19 (20)
- inflammation (17)
- SARS-CoV-2 (11)
- quality of life (8)
- Quality of life (7)
- biomarker (7)
- cancer (7)
- macrophage (7)
- obesity (7)
- ADHD (6)
- depression (6)
- MRI (5)
- Machine learning (5)
- immunotherapy (5)
- pain (5)
- polytrauma (5)
- stroke (5)
- ACLF (4)
- EEG (4)
- Epilepsy (4)
- HIV (4)
- Inflammation (4)
- Rare diseases (4)
- Stroke (4)
- TAVI (4)
- aortic stenosis (4)
- autophagy (4)
- bipolar disorder (4)
- bladder cancer (4)
- breast cancer (4)
- cognition (4)
- coronavirus (4)
- cytokines (4)
- drug resistance (4)
- exercise (4)
- portal hypertension (4)
- schizophrenia (4)
- tumor microenvironment (4)
- Abdominal aortic aneurysm (3)
- Aortic stenosis (3)
- Biomarkers (3)
- Cardiovascular magnetic resonance (3)
- Cirrhosis (3)
- DNA methylation (3)
- Diagnostics (3)
- Diagnostik (3)
- Endovascular repair (3)
- Gesundheitsökonomie (3)
- Health economics (3)
- Heart failure (3)
- Human behaviour (3)
- Hypoxia (3)
- Infections (3)
- Macrophages (3)
- Magnetic resonance imaging (3)
- Mortality (3)
- NASH (3)
- Offene Versorgung (3)
- Open repair (3)
- Peri-implantitis (3)
- Postural control (3)
- Register (3)
- Registries (3)
- Registry (3)
- Strength training (3)
- Treatment (3)
- acute-on-chronic liver failure (3)
- apoptosis (3)
- attention (3)
- child (3)
- chimeric antigen receptor (3)
- complications (3)
- cytotoxicity (3)
- epilepsy (3)
- glioblastoma (3)
- glioma (3)
- hippocampus (3)
- integrins (3)
- iron (3)
- machine learning (3)
- macrophages (3)
- mesenchymal stromal cells (3)
- miRNA (3)
- microRNA (3)
- microbiome (3)
- migration (3)
- neuroblastoma (3)
- neurodegeneration (3)
- outcome (3)
- ovarian cancer (3)
- physical activity (3)
- precision medicine (3)
- prevalence (3)
- prevention (3)
- proliferation (3)
- prostate cancer (3)
- proteostasis (3)
- psoriasis (3)
- reactive oxygen species (3)
- sulforaphane (3)
- toxicity (3)
- 3D printing (2)
- 3D rapid prototyping (2)
- AML (2)
- ATP (2)
- Abdominelles Aortenaneurysma (2)
- Alzheimer’s disease (2)
- Artificial intelligence (2)
- Ascites (2)
- Ataxia telangiectasia (2)
- Autism spectrum disorder (2)
- BMI (2)
- Bibliometrics (2)
- Bladder cancer (2)
- Borrelia (2)
- CD19 (2)
- CD44 (2)
- CNN (2)
- Cancer (2)
- Cardiology (2)
- Cerebrospinal fluid (2)
- Children (2)
- Clinical decision support systems (2)
- Cohort studies (2)
- Computer-assisted diagnosis (2)
- Critical care (2)
- DTI (2)
- Database searching (2)
- Datenschutz (2)
- Dementia (2)
- Depression (2)
- Emergency room (2)
- Endoscopy (2)
- Endovaskuläre Behandlung (2)
- Epidemiology (2)
- Erweiterter Suizid (2)
- Europe (2)
- Extended suicide (2)
- Gemeinschaftliche Selbsttötung (2)
- Gene expression (2)
- Gene regulation (2)
- General practice (2)
- Genetics (2)
- Germany (2)
- Glioma (2)
- HIV-1 (2)
- Healthy adults (2)
- Hepatocellular carcinoma (2)
- IDH mutation (2)
- IL-10 (2)
- Immunohistochemistry (2)
- Immunological methods (2)
- Immunologische Methoden (2)
- Immunology (2)
- In vitro (2)
- Klebsiella pneumoniae (2)
- Klinische Ergebnisse (2)
- Knochenersatzmaterial (2)
- Krankheit (2)
- Language (2)
- Lebensqualität (2)
- Liver diseases (2)
- Liver transplantation (2)
- Long-term potentiation (2)
- MSD (2)
- Medical research (2)
- Metaanalysis (2)
- Morbidity (2)
- Morphology (2)
- Multiple sclerosis (2)
- Myocardial perfusion (2)
- NADPH oxidase (2)
- NAFLD (2)
- Neurology (2)
- Neurons (2)
- Notaufnahme (2)
- Object vision (2)
- Outcome (2)
- PCR (2)
- Patient blood management (2)
- Patients (2)
- Pneumonia (2)
- Preventive medicine (2)
- Public health (2)
- Radiomics (2)
- Remuneration (2)
- Seizure (2)
- Suicide pact (2)
- Survey (2)
- Transfusion (2)
- Treatment outcome (2)
- Validation (2)
- Vergütung (2)
- Wearable cardioverter-defibrillator (2)
- Women (2)
- acute lymphoblastic leukemia (2)
- adaptation (2)
- adolescents (2)
- adult (2)
- aging (2)
- alveolar ridge augmentation (2)
- animal experiment (2)
- antiepileptic drugs (2)
- augmentation (2)
- bibliometrics (2)
- biomarkers (2)
- body mass index (2)
- cardiac surgery (2)
- cerebral hemorrhage (2)
- cerebral venous thrombosis (2)
- chemoresistance (2)
- children (2)
- cirrhosis (2)
- cleaning (2)
- clinical studies (2)
- coagulopathy (2)
- combination therapy (2)
- complement (2)
- connective tissue (2)
- continuous performance test (2)
- curcumin (2)
- cystic fibrosis (2)
- cytomegalovirus (2)
- data science (2)
- decompensated liver cirrhosis (2)
- delirium (2)
- dental education (2)
- dental implants (2)
- dental profession (2)
- dentoalveolar surgery (2)
- diabetes mellitus (2)
- direct-acting antivirals (2)
- drug discovery (2)
- elderly (2)
- electroencephalography (2)
- environmental tobacco smoke (2)
- evolution (2)
- fascia (2)
- fibroblasts (2)
- fibrosis (2)
- flow cytometry (2)
- gait analysis (2)
- growth (2)
- hepatic encephalopathy (2)
- hepatocellular carcinoma (2)
- histology (2)
- hyperactivity (2)
- hypoxia (2)
- immunity (2)
- immunosuppression (2)
- impulsivity (2)
- infection (2)
- innate immunity (2)
- integrin (2)
- joint contact forces (2)
- kidney (2)
- liver (2)
- liver cirrhosis (2)
- lung cancer (2)
- lung function (2)
- lymphocytes (2)
- mTOR (2)
- mass spectrometry (2)
- metformin (2)
- mitochondria (2)
- multiple sclerosis (2)
- musculoskeletal disorders (2)
- musculoskeletal modeling (2)
- natural killer cells (2)
- neural oscillations (2)
- neurocognition (2)
- oncology (2)
- oral and maxillofacial surgery (2)
- pancreatic cancer (2)
- patient blood management (2)
- periodontitis (2)
- polygenic risk score (2)
- post-translational modifications (2)
- prognosis (2)
- protein degradation (2)
- protein synthesis (2)
- proteome (2)
- proteomics (2)
- public health (2)
- renal cell carcinoma (2)
- resistance training (2)
- risk factors (2)
- risk prediction (2)
- screening (2)
- sepsis (2)
- severe acute respiratory syndrome coronavirus 2 (2)
- simulation training (2)
- sphingosine 1-phosphate (2)
- sphingosine 1-phosphate receptor (2)
- spinal dural leaks (2)
- stress (2)
- superficial siderosis (2)
- surgery (2)
- survival (2)
- survivin (2)
- thrombosis (2)
- thymus (2)
- transcriptome (2)
- transplantation (2)
- tumor growth (2)
- tumor progression (2)
- von Willebrand factor (2)
- (cardiac) surgery (1)
- 14-3-3 gene family (1)
- 16 segment AHA model (1)
- 16S rRNA sequencing (1)
- 19F MR spectroscopy (1)
- 1H MR spectroscopy (1)
- 2'-deoxyguanosine riboswitch (1)
- 2-hydroxyglutarate (1)
- 2019-nCoV (1)
- 3,4-DCA; biotransformation (1)
- 3-hydroxyanthranilic acid (1)
- 3D printed cell-free scaffold (1)
- 3D-Druck (1)
- 4-fluoroamphetamine (1)
- 9-HODE (1)
- A-FFIP (1)
- A2BP1 (1)
- AAA+ disaggregase (1)
- ABC transporters (1)
- ABCB1 (1)
- ABCC1 (1)
- ACE-Bestimmung (1)
- ADAMTS-13 (1)
- ADAMTS13 (1)
- ADGRE1 (1)
- ADHD differential diagnosis (1)
- ADHS (1)
- AKI (1)
- ALL (1)
- AMH (1)
- AML – acute myeloid leukemia (1)
- ARDS (1)
- ASD-specific (1)
- ASPECTS (1)
- ATP binding (1)
- Abductor pollicis longus (1)
- Ablation (1)
- Abrasion (1)
- Absenteeism (1)
- Absorption modeling (1)
- Abusive head trauma (AHT) (1)
- Access (1)
- Accumulated degree days (1)
- Acellular dermis (1)
- Acoustics (1)
- Action potentials (1)
- Acute HIV infection (1)
- Acute appendicitis (1)
- Acute elbow dislocation (1)
- Acute hospital (1)
- Acute lymphoblastic leukemia (1)
- Acute lymphocytic leukaemia (1)
- Acute-on-chronic subdural hematoma (1)
- Addison’s disease (1)
- Adenosine (1)
- Adherence (1)
- Adipose tissue (1)
- Administrative claims data (1)
- Advanced breast cancer (1)
- Adverse drug reaction (1)
- Afrikanische Schlafkrankheit (1)
- Age determination (1)
- Age determination by skeleton (1)
- Age groups (1)
- Aging (1)
- Albumin ratio (1)
- Algorithms (1)
- Alkaloid (1)
- Allergic rhinitis (1)
- Allgemeinmedizin (1)
- Allogeneic (1)
- Alpha oscillations (1)
- Alzheimer's disease (1)
- Amino acid analysis (1)
- Amisulpride (1)
- Amitriptyline (1)
- Anal cancer (1)
- Anandamide (1)
- Anatomy (1)
- Anderson–Fabry (1)
- Andropogon virginicus (1)
- Angiogenesis (1)
- Angiotensin Converting Enzyme (1)
- Angiotensin-converting enzyme (1)
- Animal model (1)
- Anterior cruciate ligament reconstruction (1)
- Anti-CMV IgG (1)
- Anti-inflammatory (1)
- Anti-rheumatic agents (1)
- Anticholinergic (1)
- Anticoagulant (1)
- Anticoagulant therapy (1)
- Anticoagulants (1)
- Anticoagulation (1)
- Antidepressiva (1)
- Antigens/Peptides/Epitopes (1)
- Antihormone therapy (1)
- Antiviral immune response (1)
- Aortic input function (1)
- Apoptosis (1)
- Appendectomy (1)
- Aquilegia (1)
- Arbeitsgedächtnis (1)
- Arrhythmia syndromes (1)
- Arthroplasty (1)
- Ataxia score (1)
- Athletes (1)
- Atm (1)
- Atrial fibrillation (1)
- Attention deficit (1)
- Auditory cortex (1)
- Auditory midbrain (1)
- Auditory system (1)
- Aufmerksamkeit (1)
- Aufmerksamkeitsleistung (1)
- Autoimmune vasculopathy (1)
- Autologous biomaterial (1)
- Autopsy (1)
- Awareness campaign (1)
- Axiography (1)
- B cells (1)
- B-cell lymphoma (1)
- B-cell receptor (1)
- BAG3 (1)
- BCL6 (1)
- BCX7353 (1)
- BDNF (1)
- BET inhibitor (1)
- BEZ235 (1)
- BFIS (1)
- BG-index (1)
- BIRC5 (1)
- BK channel (1)
- BMC (1)
- BRD4 (1)
- Bacterial abundance (1)
- Bagatelltrauma (1)
- Bakterien (1)
- Bakterientest (1)
- Balloon-expandable TAVI (1)
- Bauchaortenaneurysma (1)
- Bee venom allergy (1)
- Begriffsbestimmung (1)
- Belastung (1)
- Benign enlargement of the subarachnoid spaces (BESS) (1)
- Benign pulmonary diseases (1)
- Benigne Lungenerkrankungen (1)
- Bestimmungsmethoden (1)
- Bestrahlung (1)
- Betriebliche Gesundheitsförderung (1)
- Bewegungsanalyse mit Inertialsensoren (1)
- Bewegungsstörung (1)
- Bildgebung (1)
- BioID (1)
- Bioavailability prediction (1)
- Biomarker (1)
- Biopsy (1)
- Bleeding (1)
- Blocked occlusion (1)
- Blood flow (1)
- Body limbs (1)
- Body measurements (1)
- Body modification (1)
- Body temperature (1)
- Bone defect (1)
- Bone regeneration (1)
- Bone remodelling (1)
- Bone substitute (1)
- Bone tissue engineering (1)
- Brain asymmetry (1)
- Brain injuries (1)
- Brain size I (1)
- Brain structure (1)
- Brain tumor surgery (1)
- Brain tumors (1)
- Brain-stimulus synchrony (1)
- Breast cancer survivers (1)
- Breathing (1)
- Brustkrebs (1)
- Burden (1)
- Burden of illness (1)
- Büroangestellte (1)
- C1 inhibitor (1)
- C2 domain (1)
- CAD/CAM (1)
- CAKUT (1)
- CAR (1)
- CCL2 (1)
- CD107-Assay (1)
- CD3 (1)
- CD34 + cells (1)
- CD4 binding site (1)
- CD41 (1)
- CD49d (1)
- CD62P (1)
- CD8+ T cell (1)
- CDI (1)
- CDK9 (1)
- CEBPD (1)
- CIRS (1)
- CLP (1)
- CMVepidemiology (1)
- COINS (1)
- COMP (1)
- COVID 19 pandemic (1)
- CPT1A (1)
- CRE-dependent transcription (1)
- CRISPR/Cas9 (1)
- CUELA system (1)
- CXCL10 (1)
- CXCR3 (1)
- Callous-unemotional traits (1)
- Calpain (1)
- Cancer check up (1)
- Cancer treatment (1)
- Candida spp (1)
- Cannabidiol (1)
- Capnography (1)
- Cardiac acoustic biomarkers (1)
- Cardiac arrest (1)
- Cardiac masses (1)
- CardioMEMS™ HF system (1)
- Careers (1)
- Caspase-8 (1)
- Cell death and immune response (1)
- Cell staining (1)
- Cell-based therapies (1)
- Cellular neuroscience (1)
- Central nervous system (1)
- Cerebellum (1)
- Cerebral hypoperfusion (1)
- Cerebrovascular disorders (1)
- Checkpoint inhibitor (1)
- Chemoradiation (1)
- Chemoradiotherapy (1)
- Chemotherapie (1)
- Chemotherapy (1)
- Child (1)
- Child abuse (1)
- Child health (1)
- Children and adolescents (1)
- Chimiothérapie (1)
- Chirurgie (1)
- Chromatin accessibility (1)
- Chromatin conformation (1)
- Chronic conditions (1)
- Chronic depression (1)
- Chronic inflammation (1)
- Chronology of disease (1)
- Classification (1)
- Clavien–Dindo classification (1)
- Climate inequity (1)
- Clinical genetics (1)
- Clinical trial (1)
- Clinical trials (1)
- Clostridium (1)
- Clustering coefficients (1)
- Coagulation (1)
- Coagulopathy management (1)
- Cognition (1)
- Cognitive behavioral therapy (1)
- Cognitive impairment (1)
- Cognitive neurology (1)
- Cold hardiness (1)
- Cold tolerance (1)
- Collagen-based biomaterial (1)
- Colonic neoplasms (1)
- Combo® DTS (1)
- Comparators (1)
- Complications (1)
- Compression stocking (1)
- Computed axial tomography (1)
- Computer hardware (1)
- Computer science (1)
- Computer software (1)
- Computer-aided drug design (1)
- Computers (1)
- Concept paper (1)
- Conduct disorder (1)
- Conduct problems (1)
- Confinement (1)
- Congenital CMVinfection (1)
- Congenital anomalies (1)
- Congenital diaphragmatic hernia (1)
- Connectivity (1)
- Conservative treatment (1)
- Constitution (1)
- Continuous Process Verification (1)
- Control (1)
- Cooperation (1)
- Copy number (1)
- Coronary artery disease (1)
- Coronavirus (1)
- Cortical degeneration (1)
- Cortical thickness (1)
- Cp (1)
- Cpk (1)
- Craniomaxillofacial injuries (1)
- Critical Online Reasoning Assessment (1)
- Critical size (1)
- Croatia (1)
- Crohn's disease (1)
- Crohn’s disease (1)
- CspA (1)
- CspZ (1)
- Curriculum (1)
- Cyp46a1 (1)
- CysLTR1 (1)
- Cysteine‐Rich Domain (CRD) (1)
- Cystic fibrosis (1)
- Cytokines (1)
- Cytomegalovirus (CMV) (1)
- DAMPs (1)
- DBS (1)
- DFNB9 (1)
- DILI (1)
- DNA damage (1)
- DNA damage response (1)
- DNA sequence analysis (1)
- DNase1-seq (1)
- DRG (1)
- DST (1)
- DYRK1A (1)
- Darunavir (1)
- Data processing (1)
- Data protection (1)
- Data science (1)
- Datenverarbeitung (1)
- Decision making (1)
- Decontamination (1)
- Deep vein thrombosis (1)
- Defibrillation (1)
- Dehnen (1)
- Delegation (1)
- Demenz (1)
- Density equalizing mapping (1)
- Density-equalizing mapping (1)
- Dental air (1)
- Dental casts (1)
- Dental implant (1)
- Dental implants (1)
- Dental practice (1)
- Dental students (1)
- Determination method (1)
- Developmental disorders (1)
- Diabetes mellitus (1)
- Diagnosis (1)
- Diagnosis related groups (1)
- Diagnostic algorithm (1)
- Diagnostic error (1)
- Diagnostic markers (1)
- Differential diagnosis (1)
- Diffuse large B-cell lymphoma (1)
- Disabilities (1)
- Disaster victim identification (1)
- Disc herniation (1)
- Diseases (1)
- Disintegration (1)
- Distress screening (1)
- Distribution limits (1)
- Dopamine (1)
- Double suicide (1)
- Double-blind placebo-controlled trial (1)
- Douleur (1)
- Downy mildew (1)
- Dravet syndrome (1)
- Drug permeability (1)
- Drug susceptibility testing (1)
- Dural onlays (1)
- Dysphagia (1)
- Désir d’enfant (1)
- E-NTPDase (1)
- E3 ligase (1)
- EBM (1)
- EEG reference choices (1)
- EGFR (1)
- EGFR pathway (1)
- EGFRvIII mutation (1)
- EGR1-dependent transcription (1)
- ELISA (1)
- EMR1 (1)
- EMT (1)
- EQIP (1)
- ERBB2 (HER2/neu) (1)
- ERK3 (1)
- ES (1)
- ESMO-MCBS (1)
- Early intervention (1)
- Ebola virus (1)
- Echovirus-30 (1)
- Ecto-5'-nucleotidase (1)
- Edoxaban (1)
- Education (1)
- Einstellungen (1)
- Einwilligungsfähigkeit (1)
- Eisenmangel (1)
- Ejection fraction (1)
- Elderly (1)
- Electrical stimulation (1)
- Embryos (1)
- Emergency treatment (1)
- Emotions (1)
- End-of-life decisions (1)
- Endocrinology (1)
- Endometrial carcinoma (1)
- Endometriome (1)
- Endométriomes (1)
- Endothelial cells (1)
- Endothelial protein C receptor (1)
- Endovaskuläre Versorgung (1)
- Endpoints (1)
- Enterobacteriaceae (1)
- Entscheidungsassistenz (1)
- Epidemiological data (1)
- Epidural abscess (1)
- Epigenetics (1)
- Epilepsie (1)
- Episodic memory (1)
- Epstein-Barr virus (1)
- Erdnussallergie (1)
- Ergonomic analysis (1)
- Ergonomie am Arbeitsplatz (1)
- Ergonomische Analyse (1)
- Erregerspektrum der Tonsillitis (1)
- Erwachsene (1)
- Evaluation (1)
- Evidence based medicine (1)
- Evidence-based dentistry (1)
- Evidence-based medicine (1)
- Evidenzbasierte Medizin (1)
- Ewing sarcoma (1)
- Exercise challenge (1)
- Exercise therapy (1)
- Exercise-induced asthma (1)
- Exhaled nitric oxide (1)
- External-/self-assessment (1)
- Eye movements (1)
- Eye tracking (1)
- F4/80 (1)
- F508del homozygous (1)
- FBK-R23 (1)
- FDM (1)
- FET (1)
- FEV1 (1)
- FFF (1)
- FHIR (1)
- FLT3-ITD (1)
- FTMT (1)
- Factor H (1)
- Fasting (1)
- Feedback (1)
- Female subjects (1)
- Ferritinophagy (1)
- Ferroptose (1)
- Ferroptosis (1)
- Fertilität (1)
- Fertilité (1)
- Fibromyalgia (1)
- Finevo (1)
- Fingolimod (1)
- First-line regimen (1)
- Five-Konzept (1)
- Fluid therapy (1)
- Forced expiratory volume in 1 s (1)
- Forensic entomology (1)
- Forensic examination (1)
- Fourier analysis (1)
- Fracture (1)
- Fracture type (1)
- Fragebogenentwicklung (1)
- Fresh frozen plasma (1)
- Functional characterization (1)
- Functional clustering (1)
- Functional mitral regurgitation (1)
- G-CSF (1)
- G-protein-coupled receptors (1)
- G2A receptor (1)
- GABA (1)
- GCN (1)
- GFAP (1)
- GHQ-28 (1)
- GIRD (1)
- GLA deficiency (1)
- GPCR (1)
- GWAS (1)
- Gait analysis (1)
- Gas gangrene (1)
- Gastrocnemius muscles (1)
- Gastroschisis (1)
- Gene expression prediction (1)
- Genetic heart disease (1)
- Genetic syndromes (1)
- Geoffrey Burnstock (1)
- Geographical disparities (1)
- Gerontologie (1)
- Geschichte 1663-1748 (1)
- Geschlecht (1)
- Gesundheit (1)
- Gesundheitsamt (1)
- Gesundheitsberichterstattung (1)
- Gesundheitsbildung (1)
- Gesundheitserziehung (1)
- Gesundheitsförderung (1)
- Gesundheitswissenschaften (1)
- Glioblastom (1)
- Global warming (1)
- Graph theory (1)
- Gray matter volume (1)
- Green Tobacco Sickness (GTS) (1)
- Greenhouse effect (1)
- Guided bone regeneration (GBR) (1)
- Guided tissue regeneration (GTR) (1)
- HADS (1)
- HAE (1)
- HBV filaments (1)
- HBV genotypes (1)
- HBV surface protein (1)
- HCC (1)
- HCC recurrence (1)
- HCV (1)
- HDAC (1)
- HDAC and BET inhibitor (1)
- HDAC inhibitor (1)
- HDAC4 (1)
- HEUS (1)
- HEV (1)
- HFrEF (1)
- HHUSD (1)
- HIBCPP cells (1)
- HIFT (1)
- HILI (1)
- HIV-1 escape restriction (1)
- HLA DQ haplotypes (1)
- HLA class I (1)
- HNSCC (1)
- HOSO (1)
- HRM (1)
- Haematocrit (1)
- Haemodynamic monitoring (1)
- Hausarztmangel (1)
- HbA1c (1)
- HeLa cells (1)
- Health care (1)
- Health care sector (1)
- Health education and awareness (1)
- Health literacy (1)
- Health policy (1)
- Health services (1)
- Healthcare costs (1)
- Healthcare resource utilization (1)
- Health‐related quality of life (1)
- Heat shock protein 27 (1)
- Hematologic malignancies (1)
- Hematoxylin staining (1)
- Hemispheric specialization (1)
- Hemodynamics (1)
- Hepatic encephalopathy (1)
- Hepatitis C virus (1)
- Heregulin (1)
- Heterogeneity (1)
- HiC (1)
- HiChIP (1)
- High oblique sagittal osteotomy (1)
- Hippocampal excitability (1)
- Hippocampus (1)
- Histological analysis (1)
- Histology (1)
- Histoplasma qPCR (1)
- History (1)
- Hmox1 (1)
- HoLEP (1)
- Hodgkin lymphoma (1)
- Hodgkin’s lymphoma (1)
- Homicide-suicide (1)
- Homizid-Suizid (1)
- Hospital case volume (1)
- Hospitalization (1)
- House dust mite allergy (1)
- Human (1)
- Human immunodeficiency virus (HIV) (1)
- Hymenoptera venom immunotherapy (1)
- Hyperactivity (1)
- Hyperscanning (1)
- Hyponatremia (1)
- Hypoxia-inducible factor-1α (HIF-1α) (1)
- Höchstrichterliche Rechtsprechung (1)
- ICAM-1 (1)
- ICD (1)
- IDH1 inhibitor (1)
- IDO1 (1)
- IFA (1)
- IFN-γ expression (1)
- IKKε (1)
- IL-1β (1)
- IL-6 (1)
- ISR (1)
- IV iron (1)
- IVD degeneration (IVDD) (1)
- Iatrochemie (1)
- Iatrochemistry (1)
- Identification (1)
- Identifikation (1)
- Identifizierung von Katastrophenopfern (1)
- Idiopathische Dystonie (1)
- IgG (1)
- Image processing (1)
- Image processing (computer-assisted) (1)
- Immune suppression (1)
- Immune system (1)
- Immunomodulatory agents (1)
- Immunotherapy (1)
- Implant osseointegration (1)
- Implementación (1)
- Implementation (1)
- Imrt (1)
- In vivo (1)
- Induced membrane technique (1)
- Inducible nitric oxide synthase (iNOS) (1)
- Induction chemotherapy (1)
- Inertial motion capture (1)
- Infektionen (1)
- Inferior colliculus (1)
- Inflammatory bowel disease (1)
- Inflammatory pattern (1)
- Injury (1)
- Injury Severity Score (ISS) (1)
- Innate immunity (1)
- Integrated Pulmonary Index (1)
- Integration (1)
- IntelliCage (1)
- Intelligence (1)
- Intensive care (1)
- Interferons (1)
- Internet (1)
- Interoperability (1)
- Interposition (1)
- Interstitial pneumonia (1)
- Interview (1)
- Intoxication (1)
- Intoxikation (1)
- Intravenous antibiotic therapy (1)
- Intravenous injections (1)
- Invasive species (1)
- Ireb2 (1)
- Iron (1)
- Isocitrate dehydrogenase (1)
- JNK (1)
- Joint actions (1)
- Joint loading (1)
- Jumping (1)
- K-homology RNA-binding domain (1)
- KOOS IV (1)
- Ki-67/MIB1 (1)
- Ki67 transgenic c‐myc/TGFα mice (1)
- Kidney diseases (1)
- Kidney neoplasm (1)
- Kinder (1)
- Kinderwunsch (1)
- Kinds of diseases (1)
- Kinematic analysis (1)
- Knees (1)
- Kognitive Beeinträchtigungen (1)
- Konzeptpapier (1)
- Krankenhausfallaufkommen (1)
- Krankheitskosten (1)
- Körpermaße (1)
- Körpermodifizierung (1)
- L-DOPA (1)
- LBP (1)
- LIR interaction, (1)
- LPS (1)
- Lactobacillus (1)
- Landarztprogramm (1)
- Langstreckige Knochendefekte (1)
- Language delay (1)
- Late gadolinium enhancement (1)
- Left hemisphere (1)
- Legal considerations (1)
- Legs (1)
- Lennox-Gastaut syndrome (1)
- Leukemia (1)
- Leukämie (1)
- Lipodystrophy (1)
- Liver transplant (1)
- Local IgE (1)
- Local allergic rhinitis (1)
- Locally advanced (1)
- Lockdown (1)
- Loco-regional control (1)
- Long non-coding RNAs (1)
- Longchain polyunsaturated fatty acids (1)
- Loving kindness meditation (1)
- Low-dose ionizing radiation (1)
- Low-dose radiation therapy (1)
- Lower back pain (1)
- Lung cancer (1)
- Lung development (1)
- Lung function (1)
- Lung ultrasound (1)
- Lungenerkrankungen (1)
- Lymph nodes (1)
- Lymphocytes (1)
- Lymphoma (1)
- Lysophosphatidic acids (1)
- M. Intracellulare (1)
- M. avium (1)
- M. avium complex (1)
- M. chimaera (1)
- MAGGIC score (1)
- MAPK6 (1)
- MCAO (1)
- MHC (1)
- MICA (1)
- MM-121 (1)
- MMP14 (1)
- MODY (1)
- MR-spectroscopy (1)
- MS (1)
- MYC (1)
- Machine learning algorithms (1)
- Machine-learning (1)
- Macroautophagy (1)
- Macrophage polarization (1)
- Malaria (1)
- Mammakarzinom (1)
- Management (1)
- Marker genes (1)
- Market Access (1)
- Masquelet technique (1)
- Mass disaster (1)
- Massenkatastrophe (1)
- Massenspektrometrie (1)
- Master Plan 2020 (1)
- Masterplan 2020 (1)
- Maxillofacial surgery (1)
- Mean erythrocyte volume (1)
- Medical education (1)
- Medical implants (1)
- Medical law (1)
- Medical risk factors (1)
- Medical studies (1)
- Medicinal chemistry (1)
- Medizin (1)
- Medizinrecht (1)
- Medizinstudierende (1)
- Medizinstudium (1)
- Meldepflicht (1)
- Membrane potential (1)
- Memory consolidation (1)
- Memory quality (1)
- Mesenchymal stromal cells (MSC) (1)
- Mesh (1)
- Meta-analysis (1)
- Metabolic diseases (1)
- Metastatic (1)
- Metta (1)
- Michael acceptor (1)
- MicroRNA-181a (1)
- Microbiology (1)
- Microfluidics (1)
- Microglial cells (1)
- Microparticles (1)
- Microphysiological models (1)
- Microstates (1)
- Midwifery (1)
- Mindfulness (1)
- Minimally invasive surgical procedures (1)
- Minor injury (1)
- Mitochondrial dysfunction (1)
- MitraClip (1)
- Mobilization (1)
- Molecular autopsy (1)
- Molecular diagnostic testing (1)
- Molecular neuroscience (1)
- Monetary incentive delay (1)
- Mongolian spot (1)
- Monitoring (1)
- Monocytes (1)
- Morphologie (1)
- Motivational situation (1)
- Motivationslage (1)
- Motor control (1)
- Motor cortex (1)
- Mouse models (1)
- Mucomaix® matrix (1)
- Multidrug-resistance (1)
- Multimedication (1)
- Multimorbidity (1)
- Multiparametric MRI (1)
- Multiplate (1)
- Multiple Sklerose (1)
- Multiple-indication review (1)
- Mundhöhlenkarzinome (1)
- Muscle functions (1)
- Musculoskeletal diseases (1)
- Muskuloskelettale Erkrankungen (1)
- Mutation databases (1)
- Muttermilch (1)
- Mutual information (1)
- Myocardial infarction (MI) (1)
- Myocardial injury (1)
- Myocardial segmentation (1)
- Myonecrosis (1)
- Mφs (1)
- N-glycoproteome (1)
- N2 (1)
- NAFL (1)
- NCOA4 (1)
- NCoR1 (1)
- NDBI (1)
- NF-κB (1)
- NF-κB pathway (1)
- NF-кB (1)
- NIRS (1)
- NK-ZELL-BASIERTER IMMUNTHERAPIE (1)
- NK-ZELLEN (1)
- NKG2D (1)
- NLRP3 inflammasomes (1)
- NMES (1)
- NMR spectroscopy (1)
- NOTCH (1)
- NPH insulin (1)
- NREM sleep (1)
- NS1608 (1)
- NSE (1)
- NTM (1)
- Nachtschattengewächs (1)
- Natural sounds (1)
- Necrotizing fasciitis (1)
- Negative appendectomy rate (1)
- Nek1 (1)
- Neonatal brain damage (1)
- Neonatal surgery outcome (1)
- Nephrectomy (1)
- Nesplora Aquarium (1)
- Network models (1)
- Network motifs (1)
- Neural circuits (1)
- Neural networks (1)
- Neurocognition (1)
- Neurodegeneration (1)
- Neurodevelopmental disorders (1)
- Neuron (1)
- Neuronal plasticity (1)
- Neuropathic pain (1)
- Neurophysiology (1)
- Neuropsychological testing (1)
- Neuropsychology (1)
- Neuroscience (1)
- Neurosurgery (1)
- Neurotransmitter (1)
- Nevus of Ito (1)
- Nevus of Ota (1)
- Next-generation sequencing (1)
- Nicotine (Nicotiana tabacum/ Nicotiana rustica) (1)
- Nicotinic acetylcholine receptors (1)
- Nikotin (Nicotiana tabacum/ Nicotiana rustica) (1)
- Nikotinerge Acetylcholinrezeptoren (1)
- Nivolumab (1)
- Non-abusive head trauma (NAHT) (1)
- Non-allergic-rhinitis (1)
- Non-apoptotic functions (1)
- Non-clear cell renal cell cancer (1)
- Non-small cell lung cancer (1)
- Non-tuberculous mycobacteria (1)
- Non-vitamin K antagonist oral anticoagulants (1)
- Nordic questionnaire (1)
- Normal distribution (1)
- Normative modeling (1)
- NoxO1 (1)
- Number of platelets (1)
- OGTT (1)
- OR time (1)
- OSA (1)
- OTSC Proctology (1)
- Obduktion (1)
- Obstetrics (1)
- Omphalocele (1)
- Oncology (1)
- Open Access (1)
- Opioids (1)
- Oppositional defant disorder (1)
- Optogenetics (1)
- Oral anticoagulation (1)
- Oral cancer (1)
- Organoids (1)
- Orphan nuclear receptor (1)
- Orthognathic surgery (1)
- Oryctolagus cuniculus (1)
- OspE (1)
- Osteoarthritis (1)
- Osteonecrosis (1)
- Outcomes (1)
- Ovarian cancer treatment (1)
- Ovarielle Reserve (1)
- Ovartoxizität (1)
- Overwintering (1)
- Oxygen (1)
- PARK2 (1)
- PBMC (peripheral blood mononuclear cells) (1)
- PBPK (1)
- PD-1 inhibitor (1)
- PDE inhibition (1)
- PDE‐5‐inhibitor (1)
- PEA-15 (1)
- PHGDH (1)
- PI3K/mTor inhibition (1)
- PKD (1)
- PKD/IC (1)
- PLSC (1)
- PRNT (1)
- PROM (1)
- PRRT2 (1)
- PSA screening (1)
- PSA-Screening (1)
- PV loop (1)
- PWI (1)
- PYGL (1)
- Paediatric trauma patients (1)
- Pain (1)
- Pain sensation (1)
- Palliative care (1)
- Parasympathetic (1)
- Parkinson's disease (1)
- Pathogenesis (1)
- Pathologists (1)
- Patient information materials (1)
- Patient outcome assessment (1)
- Patient reported outcomes (1)
- Patient safety (1)
- Patterns of care (1)
- Peanut allergy (1)
- Pediatric patients (1)
- Peer review (1)
- Pelvic (1)
- Percutaneous endoscopic gastrostomy (1)
- Performance Metrics (1)
- Pericardial effusion (1)
- Pericarditis (1)
- Periodontitis grades B and C (1)
- Periprocedural anticoagulation (1)
- Perrault syndrome (1)
- Persistent depressive disorder (1)
- Pgrmc1 (1)
- Phalangeal fractures (1)
- Pharma Management (1)
- Pharmaceutical (1)
- Pharmacology (1)
- Phase I clinical trial (1)
- Phase II trial (1)
- Phase rotors (1)
- Phenotypic plasticity (1)
- Philemon and Baucis (1)
- Philemon und Baucis (1)
- Phosphoproteome (1)
- Phylogeny (1)
- Physical activity (1)
- Physician-assisted suicide (1)
- Physicians (1)
- Pim-1 (1)
- Plantagearbeiter (1)
- Plantation workers (1)
- Plasma transfusion (1)
- Plasma usage (1)
- Platelet-rich fibrin (1)
- Polygenic risk score (1)
- Polypharmacy (1)
- Polysomnography (1)
- Polytrauma (1)
- Portal hypertension (1)
- Portal veins (1)
- Post mortem interval (1)
- Posture (1)
- Pp (1)
- Ppk (1)
- Praktisches Jahr (1)
- PreS1 deletion (1)
- Preclinical drug development (1)
- Prediction (1)
- Premotor cortex (1)
- Pressure distribution (1)
- Pressure measuring plate (1)
- Prevalence (1)
- Prevention (1)
- Pre‐Ligand Assembly Domain (PLAD) (1)
- Primary breast lymphoma (1)
- Primary care (1)
- Primary health care (1)
- Probability density (1)
- Probability distribution (1)
- Procalcitonin (1)
- Procedural skills (1)
- Process Capability (1)
- Process Performance (1)
- Process Validation (1)
- Professions (1)
- Progestatifs synthétiques (1)
- Prostata-specific antigen (1)
- Prostataspezifisches Antigen (1)
- Prostate cancer (1)
- Protease inhibitor therapy (1)
- Proteasome inhibitor (1)
- Protestantism (1)
- Prototypes (1)
- Präanalytik (1)
- Prävention (1)
- Pseudoprogression (1)
- Psycho-oncology (1)
- Psychological stress (1)
- Psychologische Beeinträchtigung (1)
- Psychology (1)
- Psychopharmaka (1)
- Psychosocial impact (1)
- Pteridine (1)
- Pulmonary edema (1)
- Pulmonary embolism (1)
- Pulmonary hypertension (1)
- Pulmonary hypoplasia (1)
- QOL (1)
- Qb-Test (1)
- QbTest® (1)
- Qualitative research (1)
- Quality Control (1)
- Quality indicators (1)
- Qualitätsindikatoren (1)
- Quantitative (q)T2 mapping (1)
- Quantitative magnetic resonance imaging (1)
- Quantitative research (1)
- Quantra (1)
- Quarantine (1)
- Questionnaire (1)
- Questionnaires (1)
- Quinolones (1)
- R406 (1)
- RAS (1)
- RBC (1)
- RBFOX1 (1)
- RDoC (1)
- RIPK1 (1)
- RNA chaperone (1)
- RNA structures (1)
- RNA therapeutics (1)
- RNAseq analysis (1)
- RRMS (1)
- RUCAM (1)
- RULA (1)
- Radiation exposure (1)
- Radical cystectomy (1)
- Radiotherapy (1)
- Radiothérapie (1)
- Ramadan (1)
- Randomised trial (1)
- Randomized controlled trial (1)
- Randomized controlled trials (1)
- Randomized trial (1)
- Rapid diagnostic test (1)
- Ratgeber (1)
- Real-time phase contrast (1)
- Rechtliche Würdigung (1)
- Rectal cancer (1)
- Reference values (1)
- Referenzwerte (1)
- Refractory ALL (1)
- Refractory AML (1)
- RegJoint™ (1)
- Regeneration (1)
- Regret (1)
- Regulatory Affairs (1)
- Relaxometrie (1)
- Reliability (1)
- Renal replacement therapy (1)
- Rescue medication (1)
- Research & Development (1)
- Research investment (1)
- Respiration (1)
- Respiratory distress syndrome (1)
- Resting-state (1)
- Retinal diseases (1)
- Retinoic acid (1)
- Retrospective studies (1)
- Return to work (1)
- Review (1)
- Reward (1)
- Rezidiv (1)
- Rhabdomyosarkom (1)
- Rheumatoid arthritis (1)
- Right hemisphere (1)
- Risk factors (1)
- Risk-stratification (1)
- Robotik (1)
- Roussel Uclaf Causality Assessment Method (1)
- Roux-en-Y gastric bypass (1)
- Running (1)
- Rush protocol (1)
- Récidive (1)
- Réserve ovarienne (1)
- S100b (1)
- S1P lyase (1)
- S1P receptors (1)
- S1P1–5 (1)
- S1PR4 (1)
- SARS‐CoV‐2 (1)
- SCA2 (1)
- SCN5A (1)
- SEAP (1)
- SENP (1)
- SF-36 (1)
- SIDS (1)
- SIRS (1)
- SKI II (1)
- SLC20A1 (1)
- SLUG (1)
- SMAD (1)
- SNORD95 (1)
- SPC (1)
- SPSS (1)
- STAT3 (1)
- SUMO (1)
- Safety (1)
- Sarcoidosis (1)
- Sarcomas (1)
- Sarkoidose (1)
- Saudi Arabia (1)
- Scaffold (1)
- Schlaganfall (1)
- Schmerz (1)
- Schädel-MRT (1)
- Seattle heart failure model (1)
- Second donation (1)
- Secular trend (1)
- Selbstmordpakt (1)
- Self-expandable TAVI (1)
- Seltene Erkrankungen (1)
- Semitendinosus tendon autograft (1)
- Senescence (1)
- Sensorimotor processing (1)
- Sepsis (1)
- Seribantumab (1)
- Serin (1)
- Serious injured children (1)
- Seroconverter (1)
- Seroprevalence (1)
- Serum biomarker (1)
- Sex (1)
- Sharp injuries (1)
- Shoulder injury (1)
- Shoulder luxation (1)
- Sialic acid (1)
- Sialinsäure (1)
- Side effects (1)
- Signal intensity (1)
- Signs and symptoms (1)
- Single-Molecule Localization Microscopy (SMLM) (1)
- Slc11a2 (1)
- Slc25a37 (1)
- Sleep (1)
- Sleep deprivation (1)
- Smac mimetic (1)
- Small molecules (1)
- Social brain (1)
- Social differences (1)
- Social information processing (1)
- Social participation (1)
- Socio-economic analysis (1)
- Socioeconomic analysis (1)
- Socioeconomic indices (1)
- Soft tissue infection (1)
- Software tools (1)
- Solanaceae (1)
- Sozialwissenschaften (1)
- Speech (1)
- Spine fractures (1)
- Spinocerebellar ataxia type 2 (1)
- Sports and exercise medicine (1)
- Stage at presentation (1)
- Standard dataset (1)
- Standard reference values (1)
- Standard value (1)
- State of Control (1)
- Statisitcal Control (1)
- Statisitcal Process Control Chart (1)
- Statistical data (1)
- Status epilepticus (1)
- Stem cell (1)
- Stereoelektroenzephalographie (1)
- Stereotaxie (1)
- Sterols (1)
- Stiffness (1)
- Streptokokken (1)
- Striatum (1)
- Stroke genetics (1)
- Störfaktoren (1)
- Sub-segmentation (1)
- Sub-zero exposure (1)
- Sudden death (1)
- Sudden infant death syndrome (1)
- Sunitinib (1)
- Supported Decision-making (1)
- Supreme court ruling (1)
- Surgeons (1)
- Surgery (1)
- Surgical and invasive medical procedures (1)
- Surgical therapy (1)
- Surveys (1)
- Suspension (1)
- Swallowing (1)
- Syllables (1)
- Sympathetic (1)
- Symptome (1)
- Synaptic plasticity (1)
- Synaptic transmission (1)
- Synthetische Gestagene (1)
- Systematic reviews (1)
- Szientometrie (1)
- Säkularer Trend (1)
- T cell receptor (1)
- T cells (1)
- T-Zellen (1)
- T-cell receptor (1)
- T-tubule system (1)
- T1 and T2 mapping (1)
- T2 (1)
- TAMs (1)
- TAPSE (1)
- TBK1 (1)
- TBSS (1)
- TDM (1)
- TGF-beta (1)
- TGF-β (1)
- TGFβ (1)
- TGR(mREN2)27 (1)
- THV (1)
- TLR2/6 (1)
- TRIMs (1)
- TRPA1 (1)
- TSC22D3 (1)
- TVT (1)
- Tabakkonsum (1)
- Tagging (1)
- Tamponade (1)
- Target validation (1)
- Targeted sequencing (1)
- Temsirolimus (1)
- Tendon incontinence repair (1)
- Tendon transplantation (1)
- Tendons (1)
- Tennis player (1)
- Terminology (1)
- Test assay (1)
- Tfrc (1)
- Therapie (1)
- Therapies (1)
- Therapy (1)
- Thrombotic thrombocytopenic purpura (1)
- Thrombozytenkonzentrat (1)
- Thrombozytentransfusion (1)
- Thumb carpometacarpal joint osteoarthritis (1)
- Tissue engineering (1)
- Tocilizumab (1)
- Todesart (1)
- Toll-like receptor (1)
- Tonsillitis (1)
- Torque (1)
- Total hip arthroplasty (1)
- Touchscreen (1)
- Toxicité ovarienne (1)
- Training history (1)
- Transcatheter Aortic Valve Implantation (1)
- Transcription regulation (1)
- Transcriptional regulatory elements (1)
- Transcriptome analysis (1)
- Transfusion practice (1)
- Transfusionszwischenfall (1)
- Transgenic mice (1)
- Transitional cell carcinoma (1)
- Translation proteomics (1)
- Transportation (1)
- TraumaRegister DGU® (TR-DGU) (1)
- Treatment costs (1)
- Treatment effectiveness (1)
- Treatment modification (1)
- Treatment rates (1)
- Treg (1)
- Treg cell (1)
- Trend Analysis (1)
- Trypanosoma brucei (1)
- Tumor marker (1)
- Tumor microenvironment (1)
- Tumormarker (1)
- Tumormikromilieu (1)
- Type 2 diabetes (1)
- Type of death (1)
- ULK4 (1)
- UPPS (1)
- USP28 (1)
- UV/Vis spectroscopy (1)
- Ubiquitin (1)
- Ubiquitin ligase (1)
- Ubiquitinome (1)
- Ulcerative colitis (1)
- Ultra-rush protocol (1)
- Umfrage (1)
- Unc-51-like kinase (1)
- Uncertainty (1)
- Undergraduate education (1)
- Undergraduates (1)
- Unfälle (1)
- Upper body posture (1)
- Urothelial cancer (1)
- VHH (1)
- VIGALL (1)
- VIM (1)
- VLA4 (1)
- Vascular endothelial growth factor (VEGF) (1)
- Veins (1)
- Venous thromboembolism (1)
- Ventricular arrhythmia (1)
- Ventricular arrhythmias (1)
- Vespid venom allergy (1)
- Videorasterstereography (1)
- Viral infection (1)
- Vmem (1)
- Volume therapy (1)
- Volumetrie (1)
- Volunteer donor (1)
- Vorsorgeuntersuchung (1)
- Voxel-based morphometry (VBM) (1)
- Watertight Dural closure (1)
- Wearable cardioverter‐defibrillator (1)
- Western diet (1)
- Winter survival (1)
- Wissenschaftstheorie (1)
- Workplace ergonomics (1)
- Wound care (1)
- Wound healing (1)
- Wounds (1)
- Wundversorgung (1)
- YM155 (1)
- YWHAE (1)
- YWHAZ (1)
- Year of practical training (1)
- Yellow fluorescent protein (1)
- Zink (1)
- [18F]FET PET (1)
- abnormality detection (1)
- abuse (1)
- abuso (1)
- academic medicine (1)
- acetylation (1)
- acetylcholine (1)
- acetylcholinesterase (1)
- acid dentine lysate (1)
- acidosis (1)
- acoustic emission (1)
- acquired drug resistance (1)
- actin dynamics (1)
- action sounds (1)
- action-effect association (1)
- activated clotting time measurement (1)
- activities of daily life (1)
- activity-based benefits (1)
- acupuncture (1)
- acute coronary syndromes (1)
- acute decompensation (1)
- acute decompensation of cirrhosis (1)
- acute kidney injury (1)
- acute myeloid leukaemia (1)
- acute respiratory distress syndrome (1)
- acute-on-chronic liver failure (ACLF) (1)
- acute‐on‐chronic liver failure (1)
- adaptive cardiac remodelling (1)
- adaptive immunity (1)
- adenovirus (1)
- adhesion (1)
- adiabatic saturation (1)
- adipose-derived mesenchymal stem/stromal cells (1)
- adjuvante Krebstherapie (1)
- adolescentes (1)
- adoptive cancer immunotherapy (1)
- adrenoceptors (1)
- adult and elderly patients (1)
- advanced care planning (1)
- adverse events (1)
- aerobic exercise (1)
- affective disorder (1)
- affective disorders (1)
- affinity purification (1)
- aftercare structures (1)
- age (1)
- aggressiveness (1)
- air flow (1)
- alcohol use disorder (1)
- alcoholic hepatitis (1)
- algorithm (1)
- alirocumab (1)
- alkaloid (1)
- allergy (1)
- allocation (1)
- allogeneic donor (1)
- allogeneic hematopoietic stem cell transplantation (1)
- alpha power (1)
- alpha-galactosidase A deficiency (1)
- alpharetroviral vector (1)
- alternative matrices (1)
- alternative oxidase (1)
- amblyopia (1)
- amino acid PET (1)
- amlexanox (1)
- amyloid beta-peptides (1)
- amyotrophic lateral sclerosis (ALS) (1)
- anaemia walk-in clinic (1)
- anal cancer (1)
- anemia (1)
- angiography (1)
- angiokeratoma diffuse (1)
- animal (1)
- animal model (1)
- annual bleeding rate (1)
- anti-chronic myeloid leukemia (1)
- anti-diabetes (1)
- anti-inflammatory agents (1)
- anti-inflammatory drug (1)
- anti-inflammatory effects (1)
- anti-skin aging (1)
- anti-tumor activity (1)
- antibiotic treatment (1)
- antibody tests (1)
- anticoagulation (1)
- antigen (1)
- antigen processing and presentation (1)
- antigenic variation (1)
- antigens of infectious origin (1)
- antioxidant defense (1)
- antioxidants (1)
- antireflux surgery (1)
- antiresorptive agents (1)
- antiseizure (1)
- antiviral (1)
- antiviral peptide (1)
- anxiety disorder (1)
- aprotinin (1)
- aptamers (1)
- arachidonate 12/15-lipoxygenase (Alox12/15) (1)
- arousal (1)
- artesunate (ART) (1)
- artificial intelligence (1)
- ascites (1)
- aspiration (1)
- aspirin (1)
- asthma (1)
- asthma phenotypes (1)
- astrogliosis (1)
- asymptomatic (1)
- ataxia telangiectasia (1)
- athletes (1)
- atopy (1)
- attention module (1)
- attention-deficit/hyperactivity disorder (1)
- atypical MAPK kinase (1)
- auditory cortex (1)
- auditory fMRI (1)
- auditory prediction (1)
- auditory processing (1)
- autism (1)
- autism spectrum disorder (1)
- autograft (1)
- autoimmune diabetes (1)
- autoimmune polyglandular syndrome type 2 (1)
- autoimmune thyroiditis (1)
- autoreactivity (1)
- back pain diagnosis (1)
- bacteria (1)
- bacterial translocation (1)
- balloon pulmonary angioplasty (1)
- barbell training (1)
- basal insulin (1)
- behavioral adverse events (1)
- benchmark standards (1)
- berotralstat (1)
- biglycan (1)
- bio imaging (1)
- bio-enabling formulations (1)
- bioactive lipids (1)
- bioavailability (1)
- biobank (1)
- biological maturation (1)
- bioluminescence (1)
- biomarker study (1)
- biopsy naïve (1)
- bipolare Störung (1)
- bladder cancer (BCa) (1)
- bladder exstrophy-epispadias complex (1)
- blinatumomab (1)
- blood (1)
- blood flow recovery (1)
- blood flow restriction (1)
- blood loss (1)
- blood pressure (1)
- blood transfusion (1)
- blood-brain barrier (1)
- blood-cerebrospinal fluid barrier (1)
- body dysmorphic disorder (1)
- body plethysmography (1)
- bone healing (1)
- bone marrow (1)
- bone marrow mononuclear cells (1)
- bone tissue regeneration (1)
- brain (1)
- brain anatomy (1)
- brain function (1)
- brain metastases (1)
- brain shift (1)
- brain tumor (1)
- brain-derived neurotrophic factor (1)
- brainstem (1)
- broad-range qPCR (1)
- broadly neutralizing antibodies (1)
- bronchiolitis obliterans syndrome (1)
- buccal mucosal graft urethroplasty (1)
- bundle (1)
- butyrylcholinesterase (1)
- bypass (1)
- cART (1)
- cBioPortal (1)
- cHL (1)
- caesarean scar (1)
- caesarean section (1)
- calcium handling (1)
- calcium-sensor (1)
- cancer associated fibroblasts (1)
- cancer immunobiology (1)
- cancer information (1)
- cancer specific survival (1)
- candidemia (1)
- canine cancer (1)
- cannabidiol (1)
- cannabinoids (1)
- cannabis (1)
- capsaicin (1)
- carbapenem resistance (1)
- carbapenemase (1)
- carcinoma (1)
- cardiac (1)
- cardiac I/R injury (1)
- cardiac ischaemia‐reperfusion (1)
- cardiac magnetic (1)
- cardiac rehabilitation (1)
- cardiomyopathy (1)
- cardiothoracic surgery (1)
- career promotion (1)
- cartilage oligomeric matrix protein (1)
- catheter (1)
- cell and focal adhesion (1)
- cell death (1)
- cell motility (1)
- cell proliferation (1)
- cell survival (1)
- cell-free expression (1)
- cells (1)
- cellular immunology (1)
- cellular reaction (1)
- cellular therapy (1)
- central nervous system (1)
- ceramides (1)
- cerebellum (1)
- cerumen (1)
- cervical cancer (1)
- cetuximab-bevacizumab therapy sequence (1)
- changes immune activation (1)
- chaperones (1)
- chelation therapy (1)
- chemokine receptor 4 (1)
- chemokines (1)
- chemoprotection (1)
- chemotaxis (1)
- chemotherapeutics-treated (1)
- chemotherapy (1)
- chest trauma (1)
- children and adolescents (1)
- chloroplasts (1)
- cholestasis (1)
- cholesterol (1)
- cholinesterase (1)
- chronic coronary artery disease (1)
- chronic illness (1)
- chronic inflammation (1)
- chronic kidney disease (1)
- chronic liver disease (1)
- chronic low back pain (1)
- chronic metabolic acidosis (1)
- chronic myeloid leukemia (1)
- chronic thromboembolic pulmonary hypertension (1)
- chronic total occlusion (1)
- chronische Niereninsuffizienz (1)
- chronische metabolische Azidose (1)
- circulation (1)
- cisplatin resistance (1)
- cisplatin sensitivity (1)
- classical Hodgkin lymphoma (1)
- clinical (1)
- clinical benefit (1)
- clinical history (1)
- clinical immunology (1)
- clinical pathways (1)
- clinical study (1)
- clinically important restrictions and symptoms (1)
- cloacal malformation (1)
- clock genes (1)
- clopidogrel (1)
- clustering (1)
- co-crystallization (1)
- coagulation (1)
- cochlear implant (1)
- coffee (1)
- cognitive aging (1)
- cognitive decline (1)
- coherence (1)
- collagen type I (1)
- collagen-based matrix (1)
- collateral growth (1)
- colon carcinoma (1)
- colorectal cancer (1)
- colorectal cancer (CRC) (1)
- combined therapy (1)
- common genetic variation (1)
- common variants (1)
- comparative oncology (1)
- comparative pathology (1)
- competition fear (1)
- complement; patients (1)
- complex IV (1)
- computational biology (1)
- computational neuroimaging (1)
- computed tomography (1)
- computer vision (1)
- computer-aided diagnosis (1)
- computer-assisted (1)
- conduct disorder (1)
- confidence (1)
- consolidation treatment (1)
- contact heat evoked potentials (CHEPS) (1)
- contamination (1)
- contralateral delay activity (1)
- coping (1)
- coronary artery bypass surgery (1)
- coronary artery disease (1)
- coronavirus disease 2019 (1)
- cortex (1)
- cortex, gray matter (1)
- cortical folding (1)
- cortisol (1)
- cost-of-illness (1)
- covalent drugs (1)
- covalent inhibitors (1)
- cranberry (1)
- crepitation (1)
- crepitus (1)
- critical care (1)
- cross fitness (1)
- cryogenic electron microscopy (1)
- cyclin Y (1)
- cyclooxygenase 2 (1)
- cyclophosphamide (1)
- cytarabin (1)
- cytokine gene expression (1)
- cytokine storm (1)
- cytokine-induced killer cells (1)
- cytotoxic lymphocytes (1)
- dapagliflozin (1)
- data projection (1)
- day clinic (1)
- debris (1)
- decision making (1)
- decision support systems (1)
- decision-making (1)
- declaration of tobacco ingredients (1)
- decorin (1)
- deep fascia (1)
- deep mutational scanning (1)
- deep sedation (1)
- deferred treatment (1)
- delayed auditory feedback (1)
- delayed treatment (1)
- demineralized bone matrix (1)
- dendritic cells (1)
- dental assistants (1)
- dental emergency treatment (1)
- dentin adhesives (1)
- dentist (1)
- dentistry (1)
- dentists (1)
- depressive symptoms clusters (1)
- detoxification (1)
- deubiquitinating enzyme (1)
- development (1)
- diabetes (1)
- diabetes therapy (1)
- diagnosis (1)
- diagnostic algorithm (1)
- diagnostic test (1)
- diet (1)
- differential scanning fluorimetry (1)
- differentiation (1)
- diffusion tensor imaging (1)
- digital pathology (1)
- dihydroceramide (1)
- disease modelling (1)
- disease models (1)
- dislocation (1)
- distress (1)
- diuretics (1)
- docking studies (1)
- dog study (1)
- donor safety (1)
- drug abstinence (1)
- drug delivery (1)
- drug‐resistant epilepsy (1)
- drug–drug interaction (DDI) (1)
- dual BET/HDAC inhibitor (1)
- dual antiplatelet therapy (1)
- dysbiosis (1)
- dysferlin (1)
- dysferlinopathy (1)
- dysphagia (1)
- e-Health (1)
- e-health (1)
- e-scooter (1)
- eHealth (1)
- early detection (1)
- early myocardial damage (EMD) (1)
- early recognition (1)
- economic burden (1)
- effect mechanism (1)
- effectiveness (1)
- efficacy (1)
- effort (1)
- eight disorders (1)
- elderly patients (1)
- electric scooter (1)
- electroencephalography (EEG), EEG reference choices, event-related potentials (ERP), independent component analysis (ICA), pain research, contact heat evoked potentials (CHEPS) (1)
- electrolytic cleaning (1)
- electromyostimulation (1)
- electron transport chain (1)
- electronic adherence measurement (1)
- electrophilic fatty acids (1)
- elimination rate constant (1)
- embolization (1)
- emergence (1)
- empagliflozin (1)
- encoding (1)
- end of life care (1)
- endocannabinoids (1)
- endolysosomal system (1)
- endometrial cancer (1)
- endothelial cells (1)
- engagement (1)
- enterovirus (1)
- eph receptor tyrosin kinase family (1)
- ephrins (1)
- epidemics (1)
- epidemiology (1)
- epidermal growth factor receptor (1)
- epididymitis (1)
- epigenetic (1)
- epigenetics (1)
- epileptic encephalopathy (1)
- episodic memory (1)
- epithelial cells (1)
- epithelial-to-mesenchymal transition (EMT) (1)
- epithelial‐mesenchymal transition (1)
- epitope mapping (1)
- erectile dysfunction (1)
- ergonomics (1)
- erythropoietin (EPO) (1)
- escape mutations (1)
- essential tremor (1)
- ethyl pyruvate (1)
- euthymic (1)
- event logs (1)
- event-related potentials (1)
- event-related potentials (ERP) (1)
- everolimus (1)
- ex vivo model (1)
- ex-Gaussian analysis (1)
- executive function (1)
- exercise on prescription (1)
- exercise therapy (1)
- exercise treatment (1)
- exertion (1)
- experimental human pain models (1)
- experimental pain models (1)
- expertise (1)
- exposure (1)
- extensively drug-resistant (1)
- external fixation (1)
- external joint moments (1)
- extracellular matrix (1)
- extraction socket healing (1)
- extraversion (1)
- extremity (1)
- eye-tracking (1)
- fMRI (1)
- fMRT (1)
- face inversion effect (1)
- facial nerve functional outcome (1)
- factor VIII (FVIII) (1)
- familial infantile epilepsy (1)
- fasting (1)
- fatigue (1)
- feeder cells (1)
- femoral artery ligation (1)
- fenfluramine (1)
- ferric carboxymaltose (1)
- fibromodulin (1)
- fingolimod (1)
- fixation (1)
- focal cortical dysplasia (1)
- focal seizures (1)
- force transmission (1)
- formalin-fixed paraffin-embedded (FFPE) samples (1)
- fourth (1)
- fractional anisotropy (1)
- fractionation (1)
- fracture (1)
- fragile-X-associated tremor-ataxia syndrome (1)
- fragment-based design (1)
- fragment-based drug design (1)
- free gingival graft (1)
- frontal cortex (1)
- fronto-temporal lobar dementia (1)
- fronto-temporal-lobar-dementia (1)
- fully human (1)
- fumonisin B1 (1)
- functional connectivity (1)
- functional coupling (1)
- functional genetics (1)
- functional imaging (1)
- fundoplication (1)
- furcation involvement (1)
- further education (1)
- fusion (1)
- gap junction protein alpha 4-genotype (1)
- gas chromatography-mass spectrometry (1)
- gastric surgery (1)
- gastrocnemius (1)
- gastroesophageal reflux (1)
- gender (1)
- gender difference (1)
- gene regulation (1)
- gene therapy (1)
- genetic diversity (1)
- genetic generalized epilepsy (1)
- genetic phenotypes (1)
- genetic polymorphisms (1)
- genetic predisposition (1)
- genome-wide association study (1)
- geriatric patients (1)
- geriatrischer Ultraschall (1)
- germ cell tumors (1)
- glioblastoma cells (1)
- glucose (1)
- glucose metabolism (1)
- glycosaminoglycan (1)
- graft (1)
- graph theory (1)
- grey matter volume (1)
- growth inhibition (1)
- gyrification (1)
- haematologic malignancies (1)
- haemophilia A (1)
- haemophilic arthropathy (1)
- haemostasis (1)
- harmine (1)
- health care (1)
- health-related quality of life (1)
- healthcare workers (1)
- healthy subjects (1)
- hearing nerve (1)
- heat stress (1)
- hemadsorption (1)
- hematoma (1)
- hematopoietic stem and progenitor cells (1)
- heme-regulated inhibitory kinase (1)
- hemiplegic migraine (1)
- hemispherotomy (1)
- hemodynamic (1)
- hemodynamic instability (1)
- hemophilia A (1)
- hemorrhage (1)
- hemorrhagic transformation (1)
- hepatic fibrosis (1)
- hepatic stellate cells (1)
- hepatitis C virus (1)
- hepatitis C virus (HCV) (1)
- hepatitis E (1)
- hepatocellular cancer (1)
- hepatocyte nuclear factor 4α (1)
- herb induced liver injury (1)
- hereditary angioedema (1)
- hereditary dystopic lipidosis (1)
- herpes simplex virus (1)
- hiPSC (1)
- high dimensional complex data (1)
- high surgical risk (1)
- high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (1)
- high-throughput nucleotide sequencing (1)
- high-throughput screening (1)
- higher education (1)
- high‐mobility group box‐1 (HMGB1) (1)
- hip joint (1)
- histological outcomes (1)
- histological technic (1)
- histomorphometry (1)
- histone modifications (1)
- histoplasmosis (1)
- home-based (1)
- homeostasis (1)
- hospitalization (1)
- host-pathogen interaction (1)
- huCAR19 (1)
- human decellularized dermis (1)
- human genomics (1)
- human lymph node (1)
- human sera (1)
- humanized mice (1)
- humanized mouse model (1)
- hybrid abutment (1)
- hyperarousal (1)
- hyperexcitability (1)
- hyperglycemia (1)
- hyperhomocysteinemia (1)
- hyperkalemia (1)
- hypertension (1)
- hypoglycaemia (1)
- hypophosphataemia (1)
- iDILI (1)
- iDrug induced liver injury (1)
- image-based risk modelling (1)
- imaging (1)
- immun (1)
- immune checkpoint (1)
- immune checkpoint inhibitors (1)
- immune defense (1)
- immune evasion (1)
- immune response (1)
- immuno-oncotherapy (1)
- immunoprecipitation (1)
- improvement in quality of life (1)
- in vitro (1)
- in vitro in vivo extrapolation (IVIVE) (1)
- in vitro models (1)
- in vivo model of critical size defects (1)
- independent component analysis (ICA) (1)
- indoor air pollution (1)
- induced membrane (1)
- induction chemotherapy (1)
- inertial motion capture (1)
- infant (1)
- infants (1)
- infectious diseases (1)
- inferior frontal gyrus (1)
- inflammatory bowel disease (1)
- inflammatory cytokines (1)
- inflammatory markers (1)
- inhibitors (1)
- injury (1)
- innate and adaptive immune response (1)
- inner ear therapy (1)
- inositol signaling (1)
- insomnia (1)
- instructional interventions (1)
- insulin resistance (1)
- insulitis (1)
- integrated stress response (1)
- inter-individual variability (1)
- interaction partners (1)
- interactome (1)
- interferon type III (1)
- interleukin-6 (1)
- interleukins (1)
- intervertebral disc (IVD) (1)
- intrinsic drug resistance (1)
- invasion (1)
- invasive mold infection (1)
- inverse dynamics (1)
- investigational (1)
- inflammation (1)
- iron deficiency (1)
- iron overload versus deprivation (1)
- iron supplements (1)
- irradiation (1)
- ischaemia (1)
- isolation (1)
- joint bleeding (1)
- joint loading (1)
- joint moments (1)
- juvenile brain lesion (1)
- kaatsu training (1)
- kallikrein inhibitor (1)
- keratinized mucosa (1)
- ketogenic (1)
- ketone body (1)
- kidney formation (1)
- kidney function (1)
- kinase inhibitors (1)
- kinetic fingerprint (1)
- knee adduction moment (1)
- knee joint (1)
- knee noise (1)
- knee sound (1)
- knockout (1)
- kynureninase (1)
- kynurenine (1)
- lacosamide (1)
- lactate (1)
- lamotrigine (1)
- latent class analysis (1)
- left ventricular non-compaction (1)
- left ventricular trabeculation (1)
- leg alignment (1)
- lentiviral vector (1)
- leukocytes (1)
- leukopenia (1)
- levetiracetam (1)
- lichen extracts (1)
- light microscopy (1)
- limb girdle muscular dystrophy type 2B (LGMD2B) (1)
- lipid (1)
- lipid raft (1)
- lipidomic analysis (1)
- lipocalin-2 (1)
- lipoxin A4 (1)
- liquid PRF (1)
- liquid chromatography–mass spectrometry (1)
- liver fibrosis (1)
- liver transplantation (1)
- liver transplantation center (1)
- local inflammation (1)
- local-field potentials (1)
- locus coeruleus (1)
- long reads (1)
- long-term outcome (1)
- long-term potentiation (1)
- long-term prophylaxis (1)
- long-term success (1)
- long-term survival (1)
- longevity (1)
- longitudinal follow-up after epilepsy surgery (1)
- loss (1)
- low doses (1)
- low-density lipoprotein cholesterol (1)
- low-risk (1)
- lower extremity arterial disease (1)
- lumbago (1)
- lumbalgia (1)
- lumbar spinal canal stenosis (1)
- lumican (1)
- lung disease phenotype (1)
- lymphoma (1)
- lysosomes (1)
- mHealth (1)
- mRNA and protein expression (1)
- macrophage polarization (1)
- magentoencephalography (MEG) (1)
- magnetic resonance imaging (1)
- magnetic resonance imaging of the brain (1)
- maintenance (1)
- major adverse cardiovascular events (1)
- major depression (MD) (1)
- major depressive disorder (MDD) (1)
- mammary carcinomas (1)
- management (1)
- mandatory reporting (1)
- maternal tobacco smoke (1)
- mathematical modeling (1)
- matrikine (1)
- matrix metalloproteinases (1)
- mean diffusivity (1)
- measurement properties (1)
- mechanism of action (1)
- mechanistic oral absorption modeling (1)
- medical training (1)
- medication adherence rate (1)
- melanoma (1)
- membrane potential (1)
- membrane repair (1)
- memory (1)
- memory and learning tests (1)
- mental distress (1)
- mesenchymal stem cell (1)
- mesenchymal stromal/stem cells (1)
- meta-analysis (1)
- metabolic reprogramming (1)
- metabolic syndrome (1)
- metabolism (1)
- miR-142-3p (1)
- miR-181 (1)
- miR-6862-5p (1)
- mice (1)
- micro CT (1)
- microdialysis (1)
- microlesions (1)
- microsurgical treatment (1)
- mid-IR spectroscopy (1)
- migration and invasion (1)
- mini gastric bypass (1)
- minimal clinically important difference (1)
- minimal residual disease (1)
- mir-148a (1)
- mitochondrial antiviral signaling protein (MAVS) (1)
- mitochondrial dysfunction (1)
- mitochondrial metabolism (1)
- mitochondrial morphology (1)
- mitochondrial respiration (1)
- mixed lineage kinase domain-like (1)
- model psychosis (1)
- molecular adaptation (1)
- molecular biology (1)
- molecular dynamics (1)
- molecular switch (1)
- molecular tumor board (1)
- molecular typing (1)
- monoamine oxidase A (1)
- monocyte chemotactic protein 1 (MCP-1) (1)
- mononuclear cell (1)
- monotype abutment (1)
- monsoon (1)
- morphogenesis (1)
- morphological filtering (1)
- morphometry (1)
- mortality (1)
- mortality analysis (1)
- mortality risk (1)
- motivation (1)
- motor control exercise (1)
- mouse (1)
- mouse model (1)
- mouse models (1)
- movement pattern (1)
- movement profile (1)
- multi-network (1)
- multi-task learning (1)
- multimodal complex treatment (1)
- multimorbidity (1)
- multiple trauma (1)
- multitarget drugs (1)
- murine model (1)
- muscle (1)
- muscle disease (1)
- muscular dystrophy (1)
- musculoskeletal (1)
- musculoskeletal inflammation (1)
- musculoskeletal pain (1)
- musculoskeletal radiographs (1)
- mutational antigenic profiling (1)
- myocardial perfusion (1)
- myofascial (1)
- myofascial chains (1)
- myofascial force transmission (1)
- myoferlin (1)
- myotonia congenita (1)
- nanobodies (1)
- nanodiscs (1)
- narrative content analysis (1)
- narrative economics (1)
- narrative medicine (1)
- natriuretic peptide (1)
- natural cytotoxicity (1)
- natural killer cell (1)
- naturalistic sample (1)
- necrosis (1)
- neglect (1)
- negligencia (1)
- neonate (1)
- neonates (1)
- neonatology (1)
- neoplasms (1)
- nerve (1)
- nerve injury (1)
- networks (1)
- neurexin (1)
- neurogenesis (1)
- neurological impairment (1)
- neuronal maturation (1)
- neuropathic pain (1)
- neuropathy (1)
- neurophysiology (1)
- neuropsychology (1)
- neuroticism (1)
- neurovascular bundle preservation (1)
- neutralization (1)
- neutralizing antibodies (1)
- newborn (1)
- newborn screening (1)
- next-generation sequencing (1)
- nitroalkylation (1)
- niños (1)
- non-coding RNAs (1)
- non-malignant hematological diseases (1)
- noninterventional (1)
- noninvasive blood glucose analysis (1)
- nonspecific (1)
- non‐selective beta‐blocker (1)
- nuclear receptor (1)
- nucleotide analogue (1)
- nucleotide metabolism (1)
- nutrient endocytosis (1)
- observational study (1)
- occupational health (1)
- off-pump surgery (1)
- oncogenic signaling (1)
- oncological gastrectomy (1)
- oncological outcome (1)
- one anastomosis gastric bypass (1)
- online information processing (1)
- online reasoning patterns (1)
- online survey (1)
- operative (1)
- optical coherence tomography (1)
- orientation (1)
- orthopaedic patients (1)
- oscillations (1)
- osteoarthritis (1)
- osteogenic sarcoma cells (1)
- osteoimmunological changes (1)
- otoferlin (1)
- ouabain (1)
- outcomes (1)
- outside-in signaling (1)
- ovary (1)
- overweight (1)
- own-face perception (1)
- oxidised lipids (1)
- pacemaker implantation (1)
- pain research (1)
- pain screening (1)
- pancreatic ductal adenocarcinoma (1)
- pancreatic surgery (1)
- parkinson’s disease (1)
- passive immunization (1)
- passive smoke (1)
- patient centered care (1)
- patient preferences (1)
- patient questionnaire (1)
- patient triage (1)
- patient-reported outcome measure (1)
- patient’s decree (1)
- patient’s perspective (1)
- paxilline (1)
- peanut allergy (1)
- pediatric (1)
- pediatric epilepsy (1)
- pediatric eye screening (1)
- pediatrics (1)
- pelvic packing (1)
- pelvic ring fracture (1)
- peptide antibiotics (1)
- peptide transport (1)
- perceptual closure (1)
- performance assessment (1)
- performance tests (1)
- peri-implantitis (1)
- pericytes (1)
- periimplantitis (1)
- perineurium (1)
- periodontal disease progression (1)
- periodontal risk assessment (1)
- periodontal risk calculator (1)
- periodontal risk factors (1)
- perioperative outcome (1)
- perioperative period (1)
- peripheral arterial disease (1)
- peri‐implantitis (1)
- peri‐implantitis therapy (1)
- person-oriented approach (1)
- personalised therapy (1)
- pet rabbit (1)
- phage (1)
- phage display (1)
- phage lysis proteins (1)
- phage therapy (1)
- pharmacogenetics (1)
- pharmacokinetics/pharmacodynamics (PK/PD) (1)
- pharmacoresistance (1)
- phenotype/genotype relation (1)
- phenotypic spectrum (1)
- phosphate (1)
- phosphorus (1)
- photothermal detection (1)
- physical activity counseling (1)
- physical training (1)
- physiologically based pharmacokinetic (PBPK) modeling (1)
- pigs (1)
- placenta (1)
- planimetric measurement (1)
- plasma (1)
- plasma-derived factor VIII concentrate, prophylaxis (1)
- plasmid (1)
- plasticity (1)
- pneumocystis (1)
- point of care (1)
- polo-like kinase 1 (1)
- poly(A)-tail (1)
- polylactide (1)
- polyomavirus (1)
- polypharmacology (1)
- polysomnography (1)
- population dynamics (1)
- portosystemic shunt (1)
- positive organizational e-interventions (1)
- post-caesarean uterus (1)
- post-exercise hypotension (1)
- post-liver transplantation management (1)
- post-traumatic (1)
- posterior fossa tumor (1)
- postmonsoon (1)
- postoperative complications (1)
- postoperative delirium (1)
- posttransnational modification (1)
- posttraumatic inflammation (1)
- posttraumatic stress disorder (1)
- ppi1 (1)
- pre-school asthma (1)
- precision weighting (1)
- prediabetes (1)
- predictive coding (1)
- preschool health examination (1)
- primary biliary cirrhosis (1)
- primary sclerosing cholangitis (1)
- proanthocyanidin (1)
- process mining (1)
- prognostic marker (1)
- prognostic value (1)
- proinflammatory microenvironment (1)
- promotion index (1)
- prophylactic vaccine (1)
- prophylaxis (1)
- proprotein convertase subtilisin/kexin type 9 inhibition (1)
- prostate volume (1)
- protease inhibitor (1)
- protein quality control (1)
- protein turnover (1)
- proteoglycan (1)
- proximal tubule (1)
- pseudokinase (1)
- psoriatic arthritis (1)
- psychischer Stress (1)
- psycho-oncology (1)
- psychology (1)
- psychosocial adjustment (1)
- public health department (1)
- public mental health (1)
- pupillometry (1)
- qRT-PCR (1)
- qRT-PCR detection (1)
- quality (1)
- quality of care (1)
- quantitative MRT (1)
- quantitative proteomics (1)
- quantitative sensory testing (1)
- quantum cascade laser (QCL) (1)
- questionnaire (1)
- radiation oncology (1)
- radical prostatectomy (1)
- radioimmunotherapy (1)
- radiomic (1)
- radiosensitization (1)
- radiotherapy (1)
- radon therapy (1)
- range of motion (1)
- rare disease (1)
- rare diseases (1)
- rare variants (1)
- rat femur critical size defect (1)
- rct (1)
- re-osseointegration (1)
- re-transplantation (1)
- reaction (1)
- reaction time (1)
- readmission rates (1)
- receptor for advanced glycation end product (RAGE) (1)
- recombinant vesicular stomatitis virus‐Zaire ebolavirus (1)
- regioisomers (1)
- regulatory T cell (1)
- regulatory T cells (1)
- regulatory T helper cells (1)
- rehabilitation (1)
- relapsing fever (1)
- relaxometry (1)
- reliable change index (1)
- remodelling (1)
- renal cell cancer (1)
- renal transplantation (1)
- renal tubular cells (1)
- renal tubular epithelial cells (1)
- repeat biopsy (1)
- repeated (1)
- reperfusion injury (1)
- repetition suppression (RS) (1)
- repetitive firing (1)
- replicative fitness (1)
- repsonse process patterns (1)
- requirements analysis (1)
- resective surgery (1)
- resistance (1)
- resistance mutation (1)
- resolution (1)
- resolution of inflammation (1)
- resonance (1)
- resting EEG (1)
- reticulocyte haemoglobin (1)
- retinal (1)
- retinoid X receptor (1)
- rhabdomyosarcoma (1)
- rheumatoid arthritis (1)
- rhodopsin (1)
- ridge preservation (1)
- right heart catheter (1)
- risk factor (1)
- risk score (1)
- rotational thromboelastometry (1)
- sCD163 (1)
- sCD206 (1)
- safety (1)
- sarcoma (1)
- sarcopenia (1)
- scanner noise (1)
- scavenger receptor (1)
- sciatic nerve (1)
- second-hand smoke (1)
- seizures (1)
- selection (1)
- selective autophagy receptor (1)
- self‐expanding (1)
- sensorimotor (1)
- sensory coding (1)
- sensory neuropathy (1)
- serine protease (NS3-4A) (1)
- serology (1)
- serum (1)
- severe acute respiratory syndrome coronavirus (1)
- severe asthma (1)
- severe congenital neutropenia (1)
- severely injured (1)
- sex (1)
- shock filter (1)
- short linear motifs (SLiMs) (1)
- shrinkage (1)
- shunt (1)
- sialitis (1)
- sickle cell anemia (1)
- signaling (1)
- skeletal muscle (1)
- sleepiness (1)
- small molecule inhibitor (1)
- smoking in pregnancy (1)
- social determinants (1)
- social isolation (1)
- socioeconomic status (1)
- soft drinks (1)
- soluble MICA (1)
- sonography (1)
- sparse imaging (1)
- spatial learning (1)
- specialized pro-resolving lipid mediators (SPMs) (1)
- specific learning disorder (1)
- sphingosine 1-phoshate (1)
- sphingosine 1-phosphate antagonistst/inhibitors (1)
- sphingosine 1-phosphate metabolism (1)
- sphingosine 1-phosphate signaling (1)
- sphingosine kinase (1)
- sphingosine-1-phosphate (1)
- spiral ganglion cells (1)
- spirochetes (1)
- spirometry (1)
- spontaneous portosystemic shunt (1)
- sports (1)
- sports performance (1)
- spreading (1)
- squamous cell carcinoma (1)
- stabilization (1)
- standardization (1)
- standardized regression-based change norms (1)
- starvation (1)
- steady-state condition (1)
- stearic acid (1)
- steatosis (1)
- stem cell transplantation (1)
- stem cells (1)
- steroid control of aging (1)
- stiripentol (1)
- strength training (1)
- streptozotocin (1)
- stress response (1)
- stretching (1)
- stromal-derived factor 1 (1)
- structural biology (1)
- structure constraints (1)
- structure–activity relationships (1)
- substance abuse disorder (1)
- suicidality (1)
- suicide (1)
- supervision (1)
- supervisión (1)
- supplementary motor area (1)
- supportive periodontal therapy (1)
- suprapubic catheter (1)
- surfactant (1)
- surgical margin (1)
- surgical procedures (1)
- swallowing (1)
- sympathicus (1)
- symptoms (1)
- synaesthesia (1)
- synaptic plasticity (1)
- synaptic scaling (1)
- synergistic interaction (1)
- synovium (1)
- synuclein (1)
- systematic biopsy (1)
- systematic scoping review (1)
- tailored treatment schedule (1)
- talent development (1)
- talent identification (1)
- targeted biopsy (1)
- targeted therapy (1)
- targeting (1)
- tauopathies (1)
- tauopathy (1)
- tea (1)
- telemedicine (1)
- tension type headache (1)
- terapia cognitivo conductual enfocada en trauma (1)
- test protocol (1)
- testis (1)
- tetrahydrocannabinol (1)
- thalassemia (1)
- therapy monitoring (1)
- therapy resistance (1)
- thiazolidine and perhydrothiazine derivatives of aldophosphamide and I-aldophosphamide (1)
- third (1)
- three-dimensional analysis (1)
- three‐dimensional analysis (1)
- thrombopenia (1)
- thrombotic microangiopathy (1)
- thrombotic thrombocytopenic purpura (1)
- tick (1)
- time-lapse imaging (1)
- tissue slice co-cultures (1)
- tobacco control (1)
- tobacco products (1)
- toc64 (1)
- tooth (1)
- tooth autotransplantation (1)
- tooth loss (1)
- tooth transplantation (1)
- total hip replacement (1)
- tracking (1)
- traditional Chinese medicine (1)
- traffic accident (1)
- trafficking (1)
- training effects (1)
- transcatheter aortic valve replacement (TAVR) (1)
- transcatheter aortic valve replacement (TAVR), aortic valve stenosis (AS) (1)
- transcriptomics (1)
- transferrin (1)
- transforming growth factor-β (1)
- transfusion (1)
- transgenically augmented CAR NK cell (1)
- transjugular intrahepatic portosystemic shunt (TIPS) (1)
- transjugular portosystemic intrahepatic (1)
- translational medical research (1)
- translational medicine (1)
- translational reseach (1)
- translatome (1)
- translocon (1)
- transmission routes (1)
- transportation (1)
- transrectal prostate biopsy (1)
- transurethral catheter (1)
- transverse axis (1)
- trauma (1)
- trauma registry (1)
- traumafocused cognitive behavioural therapy (1)
- traumatic brain injury (1)
- traumatic brain injury (TBI) (1)
- traumaticbraininjury(TBI) (1)
- treatment-related changes (1)
- trigeminal pain (1)
- trophoblast (1)
- tryptophan (1)
- tumor adhesion (1)
- tumor angiogenesis (1)
- tumor hypoxia (1)
- tumor infiltrating lymphocytes (1)
- tumor invasion (1)
- tumor migration (1)
- tumor pain (1)
- tumor perfusion (1)
- tumor stroma (1)
- tumor xenograft (1)
- tumor-associated macrophages (1)
- type 1 diabetes (1)
- type 2 diabetes (1)
- type-1-diabetes (1)
- tyrosinase inhibitor (1)
- tyrosine kinase inhibitor (1)
- tyrosine kinase inhibitors (1)
- tyrosine kinase inhibitors. (1)
- tyrosine kinase receptor signaling (1)
- ubiquitin (1)
- ubiquitin hydrolase (1)
- ubiquitin receptor (1)
- ultrasonic cleaning (1)
- ultrasound (1)
- unanticipated (1)
- unconventional T cell (1)
- unilateral hip osteoarthritis (1)
- unspecific low back pain (1)
- urethral stricture (1)
- urethroplasty (1)
- urinary tract development (1)
- uterine wall (1)
- vaccination (1)
- vacuuming (1)
- valproic acid (1)
- value frameworks (1)
- variability (1)
- variable silent delay (1)
- vascular endothelial growth factor receptor (1)
- vascular surgery (1)
- vector (1)
- venous occlusion (1)
- ventralis intermedius nucleus (1)
- venturesomeness (1)
- vertical transmission (1)
- vestibular schwannoma (1)
- vibroarthrographic (1)
- vigilance (1)
- vincristine (1)
- viral infection (1)
- viruses (1)
- vision (1)
- visual attention (1)
- visual priming (1)
- vitamin B deficiency (1)
- vitamin B12 (1)
- vitamin D (1)
- vitamin D deficiency (1)
- vitamin D metabolites (1)
- vitamin k antagonists (1)
- volatile sedation (1)
- von Willebrand diseases (1)
- waiting time (1)
- walking (1)
- weakly supervised learning (1)
- weight loss (1)
- wheezing (1)
- white matter hyperintensity (1)
- whole abdominal radiotherapy (1)
- whole genome sequencing (1)
- whole slide image (1)
- working memory (1)
- workplace health promotion (1)
- xenograft (1)
- yellow flags (1)
- youth football (1)
- zebrafish development (1)
- Öffentlichkeit (1)
- Übertragungswege (1)
- ΔNp63 (1)
- α-amylase inhibitor (1)
- α-particles (1)
- γ‐H2AX (1)
- fibrogenesis (1)
- fingolimod (1)
Institute
- Medizin (732)
- Biochemie, Chemie und Pharmazie (41)
- Biowissenschaften (22)
- Frankfurt Institute for Advanced Studies (FIAS) (21)
- Sportwissenschaften (21)
- MPI für Hirnforschung (14)
- Präsidium (14)
- Biochemie und Chemie (11)
- Psychologie und Sportwissenschaften (11)
- Ernst Strüngmann Institut (9)
Background: To assess late toxicity, quality of life and oncological outcome after consolidative whole abdominal radiotherapy (WART) following cytoreductive surgery and carboplatin/paclitaxel chemotherapy in high risk patients with advanced ovarian cancer FIGO stage III using IMRT (Intensity modulated radiation therapy).
Methods: The OVAR-IMRT-02 study is a multi-center single-arm phase-II-trial. Twenty patients with optimally debulked ovarian cancer stage FIGO III with complete remission after chemotherapy were treated with intensity modulated WART. A total dose of 30 Gy in 20 fractions was applied to the entire peritoneal cavity. Primary endpoint was treatment tolerability; secondary objectives were acute and chronic toxicities, quality of life, rates of therapy disruption/abortion, progression-free survival (PFS) and overall survival (OS).
Results: All patients completed treatment and 10/20 patients (50%) reached the final study follow-up of 36 months. Late side effects consisted of °1-°2 lower limb edema (44.5%), with one patient (5.6%) showing °3 edema. Three patients (16.7%) showed elevated gamma-Glutamyltransferase. There were no severe late side effects regarding
renal or hepatic function or any gastrointestinal toxicity greater than °2. During WART, mean global health status
decreased by 18.1 points (95%-CI: 7.1–29.0), but completely normalized after 6 months. The same trend was observed for the function scale scores. Kaplan-Meier-estimated 1-, 2- and 3-year PFS was 74, 51 and 40%, respectively. 1-, 2- and 3-year OS was 89, 83 and 83%, respectively.
Conclusions: Intensity modulated WART after aggressive surgery and carboplatin/paclitaxel chemotherapy is associated with an acceptable risk of acute and late toxicity and minor impact on long-term quality of life. Together
with the promising results for PFS and OS, intensity modulated WART could offer a new therapeutic option for consolidation treatment of patients with advanced ovarian cancer.
Trial registration: The study is registered with ClinicalTrials.gov (NCT01180504). Registered 12 August 2010 – retrospectively registered.
Despite the great success of antiretroviral therapy, both in the treatment and prevention of HIV-1 infection, a vaccine is still urgently needed to end the epidemic. According to UNAIDS, in 2018, about 35% of HIV-1 infected persons did not receive antiretroviral therapy (ART), resulting in 1.7 million new infections in that year...
Purpose: Diffuse cortical damage in relapsing–remitting multiple sclerosis (RRMS) is clinically relevant but cannot be directly assessed with conventional MRI. In this study, it was aimed to use diffusion tensor imaging (DTI) techniques with optimized intrinsic eddy current compensation to quantify and characterize cortical mean diffusivity (MD) and fractional anisotropy (FA) changes in RRMS and to analyze the distribution of these changes across the cortex.
Materials and Methods: Three-Tesla MRI acquisition, mapping of the MD providing information about the integrity of microstructural barriers and of the FA reflecting axonal density and surface-based analysis with Freesurfer were performed for 24 RRMS patients and 25 control subjects.
Results: Across the whole cortex, MD was increased in patients (p < 0.001), while surface-based analysis revealed focal cortical FA decreases. MD and FA changes were distributed inhomogeneously across the cortex, the MD increase being more widespread than the FA decrease. Cortical MD correlated with the Expanded Disability Status Scale (EDSS, r = 0.38, p = 0.03).
Conclusion: Damage of microstructural barriers occurs inhomogeneously across the cortex in RRMS and might be spatially more widespread than axonal degeneration. The results and, in particular, the correlation with the clinical status indicate that DTI might be a promising technique for the monitoring of cortical damage under treatment in larger clinical studies.
Experiments in cadavers have demonstrated significant mechanical interactions between constituents of myofascial chains. However, evidence for such force transmission effects is scarce under in vivo conditions. The purpose of this trial was to examine the impact of ankle motion on soft tissue displacement of the dorsal thigh. Eleven healthy active individuals (26.8 ± 4.3 years, six males), in prone position and with the knee extended, underwent passive calf stretches (ankle dorsal extension) imposed by an isokinetic dynamometer. High-resolution ultrasound was used to simultaneously capture the displacement of the semimembranosus muscle, which was quantified by means of cross-correlation analysis. Inactivity of the leg muscles was controlled using surface electromyography (EMG). One participant had to be excluded due to major EMG activity during the experiment. According to a one-sample t test testing the difference to the neutral zero position, ankle dorsal extension induced substantial caudal muscle displacements (5.76 ± 2.67 mm, p < 0.0001). Correlation analysis (Spearman), furthermore, revealed a strong association between maximal dorsal extension and semimembranosus motion (rho = 0.76, p = 0.02). In conclusion, the present trial provides initial in vivo evidence for a mechanical force transmission between serially connected skeletal muscles. This means that local alterations of the mechanical tissue properties may modify flexibility in neighboring (superior or inferior) joints.
The quantified behavioral test - a confirmatory test in the diagnostic process of adult ADHD?
(2020)
The differential diagnosis of attention deficit hyperactivity disorder (ADHD) in adulthood is complicated by comorbid disorders, but also by the overlapping of main symptoms such as inattentiveness, impulsivity, and hyperactivity with other disorders. Neuropsychological tests like continuous performance tests (CPT) try to solve this dilemma by objectively measurable parameters. We investigated in a cohort of n=114 patients presenting to an ADHD outpatient clinic how well a commercially available CPT test (QbTest®) can differentiate between patients with ADHD (n=94) and patients with a disconfirmed ADHD diagnosis (n=20). Both groups showed numerous comorbidities, predominantly depression (27.2% in the ADHD group vs. 45% in the non-ADHD group) and substance-use disorders (18.1% vs. 10%, respectively). Patients with ADHD showed significant higher activity (2.07 ± 1.23) than patients without ADHD (1.34 ± 1.27, dF=112; p=0.019), whereas for the other core parameters, inattention and impulsivity no differences could be found. Reaction time variability has been discussed as a typical marker for inattention in ADHD. Therefore, we investigated how well ex-Gaussian analysis of response time can differentiate between ADHD and other patients, showing, that it does not help to identify patients with ADHD. Even though patients with ADHD showed significantly higher activity, this parameter differed only poorly between patients (accuracy AUC 65% of an ROC-Curve). We conclude that CPTs do not help to identify patients with ADHD in a specialized outpatient clinic. The usability of this test for differentiating between ADHD and other psychiatric disorders is poor and a sophisticated analysis of reaction time did not decisively increase the test accuracy.
Evidence gained from recent studies has generated increasing interest in the role of vitamin D in extraskeletal functions such as inflammation and immunoregulation. Although vitamin D deficiency has been implicated in the pathophysiology of inflammatory diseases including inflammatory bowel disease (IBD), evidence as to whether vitamin D supplementation may cure or prevent chronic disease is inconsistent. Since 25OH-vitamin D (25OHD) has been suggested to be an acute-phase protein, its utility as a vitamin D status marker is therefore questionable. In this study, possible interactions of vitamin D and inflammation were studied in 188 patients with IBD, with high-sensitivity C-reactive protein (hsCRP) levels ≥ 5 mg/dL and/or fecal calprotectin ≥ 250 µg/g defined as biochemical evidence of inflammatory activity. Levels of 25OHD and vitamin D-binding protein (VDBP) were determined by ELISA, and 1,25-dihydroxyvitamin D (1,25OHD) and dihydroxycholecalciferol (24,25OHD) by LC-MS/MS. Free and bioavailable vitamin D levels were calculated with the validated formula of Bikle. Serum 1,25OH2D and vitamin D binding protein (VDBP) levels were shown to differ between the inflammatory and noninflammatory groups: patients with inflammatory disease activity had significantly higher serum concentrations of 1,25OH2D (35.0 (16.4–67.3) vs. 18.5 (1.2–51.0) pg/mL, p < 0.001) and VDBP (351.2 (252.2–530.6) vs. 330.8 (183.5–560.3) mg/dL, p < 0.05) than patients without active inflammation. Serum 24,25OH2D levels were negatively correlated with erythrocyte sedimentation rate (ESR) (−0.155, p = 0.049) while concentrations of serum 1,25OH2D correlated positively with hsCRP (0.157, p = 0.036). Correlations with serum VDBP levels were found for ESR (0.150, p = 0.049), transferrin (0.160, p = 0.037) and hsCRP (0.261, p < 0.001). Levels of serum free and bioavailable 25OHD showed a negative correlation with ESR (−0.165, p = 0.031, −0.205, p < 0.001, respectively) and hsCRP (−0.164, p = 0.032, −0.208, p < 0.001 respectively), and a moderate negative correlation with fecal calprotectin (−0.377, p = 0.028, −0.409, p < 0.016, respectively). Serum total 25OHD concentration was the only vitamin D parameter found to have no specific correlation with any of the inflammatory markers. According to these results, the traditional parameter, total 25OHD, still appears to be the best marker of vitamin D status in patients with inflammatory bowel disease regardless of the presence of inflammation.
Macrophage and tumor cell cross-talk is fundamental for lung tumor progression: we need to talk
(2020)
Regardless of the promising results of certain immune checkpoint blockers, current immunotherapeutics have met a bottleneck concerning response rate, toxicity, and resistance in lung cancer patients. Accumulating evidence forecasts that the crosstalk between tumor and immune cells takes center stage in cancer development by modulating tumor malignancy, immune cell infiltration, and immune evasion in the tumor microenvironment (TME). Cytokines and chemokines secreted by this crosstalk play a major role in cancer development, progression, and therapeutic management. An increased infiltration of Tumor-associated macrophages (TAMs) was observed in most of the human cancers, including lung cancer. In this review, we emphasize the role of cytokines and chemokines in TAM-tumor cell crosstalk in the lung TME. Given the role of cytokines and chemokines in immunomodulation, we propose that TAM-derived cytokines and chemokines govern the cancer-promoting immune responses in the TME and offer a new immunotherapeutic option for lung cancer treatment.
BAG3, a multifunctional HSP70 co-chaperone and anti-apoptotic protein that interacts with the ATPase domain of HSP70 through its C-terminal BAG domain plays a key physiological role in cellular proteostasis. The HSP70/BAG3 complex determines the levels of a large number of selective client proteins by regulating their turnover via the two major protein degradation pathways, i.e. proteasomal degradation and macroautophagy. On the one hand, BAG3 competes with BAG1 for binding to HSP70, thereby preventing the proteasomal degradation of its client proteins. By functionally interacting with HSP70 and LC3, BAG3 also delivers polyubiquitinated proteins to the autophagy pathway. BAG3 exerts a number of key physiological functions, including an involvement in cellular stress responses, proteostasis, cell death regulation, development, and cytoskeletal dynamics. Conversely, aberrant BAG3 function/expression has pathophysiological relevance correlated to cardiomyopathies, neurodegeneration, and cancer. Evidence obtained in recent years underscores the fact that BAG3 drives several key hallmarks of cancer, including cell adhesion, metastasis, angiogenesis, enhanced autophagic activity, and apoptosis inhibition. This review provides a state-of-the-art overview on the role of BAG3 in stress and therapy resistance of cancer, with a particular focus on BAG3-dependent modulation of apoptotic signaling and autophagic/lysosomal activity.
Cancer-induced pain occurs frequently in patients when tumors or their metastases grow in the proximity of nerves. Although this cancer-induced pain states poses an important therapeutical problem, the underlying pathomechanisms are not understood. Here, we implanted adenocarcinoma, fibrosarcoma and melanoma tumor cells in proximity of the sciatic nerve. All three tumor types caused mechanical hypersensitivity, thermal hyposensitivity and neuronal damage. Surprisingly the onset of the hypersensitivity was independent of physical contact of the nerve with the tumors and did not depend on infiltration of cancer cells in the sciatic nerve. However, macrophages and dendritic cells appeared on the outside of the sciatic nerves with the onset of the hypersensitivity. At the same time point downregulation of perineural tight junction proteins was observed, which was later followed by the appearance of microlesions. Fitting to the changes in the epi-/perineurium, a dramatic decrease of triglycerides and acylcarnitines in the sciatic nerves as well as an altered localization and appearance of epineural adipocytes was seen. In summary, the data show an inflammation at the sciatic nerves as well as an increased perineural and epineural permeability. Thus, interventions aiming to suppress inflammatory processes at the sciatic nerve or preserving peri- and epineural integrity may present new approaches for the treatment of tumor-induced pain.
As the biology of mesenchymal stromal cells (MSCs) in patients with non-malignant hematological diseases (NMHD) is poorly understood, in the current study we performed a basic characterization of the phenotype and functional activity of NMHD-MSCs. Bone marrow (BM) of patients with thalassemia major (TM) possessed a significantly higher number of nucleated cells (BM-MNCs)/mL BM than healthy donors (P < 0.0001), which however did not result in a higher number of colony forming units-fibroblast (CFU-F) per milliliter BM. In contrast, from 1 × 106 BM-MNCs of patients with sickle cell disease (SCD) were generated significantly more CFU-Fs than from TM-BM-MNCs (P < 0.013) and control group (P < 0.02). In addition, NMHD-MSCs expressed significantly lower levels of CD146 molecule, demonstrated an equal proliferation potential and differentiated along three lineages (osteoblasts, chondrocytes and adipocytes) as healthy donors’ MSCs, with exception of TM-MSCs which differentiated weakly in adipocytes. In contrast to other NMHD-MSCs and healthy donors’ MSCs, TM-MSCs demonstrated an impaired in vitro immunosuppressive potential, either. Noteworthy, the majority of the immunosuppressive effect of NMHD-MSCs was mediated through prostaglandin-E2 (PGE2), because indomethacin (an inhibitor of PGE2 synthesis) was able to significantly reverse this effect. Our results indicate therefore that NMHD-MSCs, except TM-MSCs, may be used as an autologous cell-based therapy for post-transplant complications such as graft failure, graft-versus-host disease (GvHD) and osteonecrosis.
Accumulating evidence suggests that iron homeostasis is disturbed in tumors. We aimed at clarifying the distribution of iron in renal cell carcinoma (RCC). Considering the pivotal role of macrophages for iron homeostasis and their association with poor clinical outcome, we investigated the role of macrophage-secreted iron for tumor progression by applying a novel chelation approach. We applied flow cytometry and multiplex-immunohistochemistry to detect iron-dependent markers and analyzed iron distribution with atomic absorption spectrometry in patients diagnosed with RCC. We further analyzed the functional significance of iron by applying a novel extracellular chelator using RCC cell lines as well as patient-derived primary cells. The expression of iron-regulated genes was significantly elevated in tumors compared to adjacent healthy tissue. Iron retention was detected in tumor cells, whereas tumor-associated macrophages showed an iron-release phenotype accompanied by enhanced expression of ferroportin. We found increased iron amounts in extracellular fluids, which in turn stimulated tumor cell proliferation and migration. In vitro, macrophage-derived iron showed pro-tumor functions, whereas application of an extracellular chelator blocked these effects. Our study provides new insights in iron distribution and iron-handling in RCC. Chelators that specifically scavenge iron in the extracellular space confirmed the importance of macrophage-secreted iron in promoting tumor growth
Ferlins are multiple-C2-domain proteins involved in Ca2+-triggered membrane dynamics within the secretory, endocytic and lysosomal pathways. In bony vertebrates there are six ferlin genes encoding, in humans, dysferlin, otoferlin, myoferlin, Fer1L5 and 6 and the long noncoding RNA Fer1L4. Mutations in DYSF (dysferlin) can cause a range of muscle diseases with various clinical manifestations collectively known as dysferlinopathies, including limb-girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy. A mutation in MYOF (myoferlin) was linked to a muscular dystrophy accompanied by cardiomyopathy. Mutations in OTOF (otoferlin) can be the cause of nonsyndromic deafness DFNB9. Dysregulated expression of any human ferlin may be associated with development of cancer. This review provides a detailed description of functions of the vertebrate ferlins with a focus on muscle ferlins and discusses the mechanisms leading to disease development.
Human cytomegalovirus (CMV) is a significant cause of morbidity and mortality in patient groups at risk. We have previously shown that the anti-CMV IgG seroprevalence in an urban region of Germany has changed over the last decades. Overall, a decline from 63.7 to 57.25% had been observed between 1988–1997 and 1998–2008 (p < 0,001). Here, we continuously follow the trends to the most recent decade 2009 to 2018. In a retrospective analysis, we determined the seroprevalence of CMV IgG antibodies in our patient cohort, stratified by gender and selected groups at risk (e.g., patients with HIV infection; women of childbearing age). The overall prevalence of anti-CMV IgG non-significantly declined further from 57.25% in 1998–2008 to 56.48% in 2009–2018 (p = 0.881). Looking at gender differences, overall CMV seroprevalence in males declined to 52.82% (from 55.54% in 1998–2008; p = 0.0254), while it non-significantly increased in females to 59.80%. The high seroprevalence in patients with a known HIV infection further increased from 87.46% in 1998–2008 to 92.93% in the current period (p = 0.9999). In women of childbearing age, no significant changes over the last three decades could be observed. The CMV seroprevalence in oncological patients was determined to be 60.64%. Overall, the former significant decline of CMV seroprevalence between the decades 1988–1997 and 1998–2008 in this urban region of Germany slowed down to a non-significant decrease of 0.77% (1998–2008 vs. 2009–2018). This might be an indicator that CMV seroprevalence has reached a plateau.
Background: The vascular effects of training under blood flow restriction (BFR) in healthy persons can serve as a model for the exercise mechanism in lower extremity arterial disease (LEAD) patients. Both mechanisms are, inter alia, characterized by lower blood flow in the lower limbs. We aimed to describe and compare the underlying mechanism of exercise-induced effects of disease- and external application-BFR methods. Methods: We completed a narrative focus review after systematic literature research. We included only studies on healthy participants or those with LEAD. Both male and female adults were considered eligible. The target intervention was exercise with a reduced blood flow due to disease or external application. Results: We identified 416 publications. After the application of inclusion and exclusion criteria, 39 manuscripts were included in the vascular adaption part. Major mechanisms involving exercise-mediated benefits in treating LEAD included: inflammatory processes suppression, proinflammatory immune cells, improvement of endothelial function, remodeling of skeletal muscle, and additional vascularization (arteriogenesis). Mechanisms resulting from external BFR application included: increased release of anabolic growth factors, stimulated muscle protein synthesis, higher concentrations of heat shock proteins and nitric oxide synthase, lower levels in myostatin, and stimulation of S6K1. Conclusions: A main difference between the two comparators is the venous blood return, which is restricted in BFR but not in LEAD. Major similarities include the overall ischemic situation, the changes in microRNA (miRNA) expression, and the increased production of NOS with their associated arteriogenesis after training with BFR.
Background: Obesity and depression are both associated with changes in sleep/wake regulation, with potential implications for individualized treatment especially in comorbid individuals suffering from both. However, the associations between obesity, depression, and subjective, questionnaire-based and objective, EEG-based measurements of sleepiness used to assess disturbed sleep/wake regulation in clinical practice are not well known.
Objectives: The study investigates associations between sleep/wake regulation measures based on self-reported subjective questionnaires and EEG-derived measurements of sleep/wake regulation patterns with depression and obesity and how/whether depression and/or obesity affect associations between such self-reported subjective questionnaires and EEG-derived measurements.
Methods: Healthy controls (HC, NHC = 66), normal-weighted depressed (DEP, NDEP = 16), non-depressed obese (OB, NOB = 68), and obese depressed patients (OBDEP, NOBDEP = 43) were included from the OBDEP (Obesity and Depression, University Leipzig, Germany) study. All subjects completed standardized questionnaires related to daytime sleepiness (ESS), sleep quality and sleep duration once as well as questionnaires related to situational sleepiness (KSS, SSS, VAS) before and after a 20 min resting state EEG in eyes-closed condition. EEG-based measurements of objective sleepiness were extracted by the VIGALL algorithm. Associations of subjective sleepiness with objective sleepiness and moderating effects of obesity, depression, and additional confounders were investigated by correlation analyses and regression analyses.
Results: Depressed and non-depressed subgroups differed significantly in most subjective sleepiness measures, while obese and non-obese subgroups only differed significantly in few. Objective sleepiness measures did not differ significantly between the subgroups. Moderating effects of obesity and/or depression on the associations between subjective and objective measures of sleepiness were rarely significant, but associations between subjective and objective measures of sleepiness in the depressed subgroup were systematically weaker when patients comorbidly suffered from obesity than when they did not.
Conclusion: This study provides some evidence that both depression and obesity can affect the association between objective and subjective sleepiness. If confirmed, this insight may have implications for individualized diagnosis and treatment approaches in comorbid depression and obesity.
With increasing distribution of endovascular stroke therapies, transient middle cerebral artery occlusion (tMCAO) in mice now more than ever depicts a relevant patient population with recanalized M1 occlusion. In this case, the desired therapeutic effect of blood flow restauration is accompanied by breakdown of the blood-brain barrier (BBB) and secondary reperfusion injury. The aim of this study was to elucidate short and intermediate-term transcriptional patterns and the involved pathways covering the different cellular players at the neurovascular unit after transient large vessel occlusion. To achieve this, male C57Bl/6J mice were treated according to an intensive post-stroke care protocol after 60 min occlusion of the middle cerebral artery or sham surgery to allow a high survival rate. After 24 h or 7 days, RNA from microvessel fragments from the ipsilateral and the contralateral hemispheres was isolated and used for mRNA sequencing. Bioinformatic analyses allowed us to depict gene expression changes at two timepoints of neurovascular post-stroke injury and regeneration. We validated our dataset by quantitative real time PCR of BBB-associated targets with well-characterized post-stroke dynamics. Hence, this study provides a well-controlled transcriptome dataset of a translationally relevant mouse model 24 h and 7 days after stroke which might help to discover future therapeutic targets in cerebral ischemia/reperfusion injury.
Most mammals rely on the extraction of acoustic information from the environment in order to survive. However, the mechanisms that support sound representation in auditory neural networks involving sensory and association brain areas remain underexplored. In this study, we address the functional connectivity between an auditory region in frontal cortex (the frontal auditory field, FAF) and the auditory cortex (AC) in the bat Carollia perspicillata. The AC is a classic sensory area central for the processing of acoustic information. On the other hand, the FAF belongs to the frontal lobe, a brain region involved in the integration of sensory inputs, modulation of cognitive states, and in the coordination of behavioral outputs. The FAF-AC network was examined in terms of oscillatory coherence (local-field potentials, LFPs), and within an information theoretical framework linking FAF and AC spiking activity. We show that in the absence of acoustic stimulation, simultaneously recorded LFPs from FAF and AC are coherent in low frequencies (1–12 Hz). This “default” coupling was strongest in deep AC layers and was unaltered by acoustic stimulation. However, presenting auditory stimuli did trigger the emergence of coherent auditory-evoked gamma-band activity (>25 Hz) between the FAF and AC. In terms of spiking, our results suggest that FAF and AC engage in distinct coding strategies for representing artificial and natural sounds. Taken together, our findings shed light onto the neuronal coding strategies and functional coupling mechanisms that enable sound representation at the network level in the mammalian brain.
Working memory (WM) performance varies substantially among individuals but the precise contribution of different WM component processes to these functional limits remains unclear. By analyzing different types of responses in a spatial WM task, we recently demonstrated a functional dissociation between confident and not-confident errors reflecting failures of WM encoding and maintenance, respectively. Here, we use event-related brain potentials to further explore this dissociation. Healthy participants performed a delayed orientation-discrimination task and rated their response confidence for each trial. The encoding-related N2pc component was significantly reduced for confident errors compared to confident correct responses, which is indicative of an encoding failure. In contrast, the maintenance-related contra-lateral delay activity was similar for these response types indicating that in confident error trials, WM representations – potentially the wrong ones – were maintained accurately and with stability throughout the delay interval. However, contra-lateral delay activity measured during the early part of the delay period was decreased for not-confident errors, potentially reflecting compromised maintenance processes. These electrophysiological findings contribute to a refined understanding of the encoding and maintenance processes that contribute to limitations in WM performance and capacity.
Recent documentation shows that a curcumin-induced growth arrest of renal cell carcinoma (RCC) cells can be amplified by visible light. This study was designed to investigate whether this strategy may also contribute to blocking metastatic progression of RCC. Low dosed curcumin (0.2 µg/mL; 0.54 µM) was applied to A498, Caki1, or KTCTL-26 cells for 1 h, followed by exposure to visible light for 5 min (400–550 nm, 5500 lx). Adhesion to human vascular endothelial cells or immobilized collagen was then evaluated. The influence of curcumin on chemotaxis and migration was also investigated, as well as curcumin induced alterations of α and β integrin expression. Curcumin without light exposure or light exposure without curcumin induced no alterations, whereas curcumin plus light significantly inhibited RCC adhesion, migration, and chemotaxis. This was associated with a distinct reduction of α3, α5, β1, and β3 integrins in all cell lines. Separate blocking of each of these integrin subtypes led to significant modification of tumor cell adhesion and chemotactic behavior. Combining low dosed curcumin with light considerably suppressed RCC binding activity and chemotactic movement and was associated with lowered integrin α and β subtypes. Therefore, curcumin combined with visible light holds promise for inhibiting metastatic processes in RCC.
kurz und kn@pp news : Nr. 48
(2020)
Background: Patients with locally advanced bladder cancer (cT3/4 cN0/N+ cM0) have a poor prognosis despite radical surgical therapy and perioperative chemotherapy. Preliminary data suggest that the combination of radiation and immunotherapy does not lead to excess toxicity and may have synergistic (abscopal) anti-tumor effects. We hypothesize that the combined preoperative application of the PD-1 checkpoint-inhibitor Nivolumab with concomitant radiation therapy of the bladder and pelvic region followed by radical cystectomy with standardized lymphadenectomy is safe and feasible and might improve outcome for patients with locally advanced bladder cancer.
Methods: Study design: “RACE IT” (AUO AB 65/18) is an investigator initiated, prospective, multicenter, open, single arm phase II trial sponsored by Technical University Munich. Study drug and funding are provided by the company Bristol-Myers Squibb.
Study treatment: Patients will receive Nivolumab 240 mg i.v. every 2 weeks for 4 cycles preoperatively with concomitant radiation therapy of bladder and pelvic region (max. 50.4 Gy). Radical cystectomy with standardized bilateral pelvic lymphadenectomy will be performed between week 11–15.
Primary endpoint: Rate of patients with completed treatment consisting of radio-immunotherapy and radical cystectomy at the end of week 15.
Secondary endpoints: Acute and late toxicity, therapy response and survival (1 year follow up).
Main inclusion criteria: Patients with histologically confirmed, locally advanced bladder cancer (cT3/4, cN0/N+), who are ineligible for neoadjuvant, cisplatin-based chemotherapy or who refuse neoadjuvant chemotherapy.
Main exclusion criteria: Patients with metastatic disease (lymph node metastasis outside pelvis or distant metastasis) or previous chemo-, immune- or radiation therapy.
Planned sample size: 33 patients, interim analysis after 11 patients.
Background: Austria has recently been embroiled in the complex debate on the legalization of measures to end life prematurely. Empirical data on end-of-life decisions made by Austrian physicians barely exists. This study is the first in Austria aimed at finding out how physicians generally approach and make end-of-life therapy decisions.
Methods: The European end-of-life decisions (EURELD) questionnaire, translated and adapted by Schildmann et al., was used to conduct this cross-sectional postal survey. Questions on palliative care training, legal issues, and use of and satisfaction with palliative care were added. All Austrian specialists in hematology and oncology, a representative sample of doctors specialized in internal medicine, and a sample of general practitioners, were invited to participate in this anonymous postal survey.
Results: Five hundred forty-eight questionnaires (response rate: 10.4%) were evaluated. 88.3% of participants had treated a patient who had died in the previous 12 months. 23% of respondents had an additional qualification in palliative medicine. The cause of death in 53.1% of patients was cancer, and 44.8% died at home. In 86.3% of cases, pain relief and / or symptom relief had been intensified. Further treatment had been withheld by 60.0%, and an existing treatment discontinued by 49.1% of respondents. In 5 cases, the respondents had prescribed, provided or administered a drug which had resulted in death. 51.3% of physicians said they would never carry out physician-assisted suicide (PAS), while 30.3% could imagine doing so under certain conditions. 38.5% of respondents supported the current prohibition of PAS, 23.9% opposed it, and 33.2% were undecided. 52.4% of physicians felt the legal situation with respect to measures to end life prematurely was ambiguous. An additional qualification in palliative medicine had no influence on measures taken, or attitudes towards PAS.
Conclusions: The majority of doctors perform symptom control in terminally ill patients. PAS is frequently requested but rarely carried out. Attending physicians felt the legal situation was ambiguous. Physicians should therefore receive training in current legislation relating to end-of-life choices and medical decisions. The data collected in this survey will help political decision-makers provide the necessary legal framework for end-of-life medical care.
Despite the great success of antiretroviral therapy, both in the treatment and prevention of HIV-1 infection, a vaccine is still urgently needed to end the epidemic. According to UNAIDS, in 2018, about 35% of HIV-1 infected persons did not receive antiretroviral therapy (ART), resulting in 1.7 million new infections in that year. One major reason for actual HIV-1 transmissions is the fact that about 20% of HIV- 1 infected persons do not know about their HIV-positive status and therefore are not on ART despite the potential high viral load linked to high risk of virus transmission. Therefore, in particular in countries with high HIV incidence, a preventive vaccine is required to reduce HIV transmissions in the general population. In this special issue of Vaccines, invited experts contribute a series of articles to the current understanding of antibody-based HIV-1 vaccine development. ...
Objective: TGF-β2 (TGF-β, transforming growth factor beta), the less-investigated sibling of TGF-β1, is deregulated in rodent and human liver diseases. Former data from bile duct ligated and MDR2 knockout (KO) mouse models for human cholestatic liver disease suggested an involvement of TGF-β2 in biliary-derived liver diseases.
Design: As we also found upregulated TGFB2 in liver tissue of patients with primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC), we now fathomed the positive prospects of targeting TGF-β2 in early stage biliary liver disease using the MDR2-KO mice. Specifically, the influence of TgfB2 silencing on the fibrotic and inflammatory niche was analysed on molecular, cellular and tissue levels.
Results: TgfB2-induced expression of fibrotic genes in cholangiocytes and hepatic stellate cellswas detected. TgfB2 expression in MDR2-KO mice was blunted using TgfB2-directed antisense oligonucleotides (AON). Upon AON treatment, reduced collagen deposition, hydroxyproline content and αSMA expression as well as induced PparG expression reflected a significant reduction of fibrogenesis without adverse effects on healthy livers. Expression analyses of fibrotic and inflammatory genes revealed AON-specific regulatory effects on Ccl3, Ccl4, Ccl5, Mki67 and Notch3 expression. Further, AON treatment of MDR2-KO mice increased tissue infiltration by F4/80-positive cells including eosinophils, whereas the number of CD45-positive inflammatory cells decreased. In line, TGFB2 and CD45 expression correlated positively in PSC/PBC patients and localised in similar areas of the diseased liver tissue.
Conclusions: Taken together, our data suggest a new mechanistic explanation for amelioration of fibrogenesis by TGF-β2 silencing and provide a direct rationale for TGF-β2-directed drug development.
Background: Extremity fracture is frequently seen in multiple traumatized patients. Local post-traumatic inflammatory reactions as well as local and systemic interactions have been described in previous studies. However, trauma severity and its impact on the local immunologic reaction remains unclear. Therefore, fracture-associated local inflammation was investigated in a porcine model of isolated and combined trauma to gain information about the early inflammatory stages.
Material and Methods: Polytrauma (PT) consisted of lung contusion, liver laceration, femur fracture, and controlled hemorrhage. Monotrauma (MT) consisted of femur fracture only. The fracture was operatively stabilized and animals were monitored under ICU-standard for 72 h. Blood, fracture hematoma (FH) as well as muscle samples were collected throughout the experimental period. Levels of local and systemic pro- and anti-inflammatory as well as angiogenetic cytokines were measured by ELISA.
Results: Both groups showed a significant decrease in pro-inflammatory IL-6 in FH over time. However, concentrations in MT were significantly higher than in PT. The IL-8 concentrations initially decreased in FH, but recovered by the end of the observation period. These dynamics were only statistically significant in MT. Furthermore, concentrations measured in muscle tissue showed inverse kinetics compared to those in FH. The IL-10 did not present statistical resilient dynamics over time, although a slight increase in FH was seen by the end of the observation time in the MT group.
Conclusions: Time-dependent dynamics of the local inflammatory response were observed. Trauma severity showed a significant impact, with lower values in pro- as well as angiogenetic mediators. Fracture repair could be altered by these trauma-related changes of the local immunologic milieu, which might serve as a possible explanation for the higher rates of delayed or non-union bone repair in polytraumatised patients.
Cytomegalovirus (CMV) seropositivity in adults has been linked to increased cardiovascular disease burden. Phenotypically, CMV infection leads to an inflated CD8 T-lymphocyte compartment. We employed a 8-colour flow cytometric protocol to analyse circulating T cells in 597 octogenarians from the same birth cohort together with NT-proBNP measurements and followed all participants over 7 years. We found that, independent of CMV serostatus, a high number of CD27−CD28+ CD8 EMRA T-lymphocytes (TEMRA) protected from all-cause death after adjusting for known risk factors, such as heart failure, frailty or cancer (Hazard ratio 0.66 for highest vs lowest tertile; confidence interval 0.51–0.86). In addition, CD27−CD28+ CD8 EMRA T-lymphocytes protected from both, non-cardiovascular (hazard ratio 0.59) and cardiovascular death (hazard ratio 0.65). In aged mice treated with the senolytic navitoclax, in which we have previously shown a rejuvenated cardiac phenotype, CD8 effector memory cells are decreased, further indicating that alterations in T cell subpopulations are associated with cardiovascular ageing. Future studies are required to show whether targeting immunosenescence will lead to enhanced life- or healthspan.
Communication with the hematopoietic system is a vital component of regulating brain function in health and disease. Traditionally, the major routes considered for this neuroimmune communication are by individual molecules such as cytokines carried by blood, by neural transmission, or, in more severe pathologies, by the entry of peripheral immune cells into the brain. In addition, functional mRNA from peripheral blood can be directly transferred to neurons via extracellular vesicles (EVs), but the parameters that determine their uptake are unknown. Using varied animal models that stimulate neuronal activity by peripheral inflammation, optogenetics, and selective proteasome inhibition of dopaminergic (DA) neurons, we show that the transfer of EVs from blood is triggered by neuronal activity in vivo. Importantly, this transfer occurs not only in pathological stimulation but also by neuronal activation caused by the physiological stimulus of novel object placement. This discovery suggests a continuous role of EVs under pathological conditions as well as during routine cognitive tasks in the healthy brain.
Background: The health status, health awareness and health behavior of persons with a migration background often differ from the autochthonous population. Little is known about the proportion of patients with a migration background (PMB) that participate in primary care studies on oral antithrombotic treatment (OAT) in Germany, and whether the quality of their antithrombotic care differs from patients without a migration background. The aim of this paper was to use the results of a cluster-randomized controlled trial (PICANT) to determine the proportion of PMB at different stages of recruitment, and to compare the results in terms of sociodemographic characteristics and antithrombotic treatment.
Methods: This study used screening and baseline data from the PICANT trial on oral anticoagulation management in GP practices. For this analysis, we determined the proportion of PMB during the recruitment period at stage 1 (screening of potentially eligible patients), stage 2 (eligible patients invited to participate in the trial), and stage 3 (assessment of baseline characteristics of patients participating in the PICANT trial). In addition, we compared patients in terms of sociodemographic characteristics and quality of anticoagulant treatment. Statistical analysis comprised descriptive and bivariate analyses.
Results: The proportion of PMB at each recruitment stage declined from 9.1% at stage 1 to 7.9% at stage 2 and 7.3% at stage 3). A lack of German language skills led to the exclusion of half the otherwise eligible PMB. At stages 1 and 3, PMB were younger (stage 1: 70.7 vs. 75.0 years, p<0.001; stage 3: 70.2 vs. 73.5 years, p = 0.013), but did not differ in terms of gender. The quality of their anticoagulant care was comparable (100.0% vs. 99.1% were receiving appropriate OAT, 94.4% vs. 95.7% took phenprocoumon, or warfarin, and the most recent INR measurement of 60.8% vs. 69.3% was within their individual INR range).
Conclusions: In the potentially eligible population and among participants at baseline, the quality of anticoagulant care was high in all groups of patients, which is reassuring. To enable the inclusion of more PMB, future primary care research on OAT in Germany should address how best to overcome language barriers. This will be challenging, particularly because the heterogeneity of PMB means the resulting sample sizes for each specific language group are small.
Trial registration: Current Controlled Trials ISRCTN41847489.
In the context of data science, data projection and clustering are common procedures. The chosen analysis method is crucial to avoid faulty pattern recognition. It is therefore necessary to know the properties and especially the limitations of projection and clustering algorithms. This report describes a collection of datasets that are grouped together in the Fundamental Clustering and Projection Suite (FCPS). The FCPS contains 10 datasets with the names "Atom", "Chainlink", "EngyTime", "Golfball", "Hepta", "Lsun", "Target", "Tetra", "TwoDiamonds", and "WingNut". Common clustering methods occasionally identified non-existent clusters or assigned data points to the wrong clusters in the FCPS suite. Likewise, common data projection methods could only partially reproduce the data structure correctly on a two-dimensional plane. In conclusion, the FCPS dataset collection addresses general challenges for clustering and projection algorithms such as lack of linear separability, different or small inner class spacing, classes defined by data density rather than data spacing, no cluster structure at all, outliers, or classes that are in contact. This report describes a collection of datasets that are grouped together in the Fundamental Clustering and Projection Suite (FCPS). It is designed to address specific problems of structure discovery in high-dimensional spaces.
Background: Bone age (BA) assessment performed by artificial intelligence (AI) is of growing interest due to improved accuracy, precision and time efficiency in daily routine. The aim of this study was to investigate the accuracy and efficiency of a novel AI software version for automated BA assessment in comparison to the Greulich-Pyle method.
Methods: Radiographs of 514 patients were analysed in this retrospective study. Total BA was assessed independently by three blinded radiologists applying the GP method and by the AI software. Overall and gender-specific BA assessment results, as well as reading times of both approaches, were compared, while the reference BA was defined by two blinded experienced paediatric radiologists in consensus by application of the Greulich-Pyle method.
Results: Mean absolute deviation (MAD) and root mean square deviation (RSMD) were significantly lower between AI-derived BA and reference BA (MAD 0.34 years, RSMD 0.38 years) than between reader-calculated BA and reference BA (MAD 0.79 years, RSMD 0.89 years; p < 0.001). The correlation between AI-derived BA and reference BA (r = 0.99) was significantly higher than between reader-calculated BA and reference BA (r = 0.90; p < 0.001). No statistical difference was found in reader agreement and correlation analyses regarding gender (p = 0.241). Mean reading times were reduced by 87% using the AI system.
Conclusions: A novel AI software enabled highly accurate automated BA assessment. It may improve efficiency in clinical routine by reducing reading times without compromising the accuracy compared with the Greulich-Pyle method.
A systematic review on the burden of illness in individuals with tuberous sclerosis complex (TSC)
(2020)
Objective: This review will summarize current knowledge on the burden of illness (BOI) in tuberous sclerosis complex (TSC), a multisystem genetic disorder manifesting with hamartomas throughout the body, including mainly the kidneys, brain, skin, eyes, heart, and lungs.
Methods: We performed a systematic analysis of the available literature on BOI in TSC according to the PRISMA guidelines. All studies irrespective of participant age that reported on individual and societal measures of disease burden (e.g. health care resource use, costs, quality of life) were included.
Results: We identified 33 studies reporting BOI in TSC patients. Most studies (21) reported health care resource use, while 14 studies reported quality of life and 10 studies mentioned costs associated with TSC. Only eight research papers reported caregiver BOI. Substantial BOI occurs from most manifestations of the disorder, particularly from pharmacoresistant epilepsy, neuropsychiatric, renal and skin manifestations. While less frequent, pulmonary complications also lead to a high individual BOI. The range for the mean annual direct costs varied widely between 424 and 98,008 International Dollar purchasing power parities (PPP-$). Brain surgery, end-stage renal disease with dialysis, and pulmonary complications all incur particularly high costs. There is a dearth of information regarding indirect costs in TSC. Mortality overall is increased compared to general population; and most TSC related deaths occur as a result of complications from seizures as well as renal complications. Long term studies report mortality between 4.8 and 8.3% for a follow-up of 8 to 17.4 years.
Conclusions: TSC patients and their caregivers have a high burden of illness, and TSC patients incur high costs in health care systems. At the same time, the provision of inadequate treatment that does not adhere to published guidelines is common and centralized TSC care is received by no more than half of individuals who need it, especially adults. Further studies focusing on the cost effectiveness and BOI outcomes of coordinated TSC care as well as of new treatment options such as mTOR inhibitors are necessary.
Hepatitis Delta virus (HDV) is a satellite of Hepatitis B virus with a single-stranded circular RNA genome. HDV RNA genome synthesis is carried out in infected cells by cellular RNA polymerases with the assistance of the small hepatitis delta antigen (S-HDAg). Here we show that S-HDAg binds the bromodomain (BRD) adjacent to zinc finger domain 2B (BAZ2B) protein, a regulatory subunit of BAZ2B-associated remodeling factor (BRF) ISWI chromatin remodeling complexes. shRNA-mediated silencing of BAZ2B or its inactivation with the BAZ2B BRD inhibitor GSK2801 impairs HDV replication in HDV-infected human hepatocytes. S-HDAg contains a short linear interacting motif (SLiM) KacXXR, similar to the one recognized by BAZ2B BRD in histone H3. We found that the integrity of the S-HDAg SLiM sequence is required for S-HDAg interaction with BAZ2B BRD and for HDV RNA replication. Our results suggest that S-HDAg uses a histone mimicry strategy to co-activate the RNA polymerase II-dependent synthesis of HDV RNA and sustain HDV replication.
Creatinine and proteinuria are used to monitor kidney transplant patients. However, renal biopsies are needed to diagnose renal graft rejection. Here, we assessed whether the quantification of different urinary cells would allow non-invasive detection of rejection. Urinary cell numbers of CD4+ and CD8+ T cells, monocytes/macrophages, tubular epithelial cells (TEC), and podocalyxin(PDX)-positive cells were determined using flow cytometry and were compared to biopsy results. Urine samples of 63 renal transplant patients were analyzed. Patients with transplant rejection had higher amounts of urinary T cells than controls; however, patients who showed worsening graft function without rejection had similar numbers of T cells. T cells correlated with histological findings (interstitial inflammation p = 0.0005, r = 0.70; tubulitis p = 0.006, r = 0.58). Combining the amount of urinary T cells and TEC, or T cells and PDX+ cells, yielded a significant segregation of patients with rejection from patients without rejection (all p < 0.01, area under the curve 0.89–0.91). Urinary cell populations analyzed by flow cytometry have the potential to introduce new monitoring methods for kidney transplant patients. The combination of urinary T cells, TEC, and PDX-positive cells may allow non-invasive detection of transplant rejection.
Effective connectivity (EC) is able to explore causal effects between brain areas and can depict mechanisms that underlie repair and adaptation in chronic brain diseases. Thus, the application of EC techniques in multiple sclerosis (MS) has the potential to determine directionality of neuronal interactions and may provide an imaging biomarker for disease progression. Here, serial longitudinal structural and resting-state fMRI was performed at 12-week intervals over one year in twelve MS patients. Twelve healthy subjects served as controls (HC). Two approaches for EC quantification were used: Causal Bayesian Network (CBN) and Time-resolved Partial Directed Coherence (TPDC). The EC strength was correlated with the Expanded Disability Status Scale (EDSS) and Fatigue Scale for Motor and Cognitive functions (FSMC). Our findings demonstrated a longitudinal increase in EC between specific brain regions, detected in both the CBN and TPDC analysis in MS patients. In particular, EC from the deep grey matter, frontal, prefrontal and temporal regions showed a continuous increase over the study period. No longitudinal changes in EC were attested in HC during the study. Furthermore, we observed an association between clinical performance and EC strength. In particular, the EC increase in fronto-cerebellar connections showed an inverse correlation with the EDSS and FSMC. Our data depict continuous functional reorganization between specific brain regions indicated by increasing EC over time in MS, which is not detectable in HC. In particular, fronto-cerebellar connections, which were closely related to clinical performance, may provide a marker of brain plasticity and functional reserve in MS.
Speech perception is mediated by both left and right auditory cortices but with differential sensitivity to specific acoustic information contained in the speech signal. A detailed description of this functional asymmetry is missing, and the underlying models are widely debated. We analyzed cortical responses from 96 epilepsy patients with electrode implantation in left or right primary, secondary, and/or association auditory cortex (AAC). We presented short acoustic transients to noninvasively estimate the dynamical properties of multiple functional regions along the auditory cortical hierarchy. We show remarkably similar bimodal spectral response profiles in left and right primary and secondary regions, with evoked activity composed of dynamics in the theta (around 4–8 Hz) and beta–gamma (around 15–40 Hz) ranges. Beyond these first cortical levels of auditory processing, a hemispheric asymmetry emerged, with delta and beta band (3/15 Hz) responsivity prevailing in the right hemisphere and theta and gamma band (6/40 Hz) activity prevailing in the left. This asymmetry is also present during syllables presentation, but the evoked responses in AAC are more heterogeneous, with the co-occurrence of alpha (around 10 Hz) and gamma (>25 Hz) activity bilaterally. These intracranial data provide a more fine-grained and nuanced characterization of cortical auditory processing in the 2 hemispheres, shedding light on the neural dynamics that potentially shape auditory and speech processing at different levels of the cortical hierarchy.
Background: WATSU (portmanteau word: water and shiatsu) is a form of passive hydrotherapy in chest-deep thermoneutral water (35°C = 95°F = 308.15 K). It combines elements of myofascial stretching, joint mobilization, massage, and shiatsu and is reported to be used to address physical and mental issues. The objective of this systematic review (PROSPERO Registration No. CRD42016029347) and the meta-analyses was to assess the applications, indications, and the effects of WATSU to form a basis for further studies.
Methods: A search for "WATSU OR watershiatsu OR (water AND shiatsu)" was conducted without any restrictions in 32 databases. Peer reviewed original articles addressing WATSU as a stand-alone hydrotherapy were assessed for risk of bias. Quantitative data of effects on pain, physical function, and mental issues were processed in random model meta-analyses with subgroup analyses by study design. Effect sizes were expressed as Hedges's g (± 95% confidence intervals).
Results: Of 1,906 unique citations, 27 articles regardless of study design were assessed for risk of bias. WATSU has been applied to individuals of all ages. Indications covered acute (e.g. pregnancy related low back pain) and chronic conditions (e.g. cerebral palsy) with beneficial effects of WATSU regarding e.g. relaxation or sleep quality. Meta-analyses suggest beneficial effect sizes of WATSU on pain (overall Hedges’s g = -0.71, 95% CI = -0.91 to -0.51), physical function (overall Hedges’s g = -0.76, 95% CI = -1.08 to -0.44), and mental issues (overall Hedges’s g = -0.68, 95% CI = -1.02 to -0.35).
Conclusion: Various applications, indications and beneficial effects of WATSU were identified. The grade of this evidence is estimated to be low to moderate at the best. To strengthen the findings of this study, high-quality RCTs are needed.
Six dentin adhesives were tested in vitro regarding their cytotoxicity on human fibroblasts. The adhesives Hybrid Bond, One-up Bond F Plus, AdheSE, Clearfil SE Bond, Optibond Solo Plus and Syntac were eluted with culture medium as single or sequentially applied adhesive part for 24 h. 75 Petri dishes were produced per group. They were evaluated triangulated, comprising the quantitative evaluation (105 ones) to determine “viable”, “dead” and “debris” cells with the use of a cell-counter and the reactivity index was also identified based on the qualitative assessment (420 ones). One-up Bond F Plus, AdheSE and Clearfil SE Bond showed a statistical difference of viable cells to the cell control. For One-up Bond F Plus, statistically, differences compared to hybrid bond and Syntac were also found. All the adhesives except One-up Bond F Plus showed significant differences between single and sequentially applied adhesive part regarding the quantitative evaluation. The test material showed a moderate grade of cytotoxicity. As a result, a statistically significant difference of the cytotoxicity between the self-etch and etch-and-rinse adhesives cannot be demonstrated regarding the qualitative evaluation and the reactivity index, but the differences between sequentially applied and single applied components can be proved.
Complete reosseointegration after treatment of periimplantitis was never published yet. This short scientific communication reports about results of a randomized controlled preclinical study. An electrolytic approach was compared to a classical modality (ablative, cotton pellets soaked with sodium chloride solution and H2O2. For electrolytic cleaning a complete reosseointegration was achieved in several cases serving as a proof of concept.
Objective: Pancreatic ductal adenocarcinoma (PDAC) still carries a dismal prognosis with an overall 5-year survival rate of 9%. Conventional combination chemotherapies are a clear advance in the treatment of PDAC; however, subtypes of the disease exist, which exhibit extensive resistance to such therapies. Genomic MYC amplifications represent a distinct subset of PDAC with an aggressive tumour biology. It is clear that hyperactivation of MYC generates dependencies that can be exploited therapeutically. The aim of the study was to find and to target MYC-associated dependencies.
Design: We analysed human PDAC gene expression datasets. Results were corroborated by the analysis of the small ubiquitin-like modifier (SUMO) pathway in a large PDAC cohort using immunohistochemistry. A SUMO inhibitor was used and characterised using human and murine two-dimensional, organoid and in vivo models of PDAC.
Results: We observed that MYC is connected to the SUMOylation machinery in PDAC. Components of the SUMO pathway characterise a PDAC subtype with a dismal prognosis and we provide evidence that hyperactivation of MYC is connected to an increased sensitivity to pharmacological SUMO inhibition.
Conclusion: SUMO inhibitor-based therapies should be further developed for an aggressive PDAC subtype.
Introduction: There is still an ongoing debate whether a transrectal ultrasound (TRUS) approach for prostate biopsies is associated with higher (infectious) complications rates compared to transperineal biopsies. This is especially of great interests in settings with elevated frequencies of multidrug resistant organisms (MDRO).
Materials and Methods: Between 01/2018 and 05/2019 230 patients underwent a TRUS-guided prostate biopsy at the department of Urology at University Hospital Frankfurt. Patients were followed up within the clinical routine that was not conducted earlier than 6 weeks after the biopsy. Among 230 biopsies, 180 patients took part in the follow-up. No patients were excluded. Patients were analyzed retrospectively regarding complications, infections and underlying infectious agents or needed interventions.
Results: Of all patients with follow up, 84 patients underwent a systematic biopsy (SB) and 96 a targeted biopsy (TB) after MRI of the prostate with additional SB. 74.8% of the patients were biopsy-naïve. The most frequent objective complications (classified by Clavien-Dindo) lasting longer than one day after biopsy were hematuria (17.9%, n = 32), hematospermia (13.9%, n = 25), rectal bleeding (2.8%, n = 5), and pain (2.2%, n = 4). Besides a known high MDRO prevalence in the Rhine-Main region, only one patient (0.6%) developed fever after biopsy. One patient each (0.6%) consulted a physician due to urinary retention, rectal bleeding or gross hematuria. There were no significant differences in complications seen between SB and SB + TB patients. The rate of patients who consulted a physician was significantly higher for patients with one or more prior biopsies compared to biopsy-naïve patients.
Conclusion: Complications after transrectal prostate biopsies are rare and often self-limiting. Infections were seen in <1% of all patients, regardless of an elevated local prevalence of MDROs. Severe complications (Clavien-Dindo ≥ IIIa) were only seen in 3 (1.7%) of the patients. Repeated biopsy is associated with higher complication rates in general.
CD8+ T cells are key players in immunity against intracellular infections and tumors. The main cytokine associated with these protective responses is interferon-γ (IFN-γ), whose production is known to be regulated at the transcriptional level during CD8+ T cell differentiation. Here we found that microRNAs constitute a posttranscriptional brake to IFN-γ expression by CD8+ T cells, since the genetic interference with the Dicer processing machinery resulted in the overproduction of IFN-γ by both thymic and peripheral CD8+ T cells. Using a gene reporter mouse for IFN-γ locus activity, we compared the microRNA repertoires associated with the presence or absence of IFN-γ expression. This allowed us to identify a set of candidates, including miR-181a and miR-451, which were functionally tested in overexpression experiments using synthetic mimics in peripheral CD8+ T cell cultures. We found that miR-181a limits IFN-γ production by suppressing the expression of the transcription factor Id2, which in turn promotes the Ifng expression program. Importantly, upon MuHV-4 challenge, miR-181a-deficient mice showed a more vigorous IFN-γ+ CD8+ T cell response and were able to control viral infection significantly more efficiently than control mice. These data collectively establish a novel role for miR-181a in regulating IFN-γ–mediated effector CD8+ T cell responses in vitro and in vivo.
Biologics have transformed the treatment of immune-mediated inflammatory diseases such as rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). Biosimilars—biologic medicines with no clinically meaningful differences in safety or efficacy from licensed originators—can stimulate market competition and have the potential to expand patient access to biologics within the parameters of treatment recommendations. However, maximizing the benefits of biosimilars requires cooperation between multiple stakeholders. Regulators and developers should collaborate to ensure biosimilars reach patients rapidly without compromising stringent quality, safety, or efficacy standards. Pharmacoeconomic evaluations and payer policies should be updated following biosimilar market entry, minimizing the risk of imposing nonmedical barriers to biologic treatment. In RA, disparities between treatment guidelines and national reimbursement criteria could be addressed to ensure more uniform patient access to biologics and enable rheumatologists to effectively implement treat-to-target strategies. In IBD, the cost-effectiveness of biologic treatment earlier in the disease course is likely to improve when biosimilars are incorporated into pharmacoeconomic analyses. Patient understanding of biosimilars is crucial for treatment success and avoiding nocebo effects. Full understanding of biosimilars by physicians and carefully considered communication strategies can help support patients initiating or switching to biosimilars. Developers must operate efficiently to be sustainable, without undermining product quality, the reliability of the supply chain, or pharmacovigilance. Developers should also facilitate information sharing to meet the needs of other stakeholders. Such collaboration will help to ensure a sustainable future for both the biosimilar market and healthcare systems, supporting the availability of effective treatments for patients.
Broadly neutralizing antibodies (bNAbs) represent a promising approach to prevent and treat HIV-1 infection. However, viral escape through mutation of the HIV-1 envelope glycoprotein (Env) limits clinical applications. Here we describe 1-18, a new VH1-46-encoded CD4 binding site (CD4bs) bNAb with outstanding breadth (97%) and potency (GeoMean IC50 = 0.048 μg/mL). Notably, 1-18 is not susceptible to typical CD4bs escape mutations and effectively overcomes HIV-1 resistance to other CD4bs bNAbs. Moreover, mutational antigenic profiling uncovered restricted pathways of HIV-1 escape. Of most promise for therapeutic use, even 1-18 alone fully suppressed viremia in HIV-1-infected humanized mice without selecting for resistant viral variants. A 2.5-Å cryo-EM structure of a 1-18-BG505SOSIP.664 Env complex revealed that these characteristics are likely facilitated by a heavy-chain insertion and increased inter-protomer contacts. The ability of 1-18 to effectively restrict HIV-1 escape pathways provides a new option to successfully prevent and treat HIV-1 infection.
Background: Lipodystrophy syndromes comprise a group of extremely rare and heterogeneous diseases characterized by a selective loss of adipose tissue in the absence of nutritional deprivation or catabolic state. Because of the rarity of each lipodystrophy subform, research in this area is difficult and international co-operation mandatory. Therefore, in 2016, the European Consortium of Lipodystrophies (ECLip) decided to create a registry for patients with lipodystrophy.
Results: The registry was build using the information technology Open Source Registry System for Rare Diseases in the EU (OSSE), an open-source software and toolbox. Lipodystrophy specific data forms were developed based on current knowledge of typical signs and symptoms of lipodystrophy. The platform complies with the new General Data Protection Regulation (EU) 2016/679 by ensuring patient pseudonymization, informational separation of powers, secure data storage and security of communication, user authentication, person specific access to data, and recording of access granted to any data. Inclusion criteria are all patients with any form of lipodystrophy (with the exception of HIV-associated lipodystrophy). So far 246 patients from nine centres (Amsterdam, Bologna, Izmir, Leipzig, Münster, Moscow, Pisa, Santiago de Compostela, Ulm) have been recruited. With the help from the six centres on the brink of recruitment (Cambridge, Lille, Nicosia, Paris, Porto, Rome) this number is expected to double within the next one or 2 years.
Conclusions: A European registry for all patients with lipodystrophy will provide a platform for improved research in the area of lipodystrophy. All physicians from Europe and neighbouring countries caring for patients with lipodystrophy are invited to participate in the ECLip Registry.
Study registration: ClinicalTrials.gov (NCT03553420). Registered 14 March 2018, retrospectively registered.
Cholinesterase alterations in delirium after cardiosurgery: a German monocentric prospective study
(2020)
Objectives: Postoperative delirium (POD) is a common complication after elective cardiac surgery. Recent evidence indicates that a disruption in the normal activity of the cholinergic system may be associated with delirium.
Design: Prospective observational study.
Setting: Single-centre at a European academic hospital.
Primary: and secondary outcome measures In our study the enzyme activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were determined preoperatively as well as on the first and second postoperative day. The confusion assessment method for the intensive care unit was used to screen patients for the presence of POD.
Results: A total of 114 patients were included in the study. POD was associated with a decrease in BChE activity on postoperative day 1 (p=0.03). In addition, patients who developed POD, had significantly lower preoperative AChE activity than patients without POD (p<0.01). Multivariate analysis identified a preoperatively decreased AChE activity (OR 3.1; 95% CI 1.14 to 8.46), anticholinergic treatment (OR 5.09; 95% CI 1.51 to 17.23), elevated European System for Cardiac Operative Risk Evaluation (OR 3.68; 95% CI 1.04 to 12.99) and age (OR 3.02; 95% CI 1.06 to 8.62) to be independently associated with the development of POD.
Conclusions: We conclude that a reduction in the acetylcholine hydrolysing enzyme activity in patients undergoing cardiac surgery may correlate with the development of POD.
Ubiquitination regulates nearly all cellular processes by coordinated activity of ubiquitin writers (E1, E2, and E3 enzymes), erasers (deubiquitinating enzymes) and readers (proteins that recognize ubiquitinated proteins by their ubiquitin-binding domains). By differentially modifying cellular proteome and by recognizing these ubiquitin modifications, ubiquitination machinery tightly regulates execution of specific cellular events in space and time. Dynamic and complex ubiquitin architecture, ranging from monoubiquitination, multiple monoubiquitination, eight different modes of homotypic and numerous types of heterogeneous polyubiquitin linkages, enables highly dynamic and complex regulation of cellular processes. We discuss available tools and approaches to study ubiquitin networks, including methods for the identification and quantification of ubiquitin-modified substrates, as well as approaches to quantify the length, abundance, linkage type and architecture of different ubiquitin chains. Furthermore, we also summarize the available approaches for the discovery of novel ubiquitin readers and ubiquitin-binding domains, as well as approaches to monitor and visualize activity of ubiquitin conjugation and deconjugation machineries. We also discuss benefits, drawbacks and limitations of available techniques, as well as what is still needed for detailed spatiotemporal dissection of cellular ubiquitination networks
Motor function after hemispheric lesions has been associated with the structural integrity of either the pyramidal tract (PT) or alternate motor fibers (aMF). In this study, we aimed to differentially characterize the roles of PT and aMF in motor compensation by relating diffusion-tensor-imaging-derived parameters of white matter microstructure to measures of proximal and distal motor function in patients after hemispherotomy. Twenty-five patients (13 women; mean age: 21.1 years) after hemispherotomy (at mean age: 12.4 years) underwent Diffusion Tensor Imaging and evaluation of motor function using the Fugl-Meyer Assessment and the index finger tapping test. Regression analyses revealed that fractional anisotropy of the PT explained (p = 0.050) distal motor function including finger tapping rate (p = 0.027), whereas fractional anisotropy of aMF originating in the contralesional cortex and crossing to the ipsilesional hemisphere in the pons explained proximal motor function (p = 0.001). Age at surgery was found to be the only clinical variable to explain motor function (p < 0.001). Our results are indicative of complementary roles of the PT and of aMF in motor compensation of hemispherotomy mediating distal and proximal motor compensation of the upper limb, respectively.
STF-62247 and pimozide induce autophagy and autophagic cell death in mouse embryonic fibroblasts
(2020)
Induction of autophagy can have beneficial effects in several human diseases, e.g. cancer and neurodegenerative diseases (ND). Here, we therefore evaluated the potential of two novel autophagy-inducing compounds, i.e. STF-62247 and pimozide, to stimulate autophagy as well as autophagic cell death (ACD) using mouse embryonic fibroblasts (MEFs) as a cellular model. Importantly, both STF-62247 and pimozide triggered several hallmarks of autophagy in MEFs, i.e. enhanced levels of LC3B-II protein, its accumulation at distinct cytosolic sites and increase of the autophagic flux. Intriguingly, autophagy induction by STF-62247 and pimozide resulted in cell death that was significantly reduced in ATG5- or ATG7-deficient MEFs. Consistent with ACD induction, pharmacological inhibitors of apoptosis, necroptosis or ferroptosis failed to protect MEFs from STF-62247- or pimozide-triggered cell death. Interestingly, at subtoxic concentrations, pimozide stimulated fragmentation of the mitochondrial network, degradation of mitochondrial proteins (i.e. mitofusin-2 and cytochrome c oxidase IV (COXIV)) as well as a decrease of the mitochondrial mass, indicative of autophagic degradation of mitochondria by pimozide. In conclusion, this study provides novel insights into the induction of selective autophagy as well as ACD by STF-62247 and pimozide in MEFs.