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: Re-treatment in patients with a chronic hepatitis C virus (HCV) infection and a previous failure to direct-acting antiviral (DAA) treatment remains a challenge. Therefore, we investigated the success rate of treatment and re-treatment regimens used at our center from October 2011 to March 2018.
Methods: A retrospective analysis of DAA-based HCV therapies of 1096 patients was conducted. Factors associated with a virological relapse were identified by univariable and multivariable logistic regression, treatment success of the re-treatment regimens was evaluated by an analysis of sustained virological response (SVR) rates in patients with a documented follow-up 12 weeks after the end of treatment.
Results: Of 1096 patients treated with DAA-based regimens, 91 patients (8%) were lost to follow-up, 892 of the remaining 1005 patients (89%) achieved an SVR12. Most patients (65/113, 58%) who experienced a virological relapse received an interferon-based DAA regimen. SVR rates were comparable in special cohorts like liver transplant recipients (53/61, 87%) and people with a human immunodeficiency virus (HIV) coinfection (41/45, 91%). On multivariable analysis, interferon-based DAA therapy was associated with treatment failure (odds ratio 0.111, 95%-confidence interval 0.054–0.218) among others. One hundred seventeen patients with multiple DAA treatment courses were identified, of which 97 patients (83%) experienced a single relapse, but further relapses after two (18/117, 15%) or even three (2/117, 2%) treatment courses were also observed. Eighty-two of 96 (85%) re-treatment attempts with all-oral DAA regimens were successful after an initial treatment failure.
Conclusion: Overall, DAA re-treatments were highly effective in this real-world cohort and only a minority of patients failed more than two treatment courses. Switching to–or addition of–a new drug class seem to be valid options for the re-treatment of patients especially after failure of an interferon-based regimen.
A myriad of signaling molecules in a heuristic network of the tumor microenvironment (TME) pose a challenge and an opportunity for novel therapeutic target identification in human cancers. MicroRNAs (miRs), due to their ability to affect signaling pathways at various levels, take a prominent space in the quest of novel cancer therapeutics. The role of miRs in cancer initiation, progression, as well as in chemoresistance, is being increasingly investigated. The canonical function of miRs is to target mRNAs for post-transcriptional gene silencing, which has a great implication in first-order regulation of signaling pathways. However, several reports suggest that miRs also perform non-canonical functions, partly due to their characteristic non-coding small RNA nature. Examples emerge when they act as ligands for toll-like receptors or perform second-order functions, e.g., to regulate protein translation and interactions. This review is a compendium of recent advancements in understanding the role of miRs in cancer signaling and focuses on the role of miRs as novel regulators of the signaling pathway in the TME.
The survivin suppressant YM155 is a drug candidate for neuroblastoma. Here, we tested YM155 in 101 neuroblastoma cell lines (19 parental cell lines, 82 drug-adapted sublines). Seventy seven (77) cell lines displayed YM155 IC50s in the range of clinical YM155 concentrations. ABCB1 was an important determinant of YM155 resistance. The activity of the ABCB1 inhibitor zosuquidar ranged from being similar to that of the structurally different ABCB1 inhibitor verapamil to being 65-fold higher. ABCB1 sequence variations may be responsible for this, suggesting that the design of variant-specific ABCB1 inhibitors may be possible. Further, we showed that ABCC1 confers YM155 resistance. Previously, p53 depletion had resulted in decreased YM155 sensitivity. However, TP53-mutant cells were not generally less sensitive to YM155 than TP53 wild-type cells in this study. Finally, YM155 cross-resistance profiles differed between cells adapted to drugs as similar as cisplatin and carboplatin. In conclusion, the large cell line panel was necessary to reveal an unanticipated complexity of the YM155 response in neuroblastoma cell lines with acquired drug resistance. Novel findings include that ABCC1 mediates YM155 resistance and that YM155 cross-resistance profiles differ between cell lines adapted to drugs as similar as cisplatin and carboplatin.
Objective: Severely injured patients frequently develop an immunological imbalance following the traumatic insult, which might result in infectious complications evoked by a persisting immunosuppression. Regulatory T cells (Tregs) maintain the immune homeostasis by suppressing proinflammatory responses, however, their functionality after trauma is unclear. Here, we characterized the role of Tregs in regulating the proliferation of CD4+ lymphocytes in traumatized patients (TP). Methods: Peripheral blood was obtained daily from 29 severely injured TP (Injury Severity Score, ISS ≥16) for ten days following admission to the emergency department (ED). Ten healthy volunteers (HV) served as controls. The frequency and activity of Tregs were assessed by flow cytometry. Proliferation of CD4+ cells was analyzed either in presence or absence of Tregs, or after blocking of either IL-10 or IL-10R1. Results: The frequencies of CD4+CD25high and CD4+CD25+CD127− Tregs were significantly decreased immediately upon admission of TP to the ED and during the following 10 post-injury days. Compared with HV CD4+ T cell proliferation in TP increased significantly upon their admission and on the following days. As expected, CD4+CD25+CD127− Tregs reduced the proliferation of CD4+ cells in HV, nevertheless, CD4+ proliferation in TP was increased by Tregs. Neutralization of IL-10 as well as blocking the IL-10R1 increased further CD4+ T cell proliferation in Tregs-depleted cultures, thereby confirming an IL-10-mediated mechanism of IL-10-regulated CD4+ T cell proliferation. Neutralization of IL-10 in TP decreased CD4+ T cell proliferation in Tregs-depleted cultures, whereas blocking of the IL-10R1 receptor had no significant effects. Conclusions: The frequency of Tregs in the CD4+ T lymphocyte population is reduced after trauma; however, their inductiveness is increased. The mechanisms of deregulated influence of Tregs on CD4+ T cell proliferation are mediated via IL-10 but not via the IL-10R1.
Survivin is a drug target and its suppressant YM155 a drug candidate mainly investigated for high-risk neuroblastoma. Findings from one YM155-adapted subline of the neuroblastoma cell line UKF-NB-3 had suggested that increased ABCB1 (mediates YM155 efflux) levels, decreased SLC35F2 (mediates YM155 uptake) levels, decreased survivin levels, and TP53 mutations indicate YM155 resistance. Here, the investigation of 10 additional YM155-adapted UKF-NB-3 sublines only confirmed the roles of ABCB1 and SLC35F2. However, cellular ABCB1 and SLC35F2 levels did not indicate YM155 sensitivity in YM155-naïve cells, as indicated by drug response data derived from the Cancer Therapeutics Response Portal (CTRP) and the Genomics of Drug Sensitivity in Cancer (GDSC) databases. Moreover, the resistant sublines were characterized by a remarkable heterogeneity. Only seven sublines developed on-target resistance as indicated by resistance to RNAi-mediated survivin depletion. The sublines also varied in their response to other anti-cancer drugs. In conclusion, cancer cell populations of limited intrinsic heterogeneity can develop various resistance phenotypes in response to treatment. Therefore, individualized therapies will require monitoring of cancer cell evolution in response to treatment. Moreover, biomarkers can indicate resistance formation in the acquired resistance setting, even when they are not predictive in the intrinsic resistance setting.
Although the big tobacco companies offer the same cigarette brands across countries, little is known about the potential regional differences of the particulate matter (PM) emissions of apparently equal brands. PM emissions of three cigarette brands (Marlboro Gold, Winston Red resp. Classic, Parliament Platinum resp. Night Blue) from the United Arab Emirates (UAE) and Germany were analysed. Second-hand smoke was produced in a 2.88 m3 measuring cabin by an automatic environmental tobacco smoke emitter. PM size fractions PM10, PM2.5, and PM1 were detected in real-time using laser aerosol spectrometry. Depending on the PM fraction Marlboro cigarettes from UAE showed 33%–35% higher PM amounts. Moreover, Winston cigarettes from UAE showed distinctly higher PM values (28–31%) than the German counterparts. The “lighter” Parliament from UAE emitted 3%–9% more PM than the German one. The measured mean PM10 values laid between 778 and 1163 µg/m3 (mean PM2.5: 777–1161 µg/m3; mean PM1: 724–1074 µg/m3). That means smoking in enclosed rooms causes massive PM burden. The PM emission of equal or similar tobacco products from different countries can differ distinctly. Hence, the declaration of PM emission values, besides nicotine, tar, and carbon monoxide amounts, should be obligatory worldwide. Furthermore, complete information about the ingredients and production processes of tobacco products should be provided to health officials and the public. This can help to minimise or ban substances or product designs that make smoking even more harmful, and to enhance the awareness of the risks of smoking.
Obtaining sufficient numbers of functional natural killer (NK) cells is crucial for the success of NK-cell-based adoptive immunotherapies. While expansion from peripheral blood (PB) is the current method of choice, ex vivo generation of NK cells from hematopoietic stem and progenitor cells (HSCs) may constitute an attractive alternative. Thereby, HSCs mobilized into peripheral blood (PB-CD34+) represent a valuable starting material, but the rather poor and donor-dependent differentiation of isolated PB-CD34+ cells into NK cells observed in earlier studies still represents a major hurdle. Here, we report a refined approach based on ex vivo culture of PB-CD34+ cells with optimized cytokine cocktails that reliably generates functionally mature NK cells, as assessed by analyzing NK-cell-associated surface markers and cytotoxicity. To further enhance NK cell expansion, we generated K562 feeder cells co-expressing 4-1BB ligand and membrane-anchored IL-15 and IL-21. Co-culture of PB-derived NK cells and NK cells that were ex-vivo-differentiated from HSCs with these feeder cells dramatically improved NK cell expansion, and fully compensated for donor-to-donor variability observed during only cytokine-based propagation. Our findings suggest mobilized PB-CD34+ cells expanded and differentiated according to this two-step protocol as a promising source for the generation of allogeneic NK cells for adoptive cancer immunotherapy.
Background: This study investigated whether work ability is associated with the duration of unemployment, heart rate variability (HRV), and the level of physical activity. Methods: Thirty-four unemployed persons (mean 55.7 ± standard deviation 33.3 years, 22 female, 12 male, unemployed: range 1–22.5 years) participated in the cross-sectional study. The Work Ability Index (WAI) and International Physical Activity Questionnaire (IPAQ) were applied. Short-term (five minutes) resting HRV (Low Frequency (LF), High Frequency (HF), Total Power (TP)) was collected. Results: Work ability was positively associated with the HRV: LF (r = 0.383; p = 0.025), HF (r = 0.412; p = 0.015) and TP (r = 0.361; p = 0.036). The WAI showed a positive linear correlation with the amount of total physical activity (r = 0.461; p = 0.006) as well as with the amount of moderate to vigorous physical activity (r = 0.413; p = 0.015). No association between the WAI and the duration of unemployment occurred. Conclusions: the relation between self-perceived work ability, health-associated parameters, the HRV and the level of physical activity points out the relevance of health-care exercise and the need of stress-reducing interventions to improve perceived work ability. Our results point out the need for the further and more holistic development of healthcare for the unemployed.
According to the free radical theory of aging, reactive oxygen species (ROS) have been proposed to be a major cause of aging for a long time. Meanwhile, it became clear that ROS have diverse functions in a healthy organism. They act as second messengers, and as transient inhibitors of phosphatases and others. In fact, their detrimental role is highly dependent on the context of their production. NADPH oxidases (Nox) have been discovered as a controllable source of ROS. NoxO1 enables constitutive ROS formation by Nox1 by acting as a constitutively active cytosolic subunit of the complex. We previously found that both Nox1 and NoxO1 were highly expressed in the colon, and that NoxO1-/- deficiency reduces colon health. We hypothesized that a healthy colon potentially contributes to longevity and NoxO1 deficiency would reduce lifetime, at least in mouse. In contrast, here we provide evidence that the knockout of NoxO1 results in an elongated life expectancy of mice. No better endothelial function, nor an improved expression of genes related to longevity, such as Sirt1, were found, and therefore may not serve as an explanation for a longer life in NoxO1 deficiency. Rather minor systemic differences, such as lower body weight occur. As a potential reason for longer life, we suggest better DNA repair capacity in NoxO1 deficient mice. Although final fatal DNA damage appears similar between wildtype and NoxO1 knockout animals, we identified less intermediate DNA damage in colon cells of NoxO1-/- mice, while the number of cells with intact DNA is elevated in NoxO1-/- colons. We conclude that NoxO1 deficiency prolongs lifetime of mice, which correlates with less intermediate and potentially fixable DNA damage at least in colon cells.
Objective: To evaluate prognostic factors in pediatric patients with gonadal germ cell tumors (GCT). Methods: Patients <18 years with ovarian and testicular GCT (respectively OGCT and TGCT) were prospectively registered according to the guidelines of MAKEI 96. After resection of the primary tumor, patients staged ≥II received risk-stratified cisplatin-based combination chemotherapy. Patients were analyzed in respect to age (six age groups divided into 3-year intervals), histology, stage, and therapy. The primary end point was overall survival. Results: Between January 1996 and March 2016, the following patients were registered: 1047 OGCT, of those, 630 had ovarian teratoma (OTER) and 417 had malignant OGCT (MOGCT); and 418 TGCT, of those, 106 had testicular teratoma (TTER) and 312 had malignant TGCT (MTGCT). Only in MTGCT, older age correlated with a higher proportion of advanced tumors. All 736 teratomas and 240/415 stage I malignant gonadal GCT underwent surgery and close observation alone. In case of watchful waiting, the progression rate of OGCT was higher than that of TGCT. However, death from disease was reported in 8/417 (1.9%) MOGCT and 8/312 (2.6%) MTGCT irrespective of adjuvant chemotherapy and repeated surgery. Conclusions: The different pathogenesis and histogenesis of gonadal GCT reflects sex- and age-specific patterns that define clinically relevant risk groups. Therefore, gender and age should be considered in further research on the biology and clinical practice of pediatric gonadal GCT.
Competition anxiety has been demonstrated to decrease sports performance while increasing burnout risk. To date, its degree in CrossFit (CF) is unknown. The present study, therefore, examines competition fear and relevant coping skills as well as potential correlates of both in individuals participating in CF events. A total of n = 79 athletes answered a battery of three questionnaires (competition fear index, athletic coping skills inventory, mindfulness attention awareness scale). Substantial levels of anxiety, particularly regarding the somatic dimension of the competition fear index, were reported. The most pronounced coping skill was freedom of worry. While age or level of competition showed no/very small associations with survey data, sex was correlated to the psychological characteristics: women reported higher competition fears and lower coping skill levels (p > 0.05). Competition fears are highly prevalent in CF athletes and the preventive value of population-specific interventions, particularly in females, should be investigated in future trials.
Background: Body dysmorphic disorder (BDD) is characterized by an excessive preoccupation with one or more perceived flaws in one’s own appearance. Previous studies provided evidence for deficits in configural and holistic processing in BDD. Preliminary evidence suggests abnormalities at an early stage of visual processing. The present study is the first examining early neurocognitive perception of the own face in BDD by using electroencephalography (EEG). We investigated the face inversion effect, in which inverted (upside-down) faces are disproportionately poorly processed compared to upright faces. This effect reflects a disruption of configural and holistic processing, and in consequence a preponderance of featural face processing.
Methods: We recorded face-sensitive event-related potentials (ERPs) in 16 BDD patients and 16 healthy controls, all unmedicated. Participants viewed upright and inverted (upside-down) images of their own face and an unfamiliar other face, each in two facial emotional expressions (neutral vs. smiling). We calculated the early ERP components P100, N170, P200, N250, and the late positive component (LPC), and compared amplitudes among both groups.
Results: In the early P100, no face inversion effects were found in both groups. In the N170, both groups exhibited the common face inversion effects, with significantly larger N170 amplitudes for inverted than upright faces. In the P200, both groups exhibited larger inversion effects to other (relative to own) faces, with larger P200 amplitudes for other upright than inverted faces. In the N250, no significant group differences were found in face processing. In the LPC, both groups exhibited larger inversion effects to other (relative to own) faces, with larger LPC amplitudes for other inverted than upright faces. These overall patterns appeared to be comparable for both groups. Smaller inversion effects to own (relative to other) faces were observed in none of these components in BDD, relative to controls.
Conclusions: The findings suggest no evidence for abnormalities at all levels of early face processing in our observed sample of BDD patients. Further research should investigate the neural substrates underlying BDD symptomatology.
This open access book presents a unique collection of practical examples from the field of pharma business management and research. It covers a wide range of topics such as: "Brexit and its Impact on pharmaceutical Law - Implications for Global Pharma Companies", "Implementation of Measures and Sustainable Actions to Improve Employee's Engagement", "Global Medical Clinical and Regulatory Affairs (GMCRA)", and "A Quality Management System for R&D Project and Portfolio Management in a Pharmaceutical Company".
The chapters are summaries of master’s theses by "high potential" Pharma MBA students from the Goethe Business School, Frankfurt/Main, Germany, with 8-10 years of work experience and are based on scientific know-how and real-world experience. The authors applied their interdisciplinary knowledge gained in 22 months of studies in the MBA program to selected practical themes drawn from their daily business.
Introduction: Bipolar disorder (BD) is characterized by recurrent episodes of depression and mania and affects up to 2% of the population worldwide. Patients suffering from bipolar disorder have a reduced life expectancy of up to 10 years. The increased mortality might be due to a higher rate of somatic diseases, especially cardiovascular diseases. There is however also evidence for an increased rate of diabetes mellitus in BD, but the reported prevalence rates vary by large.
Material and Methods: 85 bipolar disorder patients were recruited in the framework of the BiDi study (Prevalence and clinical features of patients with Bipolar Disorder at High Risk for Type 2 Diabetes (T2D), at prediabetic state and with manifest T2D) in Dresden and Würzburg. T2D and prediabetes were diagnosed measuring HBA1c and an oral glucose tolerance test (oGTT), which at present is the gold standard in diagnosing T2D. The BD sample was compared to an age-, sex- and BMI-matched control population (n = 850) from the Study of Health in Pomerania cohort (SHIP Trend Cohort).
Results: Patients suffering from BD had a T2D prevalence of 7%, which was not significantly different from the control group (6%). Fasting glucose and impaired glucose tolerance were, contrary to our hypothesis, more often pathological in controls than in BD patients. Nondiabetic and diabetic bipolar patients significantly differed in age, BMI, number of depressive episodes, and disease duration.
Discussion: When controlled for BMI, in our study there was no significantly increased rate of T2D in BD. We thus suggest that overweight and obesity might be mediating the association between BD and diabetes. Underlying causes could be shared risk genes, medication effects, and lifestyle factors associated with depressive episodes. As the latter two can be modified, attention should be paid to weight changes in BD by monitoring and taking adequate measures to prevent the alarming loss of life years in BD patients.
Introduction: Affective disorders are a major global burden, with approximately 15% of people worldwide suffering from some form of affective disorder. In patients experiencing their first depressive episode, in most cases it cannot be distinguished whether this is due to bipolar disorder (BD) or major depressive disorder (MDD). Valid fluid biomarkers able to discriminate between the two disorders in a clinical setting are not yet available.
Material and Methods: Seventy depressed patients suffering from BD (bipolar I and II subtypes) and 42 patients with major MDD were recruited and blood samples were taken for proteomic analyses after 8 h fasting. Proteomic profiles were analyzed using the Multiplex Immunoassay platform from Myriad Rules Based Medicine (Myriad RBM; Austin, Texas, USA). Human DiscoveryMAPTM was used to measure the concentration of various proteins, peptides, and small molecules. A multivariate predictive model was consequently constructed to differentiate between BD and MDD.
Results: Based on the various proteomic profiles, the algorithm could discriminate depressed BD patients from MDD patients with an accuracy of 67%.
Discussion: The results of this preliminary study suggest that future discrimination between bipolar and unipolar depression in a single case could be possible, using predictive biomarker models based on blood proteomic profiling.
Hintergrund: Das genaue Wissen um die Umstände eines jeden tödlichen Arbeitsunfalls ist Voraussetzung für die Identifizierung von Unfallschwerpunkten und ermöglicht eine effektive Präventionsarbeit. Mit dieser rechtsmedizinischen Studie zum Arbeitsunfallgeschehen soll ein Beitrag dazu geleistet werden, die Zahl tödlicher Arbeitsunfälle in Deutschland zu senken.
Material und Methode: Zur Untersuchung kamen die tödlichen Arbeitsunfälle, die sich im Einzugsbereich des rechtsmedizinischen Instituts Frankfurt am Main in den Jahren von 2005 bis 2016 ereigneten. Ausgewertet wurden Obduktionsprotokolle sowie die dem Institut zur Verfügung gestellten staatsanwaltschaftlichen Ermittlungsakten.
Ergebnisse: Es fanden sich 87 tödliche Arbeitsunfälle in dem genannten Zwölfjahreszeitraum. Die Altersstruktur reichte vom jugendlichen Alter bis in das Rentenalter. Betroffen waren zum größten Teil männliche Arbeiter (96,6 %, p < 0,0001), verhältnismäßig häufig ausländischer Nationalität (34,5 %). Die meisten Unfälle ereigneten sich in der 2. Jahreshälfte (58,6 %), an Montagen (26,4 %), kurz vor und nach der Mittagspause. In 3 Fällen lag die Blutalkoholkonzentration über 0,5‰. Die Baubranche (55,2 %) war der unfallträchtigste Wirtschaftszweig. Der Absturz (28,7 %) war der häufigste Unfallmechanismus und das Polytrauma (39,1 %) gemeinsam mit dem Schädel-Hirn-Trauma (24,1 %) gemäß dem ISS die häufigste Todesursache.
Diskussion: Nach den Ergebnissen dieser Studie sollten Alter der Arbeiter sowie die Tages‑, Wochen- und Jahreszeit bei der Ausführung risikoreicher Arbeiten im Baugewerbe berücksichtigt werden. Besonderes Augenmerk sollten Arbeitgeber auf die Kontrolle von Sicherheitsvorkehrungen bei Arbeiten in der Höhe sowie auf die Durchsetzung der Helmpflicht gerade auch bei ausländischen Arbeitnehmern legen.
Bronchiolitis obliterans (BO) is a rare, chronic form of obstructive lung disease, often initiated with injury of the bronchiolar epithelium followed by an inflammatory response and progressive fibrosis of small airways resulting in nonuniform luminal obliteration or narrowing. The term BO comprises a group of diseases with different underlying etiologies, courses, and characteristics. Among the better recognized inciting stimuli leading to BO are airway pathogens such as adenovirus and mycoplasma, which, in a small percentage of infected children, will result in progressive fixed airflow obstruction, an entity referred to as postinfectious bronchiolitis obliterans (PIBO). The present knowledge on BO in general is reasonably well developed, in part because of the relatively high incidence in patients who have undergone lung transplantation or bone marrow transplant recipients who have had graft-versus-host disease in the posttransplant period. The cellular and molecular pathways involved in PIBO, while assumed to be similar, have not been adequately elucidated. Since 2016, an international consortium of experts with an interest in PIBO assembles on a regular basis in Geisenheim, Germany, to discuss key areas in PIBO which include diagnostic workup, treatment strategies, and research fields.
Our study is the first to objectively assess sleep and sleep-related respiration in orchestra musicians. We hypothesized low sleep quality due to high work demands and irregular work-sleep schedules, and a better respiration for wind instrument (WI) players than string instrument (SI) players due to habitual upper airway muscles training. We recorded overnight polysomnography with 29 professional orchestra musicians (21 men, 14 WI/ 15 SI). The musicians presented a sleep efficiency of 88% (IQR 82–92%) with WI having a significant higher sleep efficiency than SI (89%, 85–93% vs. 85%, 74–89%; p = 0.029). The group had a total sleep time around 6 hours (377min, 340-421min) with signs of increased NREM 1 (light sleep) and decreased REM (dream sleep). The musicians displayed an apnea-hypopnea-index of 2.1events/hour (0.7–5.5) and an oxygen saturation of 98% (97–100%). While SI player exhibited declining sleep-related respiration with age (breathing events: r = 0.774, p = 0.001, oxygen: r = -0.647, p = 0.009), WI player showed improved respiration with age (breathing events: r = -0.548, p = 0.043; oxygen: r = 0.610, p = 0.020). Our study is the first objective investigation of sleep pattern and respiration during sleep with overnight polysomnography in professional orchestra musicians. While sleep and respiration were unexpectedly good, our results revealed possible signs of sleep deprivation and an interesting age-related pattern on respiration depending on instrument. While sample size was small and results modest, these findings present first objective evidence towards the assumption that habitual playing of a WI–and training of the upper airway muscles–may have a protective effect on respiration.
Serum levels of bone sialoprotein correlate with portal pressure in patients with liver cirrhosis
(2020)
Liver cirrhosis represents the common end-stage of chronic liver diseases regardless of its etiology. Patients with compensated disease are mostly asymptomatic, however, progression to a decompensated disease stage is common. The available stratification strategies are often unsuitable to identify patients with a higher risk for disease progression and a limited prognosis. SIBLINGs, soluble glycophosphoproteins, are secreted into the blood by immune-cells. While osteopontin, the most prominent member of the SIBLINGs family, has been repeatedly associated with liver cirrhosis, data on the diagnostic and/or prognostic value of bone sialoprotein (BSP) are scarce and partly inconclusive. In this study, we analyzed the diagnostic and prognostic potential of circulating BSP in comparison to other standard laboratory markers in a large cohort of patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt (TIPS). Serum levels of BSP were similar in patients with different disease stages and were not indicative for prognosis. Interestingly, BSP serum levels did correlate inversely with portal pressure, as well as its surrogates such as platelet count, the portal vein cross-sectional area and correlated positively with the portal venous velocity. In summary, our data highlight that BSP might represent a previously unrecognized marker for portal hypertension in patients with liver cirrhosis.
In resource-limited or point-of-care settings, rapid diagnostic tests (RDTs), that aim to simultaneously detect HIV antibodies and p24 capsid (p24CA) antigen with high sensitivity, can pose important alternatives to screen for early infections. We evaluated the performance of the antibody and antigen components of the old and novel version of the Determine™ HIV-1/2 Ag/Ab Combo RDTs in parallel to quantifications in a fourth-generation antigen/antibody immunoassay (4G-EIA), p24CA antigen immunoassay (p24CA-EIA), immunoblots, and nucleic acid quantification. We included plasma samples of acute, treatment-naïve HIV-1 infections (Fiebig stages I–VI, subtypes A1, B, C, F, CRF02_AG, CRF02_AE, URF) or chronic HIV-1 and HIV-2 infections. The tests’ antigen component was evaluated also for a panel of subtype B HIV-1 transmitted/founder (T/F) viruses, HIV-2 strains and HIV-2 primary isolates. Furthermore, we assessed the analytical sensitivity of the RDTs to detect p24CA using a highly purified HIV-1NL4-3 p24CA standard. We found that 77% of plasma samples from acutely infected, immunoblot-negative HIV-1 patients in Fiebig stages II–III were identified by the new RDT, while only 25% scored positive in the old RDT. Both RDTs reacted to all samples from chronically HIV-1-infected and acutely HIV-1-infected patients with positive immunoblots. All specimens from chronically infected HIV-2 patients scored positive in the new RDT. Of note, the sensitivity of the RDTs to detect recombinant p24CA from a subtype B virus ranged between 50 and 200 pg/mL, mirrored also by the detection of HIV-1 T/F viruses only at antigen concentrations tenfold higher than suggested by the manufacturer. The RTD failed to recognize any of the HIV-2 viruses tested. Our results indicate that the new version of the Determine™ HIV-1/2 Ag/Ab Combo displays an increased sensitivity to detect HIV-1 p24CA-positive, immunoblot-negative plasma samples compared to the precursor version. The sensitivity of 4G-EIA and p24CA-EIA to detect the major structural HIV antigen, and thus to diagnose acute infections prior to seroconversion, is still superior.
URPOSE: Today, the majority of medical graduates in countries such as the UK, the US or Germany are female. This poses a major problem for workforce planning especially in urology. We here use first the first time the previously established Brüggmann Groneberg (BG) index to assess if female academic career options advance in urology.
METHODS: Different operating parameters (student population, urology specialist population, urology chair female:male (f:m) ratio) were collected from the Federal Office of Statistics, the Federal Chamber of Physicians and the medical faculties of 36 German universities. Four time points were monitored (2000, 2005, 2010 and 2015). From these data, female to male (f:m) ratios and the recently established career advancement (BG) index have been calculated.
RESULTS: The German hospital urology specialists' f:m ratios were 0.257 (499 female vs. 1944 male) for 2015, 0.195 for 2010, 0.133 for 2005 and 0.12 for 2000. The career advancement (BG) index was 0.0007 for 2000, 0,0005 for 2005, 0.094 for 2010 and 0.073 for 2015. The decrease from 2010 to 2015 was due to an increase in the f:m ratio of hospital urologists and female medical students.
CONCLUSION: The BG index clearly illustrated that there is an urgent need for special academic career funding programs to counteract gender problems in urology. The BG index has been shown to be an excellent tool to assess female academic career options and will be very helpful to assess and document positive or negative changes in the next decades.
BACKGROUND: Although phosphodiesterase-4 (PDE4) inhibitors have been shown to reduce COPD exacerbation rate, their biological mechanism of action is not completely elucidated at the molecular level. We aimed to characterise the whole genome gene expression profile of the inhaled PDE4-inhibitor CHF6001 on top of triple therapy in sputum cells and whole blood of patients with COPD and chronic bronchitis.
METHODS: Whole genome gene expression analysis was carried out by microarray in 54 patients before and after 32 days treatment with CHF6001 800 and 1600 μg and placebo twice daily (BID) in a randomised crossover study.
RESULTS: CHF6001 had a strong effect in sputum, with 1471 and 2598 significantly differentially-expressed probe-sets relative to placebo (p-adjusted for False Discovery Rate < 0.05) with 800 and 1600 μg BID, respectively. Functional enrichment analysis showed significant modulation of key inflammatory pathways involved in cytokine activity, pathogen-associated-pattern-recognition activity, oxidative stress and vitamin D with associated inhibition of downstream inflammatory effectors. A large number of pro-inflammatory genes coding for cytokines and matrix-metalloproteinases were significantly differentially expressed for both doses; the majority (> 87%) were downregulated, including macrophage inflammatory protein-1-alpha and 1-beta, interleukin-27-beta, interleukin-12-beta, interleukin-32, tumour necrosis factor-alpha-induced-protein-8, ligand-superfamily-member-15, and matrix-metalloproteinases-7,12 and 14. The effect in blood was not significant.
CONCLUSIONS: Inhaled PDE4 inhibition by CHF6001 on top of triple therapy in patients with COPD and chronic bronchitis significantly modulated key inflammatory targets and pathways in the lung but not in blood. Mechanistically these findings support a targeted effect in the lung while minimising unwanted systemic class-effects.
TRIAL REGISTRATION: ClinicalTrial.gov, EudraCT, 2015-005550-35. Registered 15 July 2016.
Biofabrication of SDF-1 functionalized 3D-printed cell-free scaffolds for bone tissue regeneration
(2020)
Large segmental bone defects occurring after trauma, bone tumors, infections or revision surgeries are a challenge for surgeons. The aim of our study was to develop a new biomaterial utilizing simple and cheap 3D-printing techniques. A porous polylactide (PLA) cylinder was printed and functionalized with stromal-derived factor 1 (SDF-1) or bone morphogenetic protein 7 (BMP-7) immobilized in collagen type I. Biomechanical testing proved biomechanical stability and the scaffolds were implanted into a 6 mm critical size defect in rat femur. Bone growth was observed via x-ray and after 8 weeks, bone regeneration was analyzed with µCT and histological staining methods. Development of non-unions was detected in the control group with no implant. Implantation of PLA cylinder alone resulted in a slight but not significant osteoconductive effect, which was more pronounced in the group where the PLA cylinder was loaded with collagen type I. Addition of SDF-1 resulted in an osteoinductive effect, with stronger new bone formation. BMP-7 treatment showed the most distinct effect on bone regeneration. However, histological analyses revealed that newly formed bone in the BMP-7 group displayed a holey structure. Our results confirm the osteoinductive character of this 3D-biofabricated cell-free new biomaterial and raise new options for its application in bone tissue regeneration.
Hepatocellular carcinoma (HCC) shows a remarkable heterogeneity and is recognized as a chemoresistant tumor with dismal prognosis. In previous studies, we observed significant alterations in the serum sphingolipids of patients with HCC. This study aimed to investigate the in vitro effects of sorafenib, which is the most widely used systemic HCC medication, on the sphingolipid pathway as well as the effects of inhibiting the sphingolipid pathway in HCC. Huh7.5 and HepG2 cells were stimulated with sorafenib, and inhibitors of the sphingolipid pathway and cell proliferation, viability, and concentrations of bioactive metabolites were assessed. We observed a significant downregulation of cell proliferation and viability and a simultaneous upregulation of dihydroceramides upon sorafenib stimulation. Interestingly, fumonisin B1 (FB1) and the general sphingosine kinase inhibitor SKI II were able to inhibit cell proliferation more prominently in HepG2 and Huh7.5 cells, whereas there were no consistent effects on the formation of dihydroceramides, thus implying an involvement of distinct metabolic pathways. In conclusion, our study demonstrates a significant downregulation of HCC proliferation upon sorafenib, FB1, and SKI II treatment, whereas it seems they exert antiproliferative effects independently from sphingolipids. Certainly, further data would be required to elucidate the potential of FB1 and SKI II as putative novel therapeutic targets in HCC.
Requirements analysis and specification for a molecular tumor board platform based on cBioPortal
(2020)
Clinicians in molecular tumor boards (MTB) are confronted with a growing amount of genetic high-throughput sequencing data. Today, at German university hospitals, these data are usually handled in complex spreadsheets from which clinicians have to obtain the necessary information. The aim of this work was to gather a comprehensive list of requirements to be met by cBioPortal to support processes in MTBs according to clinical needs. Therefore, oncology experts at nine German university hospitals were surveyed in two rounds of interviews. To generate an interview guideline a scoping review was conducted. For visual support in the second round, screenshot mockups illustrating the requirements from the first round were created. Requirements that cBioPortal already meets were skipped during the second round. In the end, 24 requirements with sometimes several conceivable options were identified and 54 screenshot mockups were created. Some of the identified requirements have already been suggested to the community by other users or are currently being implemented in cBioPortal. This shows, that the results are in line with the needs expressed by various disciplines. According to our findings, cBioPortal has the potential to significantly improve the processes and analyses of an MTB after the implementation of the identified requirements.
Introduction: Reliable and cost-effective diagnostics for hepatitis E virus (HEV) infection are necessary. The aim of our study was to investigate which diagnostic test is most accurate to detect HEV infection in immunocompetent and immunosuppressed patients in a real world setting. Patients and Methods: We performed a retrospective analysis of 1165 patients tested for HEV antibodies and HEV PCR at the same time point. Clinical, laboratory and virological data were taken from patient charts. HEV IgA was measured in a subgroup of 185 patients. Results: HEV RNA was detectable in 61 patients (5.2%); most of them (n = 49, 80.3%/n = 43, 70.5%) were HEV IgM+ and IgG+; however, 12 patients (19.6%) were HEV RNA positive/HEV IgM negative and 17 patients (27.8%) were HEV RNA positive/HEV IgG negative. Ten HEV RNA positive patients (16.4%) had neither HEV IgG nor IgM antibodies. Importantly, all of them were immunosuppressed. HEV IgA testing was less sensitive than HEV IgM for HEV diagnosis. Conclusions: HEV infection can be overlooked in patients without HEV specific antibodies. Performing PCR is necessary to diagnose or exclude HEV infection in immunocompromised hosts. In immunocompetent patients, a screening based on HEV antibodies (IgG/IgM) is sufficient.
The efficacy of cisplatin-based chemotherapy in ovarian cancer is often limited by the development of drug resistance. In most ovarian cancer cells, cisplatin activates extracellular signal-regulated kinase1/2 (ERK1/2) signalling. Phosphoprotein enriched in astrocytes (PEA-15) is a ubiquitously expressed protein, capable of sequestering ERK1/2 in the cytoplasm and inhibiting cell proliferation. This and other functions of PEA-15 are regulated by its phosphorylation status. In this study, the relevance of PEA-15 phosphorylation state for cisplatin sensitivity of ovarian carcinoma cells was examined. The results of MTT-assays indicated that overexpression of PEA-15AA (a non-phosphorylatable variant) sensitised SKOV-3 cells to cisplatin. Phosphomimetic PEA-15DD did not affect cell sensitivity to the drug. While PEA-15DD facilitates nuclear translocation of activated ERK1/2, PEA-15AA acts to sequester the kinase in the cytoplasm as shown by Western blot. Microarray data indicated deregulation of thirteen genes in PEA-15AA-transfected cells compared to non-transfected or PEA-15DD-transfected variants. Data derived from The Cancer Genome Atlas (TCGA) showed that the expression of seven of these genes including EGR1 (early growth response protein 1) and FLNA (filamin A) significantly correlated with the therapy outcome in cisplatin-treated cancer patients. Further analysis indicated the relevance of nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signalling for the favourable effect of PEA-15AA on cisplatin sensitivity. The results warrant further evaluation of the PEA-15 phosphorylation status as a potential candidate biomarker of response to cisplatin-based chemotherapy.
Short linear motifs (SLiMs) located in disordered regions of multidomain proteins are important for the organization of protein–protein interaction networks. By dynamic association with their binding partners, SLiMs enable assembly of multiprotein complexes, pivotal for the regulation of various aspects of cell biology in higher organisms. Despite their importance, there is a paucity of molecular tools to study SLiMs of endogenous proteins in live cells. LC3 interacting regions (LIRs), being quintessential for orchestrating diverse stages of autophagy, are a prominent example of SLiMs and mediate binding to the ubiquitin-like LC3/GABARAP family of proteins. The role of LIRs ranges from the posttranslational processing of their binding partners at early stages of autophagy to the binding of selective autophagy receptors (SARs) to the autophagosome. In order to generate tools to study LIRs in cells, we engineered high affinity binders of LIR motifs of three archetypical SARs: OPTN, p62, and NDP52. In an array of in vitro and cellular assays, the engineered binders were shown to have greatly improved affinity and specificity when compared with the endogenous LC3/GABARAP family of proteins, thus providing a unique possibility for modulating LIR interactions in living systems. We exploited these novel tools to study the impact of LIR inhibition on the fitness and the responsiveness to cytarabine treatment of THP-1 cells – a model for studying acute myeloid leukemia (AML). Our results demonstrate that inhibition of LIR of a single autophagy receptor is insufficient to sensitize the cells to cytarabine, while simultaneous inhibition of three LIR motifs in three distinct SARs reduces the IC50 of the chemotherapeutic.
Background and Aims: Monocyte chemotactic protein-1 (MCP-1) is a potent chemoattractant for monocytes. It is involved in pathogenesis of several inflammatory diseases. Hepatic MCP-1 is a readout of macrophage activation. While inflammation is a major driver of liver disease progression, the origin and role of circulating MCP-1 as a biomarker remains unclear.
Methods: Hepatic CC-chemokine ligand 2 (CCL2) expression and F4/80 staining for Kupffer cells were measured and correlated in a mouse model of chronic liver disease (inhalative CCl4 for 7 weeks). Next, hepatic RNA levels of CCL2 were measured in explanted livers of 39 patients after transplantation and correlated with severity of disease. Changes in MCP-1 were further evaluated in a rat model of experimental cirrhosis and acute-on-chronic liver failure (ACLF). Finally, we analyzed portal and hepatic vein levels of MCP-1 in patients receiving transjugular intrahepatic portosystemic shunt insertion for complications of portal hypertension.
Results: In this mouse model of fibrotic hepatitis, hepatic expression of CCL2 (P = 0.009) and the amount of F4/80 positive cells in the liver (P < 0.001) significantly increased after induction of hepatitis by CCl4 compared to control animals. Moreover, strong correlation of hepatic CCL2 expression and F4/80 positive cells were seen (P = 0.023). Furthermore, in human liver explants, hepatic transcription levels of CCL2 correlated with the MELD score of the patients, and thus disease severity (P = 0.007). The experimental model of ACLF in rats revealed significantly higher levels of MCP-1 plasma (P = 0.028) and correlation of hepatic CCL2 expression (R = 0.69, P = 0.003). Particularly, plasma MCP-1 levels did not correlate with peripheral blood monocyte CCL2 expression. Finally, higher levels of MCP-1 were observed in the hepatic compared to the portal vein (P = 0.01) in patients receiving TIPS. Similarly, a positive correlation of MCP-1 with Child-Pugh score was observed (P = 0.018). Further, in the presence of ACLF, portal and hepatic vein levels of MCP-1 were significantly higher compared to patients without ACLF (both P = 0.039).
Conclusion: Circulating levels of MCP-1 mainly derive from the injured liver and are associated with severity of liver disease. Therefore, liver macrophages contribute significantly to disease progression. Circulating MCP-1 may reflect the extent of hepatic macrophage activation.
Background: Previously, we used inhibitors blocking BET bromodomain binding proteins (BRDs) in Ewing sarcoma (EwS) and observed that long term treatment resulted in the development of resistance. Here, we analyze the possible interaction of BRD4 with cyclin-dependent kinase (CDK) 9. Methods: Co-immunoprecipitation experiments (CoIP) to characterize BRD4 interaction and functional consequences of inhibiting transcriptional elongation were assessed using drugs targeting of BRD4 or CDK9, either alone or in combination. Results: CoIP revealed an interaction of BRD4 with EWS-FLI1 and CDK9 in EwS. Treatment of EwS cells with CDKI-73, a specific CDK9 inhibitor (CDK9i), induced a rapid downregulation of EWS-FLI1 expression and block of contact-dependent growth. CDKI-73 induced apoptosis in EwS, as depicted by cleavage of Caspase 7 (CASP7), PARP and increased CASP3 activity, similar to JQ1. Microarray analysis following CDKI-73 treatment uncovered a transcriptional program that was only partially comparable to BRD inhibition. Strikingly, combined treatment of EwS with BRD- and CDK9-inhibitors re-sensitized cells, and was overall more effective than individual drugs not only in vitro but also in a preclinical mouse model in vivo. Conclusion: Treatment with BRD inhibitors in combination with CDK9i offers a new treatment option that significantly blocks the pathognomonic EWS-ETS transcriptional program and malignant phenotype of EwS.
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)