Refine
Has Fulltext
- yes (810)
Year of publication
- 2022 (810) (remove)
Document Type
- Journal article (810) (remove)
Language
- English (810) (remove)
Keywords
- COVID-19 (16)
- machine learning (11)
- SARS-CoV-2 (10)
- heart failure (10)
- prostate cancer (10)
- inflammation (9)
- virtual reality (9)
- 3D printing (8)
- Germany (8)
- cancer (8)
- depression (8)
- remote sensing (8)
- total knee arthroplasty (8)
- theranostics (7)
- therapy (7)
- artificial intelligence (6)
- biodiversity (6)
- children (6)
- deep learning (6)
- glioblastoma (6)
- ischemic stroke (6)
- kinematic alignment (6)
- land use (6)
- radioligand therapy (6)
- radiotherapy (6)
- stroke (6)
- PSMA (5)
- Parkinson’s disease (5)
- Sentinel-2 (5)
- blood–brain barrier (5)
- boron (5)
- breast cancer (5)
- fluorescence (5)
- immunohistochemistry (5)
- melanoma (5)
- microRNA (5)
- multiple myeloma (5)
- neurodegeneration (5)
- pain (5)
- quality of life (5)
- DNA damage (4)
- GFAP (4)
- PET (4)
- anxiety (4)
- aromaticity (4)
- biomarker (4)
- catalysis (4)
- cell death (4)
- classification (4)
- conservation (4)
- education (4)
- embodiment (4)
- fibrosis (4)
- forest (4)
- gynecology (4)
- mental health (4)
- metabolomics (4)
- neuroinflammation (4)
- oxidative stress (4)
- periodontitis (4)
- pharmacokinetics (4)
- physical activity (4)
- prediction (4)
- surgery (4)
- time series (4)
- Alps (3)
- Alzheimer’s disease (3)
- Aspergillus (3)
- CXCR4 (3)
- Covid-19 (3)
- Fabry disease (3)
- Google Earth Engine (3)
- NDVI (3)
- PET/CT (3)
- T cells (3)
- active zone (3)
- additive manufacturing (3)
- adolescents (3)
- animal model (3)
- antimicrobial resistance (3)
- apoptosis (3)
- astrocytoma (3)
- biomarkers (3)
- blood-brain barrier (3)
- circadian clock (3)
- climate (3)
- climate change (3)
- cytokines (3)
- earth observation (3)
- extracellular matrix (3)
- gene expression (3)
- hippocampus (3)
- hyaluronic acid (3)
- immunotherapy (3)
- induced pluripotent stem cells (3)
- liver (3)
- long-term outcome (3)
- macrophages (3)
- magnetic resonance imaging (3)
- mass spectrometry (3)
- melt electrospinning writing (3)
- melt electrowriting (3)
- meta-analysis (3)
- metabarcoding (3)
- middle cerebral artery occlusion (3)
- myofibroblast (3)
- nephrotoxicity (3)
- neuropathic pain (3)
- nutrition (3)
- obesity (3)
- perylene bisimide (3)
- prognosis (3)
- radial (3)
- reactive oxygen species (3)
- recombination (3)
- reoperation (3)
- singlet oxygen (3)
- stemness (3)
- stress (3)
- teaching (3)
- toxicity (3)
- vitamin D (3)
- water oxidation (3)
- ACTH (2)
- AKT (2)
- ARONJ (2)
- Achilles (2)
- B-cell lymphoma (2)
- C-X-C motif chemokine receptor 4 (2)
- CADe (2)
- CRISPR/Cas9 (2)
- CT (2)
- Cushing’s syndrome (2)
- DNA (2)
- EAE (2)
- EBV (2)
- ERK1/2 (2)
- Escherichia coli (2)
- HSC (2)
- HUVEC (2)
- Landsat (2)
- MRI (2)
- NAFLD (2)
- NASH (2)
- NSSI (2)
- PSMA I&T (2)
- PSMA-RADS (2)
- Parkinson's disease (2)
- PlanetScope (2)
- RKIP (2)
- RNA sequencing (2)
- SOAT1 (2)
- STR profile (2)
- SUV (2)
- TNF (2)
- TNF-α (2)
- Trypanosoma (2)
- USP28 (2)
- X-ray (2)
- X-ray crystallography (2)
- [68Ga]PentixaFor (2)
- adolescence (2)
- adrenocortical carcinoma (2)
- adverse events (2)
- age (2)
- agriculture (2)
- altitudinal gradients (2)
- anaemia (2)
- anastomotic leakage (2)
- angiogenesis (2)
- annulation (2)
- arthropods (2)
- aspiration (2)
- asthma (2)
- autophagy (2)
- azulene (2)
- bats (2)
- bias correction (2)
- biofabrication (2)
- blood (2)
- body weight modification (2)
- body weight perception (2)
- bone marrow edema (2)
- bone marrow immune-microenvironment (2)
- bone regeneration (2)
- boronate (2)
- caloric restriction (2)
- cancer metabolism (2)
- cancer stem cells (2)
- cardiac (2)
- caries (2)
- caspase-3 (2)
- cell of origin (2)
- channelrhodopsin (2)
- chemotherapy (2)
- cholestasis (2)
- chondrogenic differentiation (2)
- cisplatin (2)
- cochlear implant (2)
- cohort studies (2)
- colonoscopy (2)
- comparison (2)
- computed tomography (2)
- coping (2)
- critically ill (2)
- cuticular hydrocarbons (2)
- cytokinins (2)
- decellularization (2)
- dementia (2)
- diabetes (2)
- diabetic nephropathy (2)
- diagnosis (2)
- diagnostics (2)
- double intentionality (2)
- drought (2)
- drug resistance (2)
- dual-stage crosslinking (2)
- dystonia (2)
- ecosystem function (2)
- ecosystem services (2)
- editorial (2)
- endoluminal (2)
- endoradiotherapy (2)
- endovascular (2)
- epidemiology (2)
- evaluation (2)
- evolution (2)
- fMRI (2)
- fibromyalgia syndrome (2)
- food safety (2)
- food security (2)
- foraging (2)
- forest management (2)
- fracture (2)
- functional diversity (2)
- fused deposition modeling (FDM) (2)
- genetic diagnostics (2)
- gingivitis (2)
- global change (2)
- glycoprotein VI (2)
- grassland (2)
- head and neck cancer (2)
- healthcare (2)
- heart (2)
- hepatic stellate cell (2)
- herpesvirus (2)
- hydrogels (2)
- hydrology (2)
- hypercortisolism (2)
- immersion (2)
- immune checkpoint blockade (2)
- immunosuppression (2)
- in vitro (2)
- in vivo imaging (2)
- individual differences (2)
- individual‐based model (2)
- inflammasome (2)
- influenza (2)
- insect monitoring (2)
- intensive care (2)
- intervention (2)
- ischemia (2)
- knee (2)
- landscape metrics (2)
- laterality (2)
- luminescence (2)
- lung cancer (2)
- mechanical thrombectomy (2)
- meiosis (2)
- metastasis (2)
- miRNA (2)
- mice (2)
- microbial spectrum (2)
- microclimate (2)
- microglia (2)
- mitochondria (2)
- molecular beam epitaxy (2)
- mortality (2)
- motivated reasoning (2)
- mouse model (2)
- multiple sclerosis (2)
- mutation (2)
- myocardial infarction (2)
- nanoparticles (2)
- national park (2)
- natural disturbance (2)
- navigation (2)
- negative pressure (2)
- neuroanatomy (2)
- neuroethology (2)
- neurofilament light chain (2)
- neurofilaments (2)
- octopamine (2)
- oncology (2)
- optogenetics (2)
- organic chemistry (2)
- organoids (2)
- osteoarthritis (2)
- osteogenesis (2)
- osteonecrosis of the jaw (2)
- osteoradionecrosis (2)
- outcome (2)
- outcomes research (2)
- ovarian cancer (2)
- pancreatic cancer (2)
- paraspeckles (2)
- pediatric (2)
- pelvic examination (2)
- pelvic palpation (2)
- phenotype (2)
- phosphorescence (2)
- photocatalysis (2)
- photoelectron spectroscopy (2)
- photoinduced electron transfer (2)
- phylogeny (2)
- physical fitness (2)
- physical health (2)
- plasma (2)
- platelet (2)
- platelets (2)
- polycycles (2)
- polycyclic aromatic hydrocarbons (2)
- posture (2)
- precision medicine (2)
- pregnancy (2)
- preterm infants (2)
- prevalence (2)
- proteomics (2)
- psychology (2)
- quality assurance (2)
- radiomics (2)
- rectal cancer (2)
- refractory (2)
- regulatory T cells (2)
- reliability (2)
- resilience (2)
- resonant tunneling diode (2)
- reverse shoulder arthroplasty (2)
- review (2)
- revision (2)
- salvage radiotherapy (2)
- schizophrenia (2)
- scleroderma (2)
- secondary structure (2)
- seroprevalence (2)
- shear stress (2)
- simulation (2)
- social anxiety (2)
- spinal muscular atrophy (2)
- stress resilience (2)
- subarachnoid hemorrhage (2)
- survival (2)
- sympathetic nervous system (2)
- synaptonemal complex (2)
- systematic review (2)
- systemic sclerosis (2)
- temozolomide (2)
- thermogenesis (2)
- thin films (2)
- thinking (2)
- tinnitus (2)
- tissue engineering (2)
- tomography (2)
- troponin (2)
- tumor necrosis factor (TNF) (2)
- user experience (2)
- vacuum-assisted closure (2)
- virtual environments (2)
- vision (2)
- visualization (2)
- vulnerability curve (2)
- 1,4-Diborabenzene (1)
- 177Lu (1)
- 18S (1)
- 2-DG (1)
- 2-deoxy-D-glucose (1)
- 26S proteasome (1)
- 2D-perfusion angiography (1)
- 360° videos (1)
- 3D GIS analysis (1)
- 3D analysis (1)
- 3D conformal silicone bolus (1)
- 3D ex vivo models (1)
- 3D lung tumor tissue models (1)
- 3D model generation (1)
- 3D model systems (1)
- 3D models (1)
- 3D printer (1)
- 3D scaffolds (1)
- 3D tissue model (1)
- 3D-conformal radiotherapy (1)
- 3D-printed tooth (1)
- 4-dimethylamino-4′-cyanodiphenylacetylene (1)
- 5-HT receptors (1)
- 5-methylcytosine (1)
- 6S RNA (1)
- A375 (1)
- A549 cell line (1)
- AAA+ ATPase p97 (1)
- ACC (1)
- ACE inhibitor (1)
- ACKR4 (1)
- AD mouse modele (1)
- AD pathogenesis (1)
- AD-AID (1)
- ADAM10 (1)
- ADP-ribosyltransferases (1)
- AI (1)
- AICDA (1)
- AID-ΔE4a (1)
- AIE (1)
- AIModules (1)
- ALS (1)
- AMADEUS (1)
- AMD (1)
- AMPK (1)
- APERIO (1)
- APERIO Hybrid (1)
- APEX2 (1)
- API (1)
- ARDS (1)
- ASC (1)
- ATF6 (1)
- ATG7 (1)
- ATM (1)
- AVA (1)
- A\(_{2A}\) adenosine receptor antagonist (1)
- AldoA (1)
- Alkekengi (1)
- Alkyl(amino)carbene (1)
- Alpelisib (1)
- Altenpflege (1)
- Alzheimer's diseas (1)
- Alzheimer’s dementia (1)
- Antiparanodal Autoantibodies (1)
- Apis dorsata (1)
- Apple Watch 7 (1)
- Arp2/3 complex (1)
- Atherosclerosis, intracranial arteries (1)
- Available soil water capacity (1)
- B cell culture (1)
- B7-H1 Antigen (1)
- BDG (1)
- BDNF (1)
- BDNF stimulation (1)
- BET Inhibitor (1)
- BN compounds (1)
- BRAF mutation (1)
- BRD4 (1)
- BTN2A1 (1)
- BTN3A1 (1)
- BT_1884 (1)
- BacT/ALERT (1)
- Background Epithelioid haemangioma (1)
- Bartak (1)
- Barth syndrome (1)
- Bayesian inverse problems (1)
- Bernstein-type inequality (1)
- Beta-blocker (1)
- Bethe–Salpeter equation (1)
- Bi-Fidelity method (1)
- Bialowieza (1)
- Big Five (1)
- Bismuth (1)
- Black Scholes equation (1)
- Bland–Altman (1)
- Bloom setting (1)
- Bodenwasser (1)
- Boranes (1)
- Boron (1)
- Braak (1)
- Brain atrophy (1)
- Brain–computer interfaces (BCI) (1)
- Brassicogethes spp. (1)
- Buche (1)
- CA19-9 (1)
- CA3 (1)
- CA4 (1)
- CAPA (1)
- CAPS (1)
- CD105 (1)
- CD133 (1)
- CD147 (1)
- CD274 (1)
- CD40 (1)
- CD40L (1)
- CD44 (1)
- CD8 T cell (1)
- CD95 (1)
- CLIP (1)
- CMR (1)
- CNS cancer (1)
- CNS disorders (1)
- CNS imaging (1)
- COPD (1)
- COVID-19 pandemic (1)
- COVID-19 testing (1)
- COVID‐19 (1)
- COVID‐19 vaccination (1)
- CPF (1)
- CRC (1)
- CRH stimulation test (1)
- CRISPR (1)
- CRPS (1)
- CRY evolution (1)
- CSVD (1)
- CTCAE (1)
- CTLA-4 (1)
- CTLA-4 Antigen (1)
- CX5461 (1)
- CXCL4 (1)
- CXCL7 (1)
- CXCR4-targeting (1)
- CYP24A1 (1)
- Ca2+ homeostasis (1)
- Ca2+ ion analysis (1)
- Ca2+ leak (1)
- Ca2+ oscillation (1)
- Ca\(^{2+}\)-Imaging (1)
- Campylobacter jejuni (1)
- Candida albicans (1)
- Candida auris (1)
- Carbon Monoxide (1)
- Carbon-11 (1)
- CardioMEMS™ HF-System (1)
- Care-Arbeit (1)
- Carleson embedding theorem (1)
- Cdc48 (1)
- Cell Index (1)
- Central Asia (1)
- Chagas disease (1)
- China (1)
- Chl (1)
- Chlamydia (1)
- Chlamydia trachomatis (1)
- CholinomiRs (1)
- Chorioamnionitis (1)
- Chromophore Assembly (1)
- Chronic heart failure (1)
- Cisplatin (1)
- ClearSight\(^®\) (1)
- Climatic water balance (1)
- Clinical Neuroradiology (1)
- Clostridioides binary toxins (1)
- Cochlear duct length (1)
- Cochlear planning software (1)
- Cognitive decline (1)
- Colombia (1)
- Compound 3k (1)
- Corannulene (1)
- Covid‐19 (1)
- CreERT2 (1)
- Crohn disease (1)
- Crohn's disease (1)
- Crohn’s disease (1)
- Cu(111) (1)
- Cushing (1)
- Cushing syndrome (1)
- Cushing's (1)
- Cushing's disease (1)
- Cx3cr1 (1)
- Cyclooxygenase-2 (1)
- Cyclophilin A (1)
- DASA-58 (1)
- DIA-MS (1)
- DNA helicase (1)
- DNA repair (1)
- DNA replication (1)
- DNA sensing (1)
- DNA storage (1)
- DNA-PK (1)
- DNA-repair (1)
- DNA/RNA binding (1)
- DNA/RNA sensors (1)
- DSA (1)
- DSB damage (1)
- DUB (1)
- Dara-KDT-P(A)CE (1)
- Dark Factor of Personality (1)
- Deep learning (1)
- Denoising (1)
- Der p 23 (1)
- Deutsche Forschungsgemeinschaft (1)
- Diabetes mellitus (1)
- Dictyota (1)
- Dictyotaceae (1)
- Dirac points (1)
- Direct care workers (1)
- Dociostaurus maroccanus (1)
- Drug Therapy, Combination (1)
- Duchenne muscular dystrophy (1)
- E-H bond activation (1)
- EANM dosage card (1)
- ECM remodeling (1)
- EEG (1)
- EEOS (1)
- EHT1864 (1)
- EMMPRIN (1)
- EMT (1)
- EO data (1)
- EPR spectroscopy (1)
- ER Ca2+ imaging (1)
- ER Ca2+ store (1)
- ER stress (1)
- EU-RHAB registry (1)
- Earth Observation (1)
- Edmund Husserl (1)
- Embolism resistance (1)
- Emotional labor (1)
- Emotionsregulation (1)
- Enterobacteriaceae (1)
- Enzymes (1)
- FADS (1)
- FCS (1)
- FDM (1)
- FGF-pathway (1)
- FGFR (1)
- FGFR-inhibitors (1)
- FGFR1 (1)
- FIB-4 (1)
- FLIMbee (1)
- FRG (1)
- FRG calculations (1)
- Fabry Disease (FD) (1)
- Fabry genotype (1)
- Fabry phenotype (1)
- FcγR receptor (1)
- Fibromyalgia (1)
- Fibromyalgia syndrome (1)
- Filial piety/xiao (1)
- Fisher Z-score transformation (1)
- Fitbit Sense (1)
- Flt3L (1)
- FluidFM technology (1)
- Fluorescence Microscopy (1)
- Fn14 (1)
- FoxO3 (1)
- Foxp3 (1)
- G-protein-coupled receptors (1)
- G3BP (1)
- GABA\(_A\) (1)
- GABA\(_{A}\) receptors (1)
- GATA-3 (1)
- GFAP-astrocytopathies (1)
- GIS-analysis (1)
- GLDN variant (1)
- GLP-1 (1)
- GPCR (1)
- GPCRs (1)
- GPVI (1)
- GPVI shedding (1)
- GapN (1)
- Garmin Fenix 6 Pro (1)
- Gb3 and lyso-Gb3 biomarkers (1)
- German Hepatitis C-Registry (1)
- German Research Foundation (1)
- German/French/Italian (1)
- Gerontologie (1)
- GibS (1)
- Gleason score (1)
- Glial fibrillary acidic protein (1)
- Glioblastoma (1)
- Glioma stem cells (1)
- Google Earth (1)
- Government research funding (1)
- Greenland (1)
- Guillain-Barré syndrome (1)
- GvHD (1)
- H7N9 influenza virus (1)
- HBMEC (1)
- HCV infection (1)
- HD (1)
- HDBSCAN (1)
- HGPS (1)
- HHV-6 (1)
- HNSCC (1)
- HPV (1)
- HPc (1)
- Hamman's syndrome (1)
- Hans algorithm (1)
- Hegyi competition index (1)
- Helicobacter pylori (1)
- HiGHmed (1)
- Himalaya Karakoram (1)
- Hippo signaling (1)
- Hodgkin lymphoma (1)
- Htr1a (1)
- Htr2a (1)
- Htr2c (1)
- Hydraulic conductivity (1)
- Hydraulic plasticity (1)
- Hydrogen-deuterium (1)
- IABP (1)
- IACS (1)
- ICD-10 (1)
- ICF (1)
- ICRS (1)
- ICU staff (1)
- IDH (1)
- IDH1/2 (1)
- IGFBP2 (1)
- III–V semiconductor devices (1)
- IL-17A-inhibition (1)
- IL-6 (1)
- IL6 (1)
- IL‐10 (1)
- INR rebound (1)
- IR (1)
- ISBI (1)
- ITS2 (1)
- IgE (1)
- IgG (1)
- Ileal conduit (1)
- Ileum-Conduit (1)
- Image Aesthetic Assessment (1)
- In vitro toxicity testing (1)
- InSAR (1)
- Inclusion Rate (1)
- Indus-Ganges-Brahmaputra-Meghna (1)
- InteractionSuitcase (1)
- Interleukin-1 (1)
- Interleukin-4 (1)
- Internet of Things (1)
- IoT (1)
- Ire1 (1)
- JAQ1 (1)
- JIA (1)
- JQ1 (1)
- Jahn–Teller effect (1)
- Jena Experiment (1)
- J‐aggregates (1)
- KRAS biomarker signatures (1)
- KWIC (1)
- Klebsiella pneumoniae (1)
- Koenigs function (1)
- Kono-S anastomosis (1)
- L929 (1)
- LAMN (1)
- LASP1 (1)
- LC/MS (1)
- LCCS11 (1)
- LC–HRESIMS (1)
- LC–MS/MS (1)
- LGMDR5 (1)
- LI-rTMS (1)
- LIF (1)
- LMX (1)
- LND (1)
- LNE (1)
- LPS (1)
- Landsat archive (1)
- Landsat-8 (1)
- Laplace approximation (1)
- Large loop excision of the transformation zone (LLETZ) (1)
- Lewis acids (1)
- Li-Fraumeni syndrome (1)
- LiDAR (1)
- Lippert–Mataga plot (1)
- LoRaWAN (1)
- Long-term care (1)
- Loop electrosurgical excision procedure (LEEP) (1)
- Lymantria dispar (1)
- Lymph2Cx assay (1)
- M2 (1)
- M30 (1)
- MAP kinase pathway (1)
- MAP1B (1)
- MAS (1)
- MATQ-seq (1)
- MCC950 (1)
- ME/CFS (1)
- MEDAS (1)
- METTL8 (1)
- MGMT (1)
- MIBG (1)
- MIZ1 (1)
- MMP-1 (1)
- MMP9 (1)
- MNV type 3 (1)
- MOC fibers (1)
- MRONJ (1)
- MRSA (1)
- MRSA - methicillin-resistant Staphylococcus aureus (1)
- MSCT (1)
- MSCs (1)
- MTB (1)
- MTH1 (1)
- MTL30 (1)
- MTX (1)
- MUST-Score (1)
- MYC (1)
- Mactel 2 (1)
- Malaise trap (1)
- Mato Grosso (1)
- Medaka fish (1)
- Mekong (1)
- Memory dysfunction (1)
- Meniere’s disease (1)
- Merocyanine (1)
- Mesoarchaean (1)
- Metalloradicals (1)
- MiMIC (1)
- MitoQ (1)
- Mitochondrial Matrix Protein (1)
- Mitteleuropa (1)
- Modified Nucleotides in tRNAs (1)
- Modifizierte Sugarbaker-Technik (1)
- Monte Carlo (1)
- Mucopolysaccharidosis IIIa (1)
- Multiple myeloma (1)
- Munigua (1)
- Mwanza (1)
- Mycobacterium marinum (1)
- Mycobacterium tuberculosis (1)
- N-heterocyclic carbene (1)
- N-methylpyridinium pyrene (1)
- NADPH (1)
- NAKO (1)
- NAP-2 (1)
- NEAT1 (1)
- NF-kappa-B (1)
- NFAT (1)
- NFATc1 (1)
- NFkappaB (1)
- NFκB (1)
- NK cell (1)
- NLPHL (1)
- NLRP3 (1)
- NMR (1)
- NOAC (1)
- NONO (1)
- NPWT (1)
- NRAS mutation (1)
- NSCLC (1)
- NSG (1)
- NaV1.8 (1)
- Naphthylisoindolinone alkaloids (1)
- National Science Foundation (1)
- Neisseria gonorrhoeae (1)
- Nestin (1)
- NfL (1)
- Nicandra (1)
- Nickel ComplexCyclic (1)
- Nile Delta (Egypt) (1)
- Nodo-parandopathy (1)
- Northern Bald Ibis (1)
- Npy (1)
- Npyr1 (1)
- Npyr2 (1)
- Nucleic Acids (1)
- Nucleobase Analogue (1)
- ODE (1)
- OHIP-49 (1)
- ONJ (1)
- Ockham (1)
- Olea (1)
- Optical Music Recognition (1)
- Orai2 (1)
- Organelles (1)
- Orthoptera (1)
- Osteopontin (1)
- Oxford knee score (1)
- PBM (1)
- PCDHGC3 (1)
- PCL retention (1)
- PCa (1)
- PD-1 (1)
- PDE (1)
- PDE4-I (1)
- PEGylation (1)
- PET imaging (1)
- PET/MR systems (1)
- PETRI-seq (1)
- PF4 (1)
- PI3K (1)
- PIK3R1 (1)
- PKA (1)
- PKM2 (1)
- PMMA (1)
- PNA (peptide nucleic acid) (1)
- PP2A (1)
- PPGL (1)
- PRAME (1)
- PROM (1)
- PRRT (1)
- PSA (1)
- PSA response (1)
- PSMA PET/CT (1)
- PSMA-617 (1)
- PSMA-TV (1)
- PSMA‐617 (1)
- PTEN (1)
- PTSD (1)
- Paeonia (1)
- Parastomale Hernie (1)
- Parent Piano-Stool Complex (1)
- Parkinson (1)
- Pauli procedure (1)
- Pauli-Verfahren (1)
- Pearson correlation coefficient (1)
- Pelvisio® (1)
- Peter Singer (1)
- Pfam domain (1)
- Phaeophyceae (1)
- Physalis (1)
- Pnictogen reduction (1)
- PolSAR (1)
- Portland cement (1)
- Precipitation gradient (1)
- Professionalism (1)
- Programmed Cell Death 1 Receptor (1)
- QIVIVE (1)
- R-CHOP (1)
- R0 (1)
- RADS (1)
- RAP (1)
- RBM8A (1)
- RCT (1)
- RECK (1)
- REMO-iMOVE (1)
- RIM1α (1)
- RLT (1)
- RNA (1)
- RNA Methyltransferase (1)
- RNA interference (1)
- RNA secondary structure (1)
- RNA-binding proteins (1)
- RNAPOL1 (1)
- RNase III (1)
- ROI (1)
- ROS (1)
- RS-13 (1)
- RTPS1 (1)
- RTPS2 (1)
- RYGB (1)
- Rac1 (1)
- Raman micro-spectroscopy (1)
- Reciprocity (1)
- Rhizopus (1)
- Rho GTPase (1)
- Ribosomal protein gene (1)
- Rotary EXcitation (REX) (1)
- Roux-en-Y gastric bypass (1)
- Roux-en-Y gastric bypass surgery (1)
- Ruthenium complexes (1)
- Rv3034c (1)
- S100A8/S100A9 (1)
- SAMD3 (1)
- SAR (1)
- SARS‐CoV‐2 infection (1)
- SEM (1)
- SERCA (1)
- SF-12 (1)
- SF3 helicase (1)
- SGLT2 inhibitors (1)
- SIRT1 (1)
- SKY analysis (1)
- SLA (1)
- SMLM (1)
- SMN granules (1)
- SOC content prediction (1)
- SP-fixation (1)
- SPECT (1)
- SPECT Scanner (1)
- SSI (1)
- SSTR-RADS (1)
- STBS (1)
- STEM classroom (1)
- STEM education (1)
- STEM integration (1)
- STEMI (1)
- STORM (1)
- STS (1)
- SV pool (1)
- SWLS (1)
- Scarabaeidae (1)
- Schwann cell (1)
- Schwann cell differentiation (1)
- Scotus (1)
- Sentinel-1 (1)
- Sentinel-1 (S-1) synthetic aperture radar (SAR) (1)
- Sierra Nevada (1)
- Singhbhum Craton (1)
- Skin Neoplasms (1)
- Snow Line Elevation (1)
- Sodium-Glucose Cotransporters (SGLTs) (1)
- Southeast Asia (1)
- Staphylococcus (1)
- Supramolecular Element (1)
- Switzerland (1)
- Syk (1)
- T cell plasticity (1)
- T cell receptor (1)
- T-cell epitope (1)
- T-cells (1)
- T-shaped π-π stacking (1)
- T1rho (1)
- T1ρ (1)
- TD-DFT (1)
- TGF-β (1)
- TGFβ signaling (1)
- TH1579 (1)
- TH588 (1)
- TKA (1)
- TKI (1)
- TMEM43 (1)
- TNF alpha (1)
- TNF receptor 2 (TNFR2) (1)
- TNF receptor associated factor 1 and 2 (TRAF1, TRAF2) (1)
- TNF receptor associated factor 2 (TRAF2) (1)
- TNF-related apoptosis-inducing ligand (1)
- TNFR2 (1)
- TRRAP (1)
- TTFields (1)
- TTS (1)
- TT\(_{1rho}\) mapping (1)
- TWEAK (1)
- TXNIP (1)
- T\(_{1P}\) dispersion (1)
- T\(_{1P}\) mapping (1)
- T\(_{reg}\) and Foxp3 (1)
- Taita Hills (1)
- Takotsubo cardiomyopathy (1)
- Takotsubo syndrome (1)
- Tanzania (1)
- Th17 (1)
- Th17 cells (1)
- Townes (1)
- Treg (1)
- Tregs (regulatory T cells) (1)
- Trichternetz (IPST) (1)
- Trigona fuscipennis (1)
- Trypanosoma brucei gambiense (1)
- TspanC8 (1)
- Tumor Treating Fields (TTFields) (1)
- UAV (1)
- UMAP (1)
- Unc-13 (1)
- Uranium (1)
- Usher syndrome (1)
- V1–V9 (1)
- V4 (1)
- V7/V8 (1)
- VA-ECMO (1)
- VAC (1)
- VARS2 (1)
- VDR (1)
- VEGF (1)
- WNT (1)
- WNT signaling (1)
- Warburg effect (1)
- Western Europe (1)
- Withings ScanWatch (1)
- Wnt signaling (1)
- X-chromosomal inactivation (1)
- XAI (1)
- XBP1 (1)
- XLH (1)
- XNA (1)
- XPA (1)
- XR (1)
- XRPD (1)
- Xylem (1)
- Xylem vulnerability curve (1)
- Y chromosome degeneration (1)
- Y14 (1)
- YAP (1)
- YouTube (1)
- Zagros oak forests (1)
- ZfKD (1)
- Zosterops silvanus (1)
- [11C]-Choline PET/CT (1)
- [11C]-Methionine (1)
- [177Lu]/[90Y]PentixaTher (1)
- [177Lu]Lu-PSMA I&T (1)
- [177Lu]PentixaTher (1)
- [18F]FDG positron emission tomography (1)
- [90Y]PentixaTher (1)
- [99mTc]-Sestamibi scan (1)
- [\(^{68}\)Ga]Ga-FAPI (1)
- \(^{177}\)Lu (1)
- \(^{18}\)F-DCFPyL PET/CT (1)
- \(^{18}\)F-PSMA-1007 (1)
- \(^{1}\)H-\(^{13}\)C HETCOR (1)
- aPC (1)
- abandoned land (1)
- abdominal compartment syndrome (1)
- abdominal trauma (1)
- accelerated hyperfractionation (1)
- access (1)
- accuracy (1)
- acebutolol (1)
- acetylation (1)
- acetylsalicylic acid (1)
- acetyltransferase (1)
- achiasmatic (1)
- acid ceramidase inhibitor ceranib-2 (1)
- acid sphingomyelinase (1)
- acitretin (1)
- acoustic stream (1)
- acrylate-endcapped urethane-based polymer (AUP) (1)
- actin (1)
- action (1)
- action effects (1)
- action potential (1)
- action representation (1)
- activity (1)
- activity-dependent slowing (1)
- acute brain slices (1)
- acute hypobaric hypoxia (1)
- acute kidney injury (1)
- adalimumab (1)
- adaptation (1)
- adaptive tutoring (1)
- adhesion molecule (1)
- adipogenic differentiation (1)
- adrenal cancer (1)
- adrenal surgery (1)
- adrenalectomia (1)
- adrenocortical adenocarcinoma (1)
- adrenocortical adenoma (1)
- adrenocortical cancer (1)
- adrenocortical development (1)
- adrenocortical tumor (1)
- adrenocortical tumors (1)
- adsorption (1)
- adult learning (1)
- adult stem cells (1)
- adult-onset (1)
- advanced cutaneous squamous cell carcinoma (1)
- adverse drug reaction (1)
- adverse effects (1)
- adverse event (1)
- adverse outcome pathway (1)
- adverse outcome pathway (AOP) (1)
- aerobiology (1)
- aerodynamic drag reduction (1)
- affective appraisal (1)
- agar diffusion test (1)
- age stereotypes (1)
- age-related differentially methylated regions (ageDMRs) (1)
- age-related hearing loss (1)
- agency (1)
- aggregation (1)
- aging (1)
- agonist (1)
- agonistic antibodies (1)
- agri-environment scheme (1)
- agricultural drought (1)
- agricultural pests (1)
- agroforestry (1)
- aldolase A (1)
- alkyl halides (1)
- alkylideneborane (1)
- allergens (1)
- allergy (1)
- alloSCT patients (1)
- allometry (1)
- alpha diversity (1)
- alpine plants (1)
- altered fractionation (1)
- amino acid (1)
- amino acid restriction (1)
- ammonia borane (1)
- ampicillin (1)
- analgesic medication (1)
- anaphylaxis (1)
- anastomotic leak (1)
- anatomic shoulder arthroplasty (1)
- ancillary services (1)
- aneurysmal subarachnoid haemorrhage (1)
- angiogenesis inhibitors (1)
- angiography (1)
- anhedonia (1)
- animal behaviour (1)
- animal models (1)
- anion channel (1)
- anionic carbene (1)
- anions (1)
- ankle (1)
- anniversary (1)
- annotation (1)
- anorectal abscess (1)
- ant-colony optimization (1)
- anthocyanin (1)
- anthocyanins (1)
- anthropometric measurement (1)
- anthroposphere (1)
- anti-Parkinson agents (1)
- anti-bacterial agents (1)
- anti-hormonal therapy (1)
- anti-inflammatory agents (1)
- antibacterial drug resistance (1)
- antibiotic bone concentration (1)
- antibiotic elution (1)
- antibiotic prescribing quality (1)
- antibiotic resistance (1)
- antibiotics (1)
- antibodies (1)
- antibody fusion protein (1)
- antibody–drug conjugates (1)
- anticancer activity (1)
- anticoagulation (1)
- antidepressant (1)
- antigen testing (1)
- antimicrobial stewardship (1)
- antimony (1)
- antiphospholipid syndrome (1)
- antiresorptive drug-related osteonecrosis of the jaw (1)
- antitumor peptide (1)
- antiviral activity (1)
- anti‐SARS‐CoV‐2‐spike IgG (1)
- aortic dissection (1)
- apheresis technologies (1)
- apheresis-therapeutic (1)
- apis mellifera (1)
- aplastic anemia (1)
- apolipoprotein J (1)
- appearance (1)
- appendectomy (1)
- appendicitis (1)
- appendix (1)
- applied ethics (1)
- approach (1)
- approach-avoidance decisions (1)
- approach–avoidance (1)
- aquaporin (1)
- area‐concentrated search (1)
- arene-fluoroarene (1)
- aromatic amides (1)
- arrhythmogenesis (1)
- arrhythmogenic cardiomyopathy (1)
- arteriovenous extracorporeal hemadsorption technique (1)
- arteriovenous loop (1)
- arthritis (1)
- arthrography (1)
- arthrogryposis (1)
- arthropod predators (1)
- artificial base pair (1)
- artificial photosynthesis (1)
- aseptic loosening (1)
- ash dieback (1)
- aspirin (1)
- associative learning (1)
- astaxanthin (1)
- astrocytes (1)
- asymptotically flat ends (1)
- at-home sampling (1)
- atherosclerosis (1)
- atmospheric circulation (1)
- atomic layer deposition (1)
- atraumatic surgery (1)
- atrial fibrillation (1)
- attention capture (1)
- attention deficit/hyperactivity disorder (ADHD) (1)
- attitude of health personnel (1)
- atypical teratoid rhabdoid tumors (1)
- auction based task assignment (1)
- audiological services (1)
- authoring platform (1)
- autoantibodies (1)
- autobiographical memory (1)
- autoimmune (1)
- autoimmune disease (1)
- autoimmunity (1)
- autoinhibition (1)
- autoinjector (1)
- autologous hematopoietic stem cell transplantation (1)
- automation (1)
- autonomic nervous system (1)
- avatar embodiment (1)
- avatars (1)
- avoidable blood loss (1)
- awake prone positioning (1)
- axial alignment (1)
- axonopathy (1)
- azaborole (1)
- azido borane (1)
- background knowledge (1)
- backward orbit (1)
- bacterial (1)
- bacterial cellulose dressing (1)
- bacterial infection model (1)
- bacterial meningitis (1)
- bacterial pathogens (1)
- band structure (1)
- bargaining behavior (1)
- bark beetle disturbance (1)
- base of support (1)
- bee abundance (1)
- bee body size (1)
- bee decline (1)
- bee pollination (1)
- bee species richness (1)
- beech forests (1)
- beetle communities (1)
- behavior perception (1)
- behavioral experiments (1)
- beta diversity (1)
- beta-lactam (1)
- beta-oxidation (1)
- beta‐d‐glucan (1)
- biased signaling (1)
- bicommutators (1)
- bilberry (1)
- bile (1)
- binaural hearing (1)
- binding pocket (1)
- bioactivities (1)
- biochemical assays (1)
- bioconjugation (1)
- biodegradable (1)
- biodiversity exploratories (1)
- biodiversity–ecosystem functioning relationship (1)
- bioinformatics (1)
- bioink (1)
- biological activities (1)
- biologics (1)
- biomass (1)
- biomimetic tissue models (1)
- biophysics (1)
- bioprinting (1)
- biosensor (1)
- biosimilar (1)
- biosonar (1)
- biosphere (1)
- birds (1)
- birth cohort (1)
- birth hospitals (1)
- bisphenol A (1)
- bisphosphonates (1)
- bisulfite pyrosequencing (1)
- black currant (1)
- bladder cancer (1)
- bleeding on probing (1)
- blood contamination (1)
- blood flow (1)
- blood nerve barrier (1)
- blood pressure (1)
- blood processing (1)
- blood purification (1)
- blood stream infections (1)
- blood vessel (1)
- blood-brain barrier (BBB) model (1)
- bloodstream infection (1)
- blood–labyrinth barrier (1)
- body awareness (1)
- body image distortion (1)
- body image disturbance (1)
- body language (1)
- body mass index (BMI; kg/m\(^2\)) (1)
- body representation (1)
- body size (1)
- bonding (1)
- bone (1)
- bone biology (1)
- bone bruise (1)
- bone cement (1)
- bone defect (1)
- bone fractures (1)
- bone loss (1)
- bone marrow failure (1)
- bone marrow homing (1)
- bone marrow lesion/edema (1)
- bone marrow mesenchymal stromal cells (BM-MSCs) (1)
- bone marrow-derived monocytes (1)
- bone metastasis (1)
- bone model (1)
- bone morphogenetic protein 2 (BMP2) (1)
- bone morphology (1)
- bone replacement material (1)
- boolean in silico models (1)
- boracycle (1)
- boranes (1)
- boric acid (1)
- boronate esters (1)
- boronic acid (1)
- borylation (1)
- brain (1)
- brain cancer (1)
- brain development (1)
- brain disorders (1)
- brain endothelial cells (1)
- brain state (1)
- brain tumor (1)
- brain-metastasis (1)
- brain–liver chip (1)
- breakthrough infection (1)
- breast cancer metastases (1)
- breast cancer predisposition genes (1)
- breast neoplasms (1)
- brown seaweeds (1)
- bruxism (1)
- bulk-fill technique (1)
- bullous pemphigoid (1)
- bumblebees (1)
- buparlisib (1)
- burden (1)
- burned area (1)
- burst abdomen (1)
- butyrophilin (1)
- c-MYC (1)
- c-Myc (1)
- c-fos (1)
- c-reactive protein (1)
- cDC2 subset (1)
- cGMP (1)
- cable-clamp implants (1)
- cad-cam (1)
- calcium-magnesium phosphate cement (1)
- calipered (1)
- calprotectin (1)
- cancer care (1)
- cancer diagnosis (1)
- cancer dissemination (1)
- cancer predisposition (1)
- cancer prevention (1)
- candidemia (1)
- canonicalization (1)
- canopy cover loss (1)
- canopy herbivory (1)
- capsule endoscopy (1)
- carbene (1)
- carbon footprint (1)
- carbon nanotubes (1)
- carbonyl (1)
- carboxylation (1)
- cardiac MRI (1)
- cardiac catheterization/ intervention (1)
- cardiac implants (1)
- cardiac innervation imaging (1)
- cardiac magnetic resonance imaging (1)
- cardiac metabolism (1)
- cardiac morbidity (1)
- cardiac mortality (1)
- cardiac nerve (1)
- cardiac patch (1)
- cardiac thrombi (1)
- cardiac training group (1)
- cardioactive factor (1)
- cardiolipin (1)
- cardiomyocyte (1)
- cardiomyocytes (1)
- cardiomyopathy (1)
- cardiovascular diseases (1)
- cardiovascular drugs (1)
- cardiovascular genetics (1)
- cardiovascular magnetic resonance (CMR) (1)
- cardiovascular risk factors (1)
- career adaptability (1)
- career coping (1)
- career engagement (1)
- career satisfaction (1)
- cartilage (1)
- cartilage defect (1)
- cartilage regeneration (1)
- case report (1)
- catalyst (1)
- catalyst synthesis (1)
- catalytic mechanisms (1)
- caudate nucleus (1)
- causal networks (1)
- celecoxib (1)
- cell imaging (1)
- cell membrane model (1)
- cell rich blue nevus (1)
- cell-based therapies (1)
- cell-cell interactions (1)
- cellular inhibitor of apoptosis 1/2 (cIAP1/2) (1)
- cellular origin (1)
- cellular reprogramming (1)
- cement pastes (1)
- cemiplimab (1)
- central autonomic network (1)
- central complex (1)
- central venous catheter (1)
- centripetal technique (1)
- ceramics (1)
- ceramidase (1)
- ceramide (1)
- ceramides (1)
- cerebEND (1)
- cerebral vasospasm (1)
- cerebrospinal fluid (1)
- certifying algorithm (1)
- cervical dysplasia (1)
- chain cover (1)
- chalcidoid wasps (1)
- chalcogens (1)
- change detection (1)
- change vector analysis (1)
- channel management (1)
- characterization and analytical techniques (1)
- charge transfer (1)
- checkpoint inhibitor therapy (1)
- checkpoint inhibitors (1)
- chemical communication (1)
- chemical identifier (1)
- chemical mimicry (1)
- cheminformatics (1)
- chemokines (1)
- chemoradiotherapy (1)
- chenodeoxycholate (1)
- childhood (1)
- childhood cancer (1)
- chirality transfer (1)
- chitinase-3-like protein 1 (1)
- choanoflagellates (1)
- cholesterol metabolism (1)
- cholinergic system (1)
- chromatin (1)
- chromosome inversion (1)
- chronic heart failure (1)
- chronic kidney disease (1)
- chronic mesenteric ischemia (1)
- chronic musculoskeletal pain (1)
- chronic stress (1)
- chrysididae (1)
- circadian clock neurons (1)
- circularly polarized luminescence (1)
- circulation type (CT) (1)
- circulatory assist devices (1)
- citalopram (1)
- class II restoration (1)
- classical Hodgkin lymphoma (1)
- claudin-1 (1)
- click chemistry (1)
- climate change mitigation (1)
- climate changes (1)
- climate models (1)
- climatic factors (1)
- climatic gradients (1)
- clinical outcomes (1)
- clinical practice guideline (1)
- clinical routine data (1)
- clinical studies/trials (1)
- clinical trial (1)
- clinical trials (1)
- clock network (1)
- clusterin transporter (1)
- co-culture (1)
- coal mining area (1)
- coastal erosion (1)
- coastline dynamics (1)
- cochlea (1)
- cochlear implantation (1)
- cochlear implants (1)
- cocoa (1)
- cocrystallization (1)
- coexistence (1)
- cognitive (1)
- cognitive basis (1)
- cognitive conflict (1)
- cognitive control (1)
- cognitive decline (1)
- cognitive impairment (1)
- coherence (1)
- coherent anti-Stokes Raman scattering (CARS) microscopy (1)
- coherent multidimensional spectroscopy (1)
- cohort study (1)
- coisotropic reduction (1)
- cold stress (1)
- cold temperature (1)
- cold-shock protein (1)
- coleoptera (1)
- collaborative research (1)
- collagen (1)
- collision (1)
- colon resection (1)
- colony stimulating factor 1 (1)
- color perception (1)
- color-coding (1)
- colorectal cancer (1)
- colorectal carcinoma (1)
- combinatorial libraries (1)
- combined retinal dystrophy (1)
- common blue nevus (1)
- community structure (1)
- comorbid diseases (1)
- comparative sequence analysis (1)
- compensation (1)
- competition (1)
- complementary currencies (1)
- complex polynomials (1)
- complex regional pain syndrome (1)
- complication (1)
- complications (1)
- composite detection (1)
- composition of functions (1)
- compressed sensing (1)
- computational biology and bioinformatics (1)
- computational docking (1)
- computational modeling (1)
- computer software (1)
- condenser capacity (1)
- conditioned place preference (1)
- conference abstracts (1)
- confidence (1)
- confixes (1)
- confounders (1)
- congruence (1)
- congruency (1)
- conjugated molecule (1)
- connectivity (1)
- consequences of ethical criticism (1)
- conservation biology (1)
- conspiracy theories (1)
- contact inhibition (1)
- context (1)
- context-dependent preferences (1)
- controller failure recovery (1)
- conventional laparoscopic appendectomy (1)
- conversational agents (1)
- convex bipartite graph (1)
- coordination oligomer (1)
- coping style (1)
- copper (1)
- coppice (1)
- coprophagous beetles (1)
- copula (1)
- coral reef ecosystem (1)
- coral reef resilience (1)
- coronary arteries (1)
- correction (1)
- correlated oxides (1)
- cortical neurons (1)
- cortisol (1)
- cost-effectiveness (1)
- covalent coupling (1)
- covalent organic framework (1)
- craniofacial orthodontics (1)
- creativity (1)
- critical illness (1)
- cross-cultural comparison (1)
- cross-sectional studies (1)
- crossing-over (1)
- crown delineation (1)
- cryo-electron microscopy (1)
- cryptic peptides (1)
- cryptochrome (1)
- cryptochrome/photolyase family (1)
- crystal engineering (1)
- crystalline (1)
- cultural and media studies (1)
- culturally aware (1)
- custom-made implant (1)
- cutaneous T-cell lymphoma and Merkel cell carcinoma (1)
- cutting events (1)
- cyanoborate (1)
- cyanoborates (1)
- cyclic (alkyl)(amino)carbenes (1)
- cycling (1)
- cyclodehydrogenation (1)
- cyclodextrin (1)
- cyclophanes (1)
- cyclosporine A (1)
- cytochrome P450 3A4 (CYP3A4) (1)
- cytokine storm (1)
- cytopenia (1)
- cytoskeleton (1)
- dSTORM (1)
- dabrafenib (1)
- data filtering (1)
- deadwood (1)
- decentralized control (1)
- decision process (1)
- decision-making (1)
- decline (1)
- decomposition (1)
- deep brain stimulation (1)
- deep brain stimulation (DBS) (1)
- deep neck infection (1)
- defective ribosomal products (1)
- defoliation severity (1)
- deforestation (1)
- deformation theory (1)
- dehydrocoupling (1)
- delayed rectifier potassium channel (1)
- delivery mode (1)
- deltoid muscle (1)
- dementia with Lewy bodies (1)
- dendritic cells (1)
- dental education (1)
- dental status (1)
- dentate gyrus (1)
- dentin sealing (1)
- desiccation resistance (1)
- design (1)
- design science research (1)
- design theory (1)
- desmin (1)
- detachment force quantification (1)
- developmental biology (1)
- developmental paths (1)
- dexamethasone (1)
- diabetes mellitus (1)
- diabetic retinopathy (1)
- diagnosis in Fabry disease (1)
- diagnostic blood loss (1)
- diagnostic delay (1)
- diagnostic medicine (1)
- diaphragmatic hypomotility (1)
- diary (1)
- diborene (1)
- diet (1)
- diet breadth (1)
- differential gene expression (1)
- differential graded Lie algebra (1)
- differential nash games (1)
- differentiation (1)
- diffuse astrocytoma (1)
- diffuse large B-cell lymphoma (1)
- digital nativity (1)
- digitalisation initiative (1)
- dihydrosphingosine-1-phosphate lyase (1)
- dipole-dipole interaction (1)
- direct gaze (1)
- direct-acting antiviral (1)
- disability (1)
- disaggregation (1)
- disease severity (1)
- disembodiment (1)
- dismutations (1)
- displacement (1)
- dissolution (1)
- distal occlusion (1)
- distance compression (1)
- distance learning (1)
- distance-decay function (1)
- distance‐based specialization index (1)
- distress (1)
- disturbance extent (1)
- disturbance index (1)
- disturbance severity (1)
- diurnal (1)
- diversity (1)
- diversity gradients (1)
- diversity–disturbance relationship (1)
- donor-acceptor dyad (1)
- donor-site morbidity (1)
- donor–acceptor (1)
- donor–acceptor dyads (1)
- dopamine transporter (DAT) (1)
- dorsal clock neurons (1)
- dose escalation (1)
- drag area (1)
- drain (1)
- driving forces (1)
- drop on demand (1)
- drought impact (1)
- drug adverse reaction (1)
- drug allergy (1)
- drug discovery (1)
- drug effectiveness (1)
- drug exanthema (1)
- drug hypersensitivity (1)
- drug interaction (1)
- drug intoxication (1)
- drug monitoring (1)
- drug target (1)
- drug toxicity (1)
- drug-induced liver injury (DILI) (1)
- drug–drug interactions (DDIs) (1)
- dry spinning (1)
- dual guidance (1)
- dual-energy computed tomography (1)
- dual-room trauma suite (1)
- dung beetle (1)
- duplex structure (1)
- dyadic product BMO (1)
- dye assembly (1)
- dyes/pigments (1)
- dynamic culture (1)
- dynamic programming (1)
- dynamics (1)
- dynamics of ribosomal assembly (1)
- dynamometer (1)
- dyskinesia (1)
- dysphagia (1)
- dysplasia (1)
- dystrophin (1)
- earliest autobiographical memories (1)
- early memory (1)
- early-onset gastric cancer patients (1)
- early-onset predictors (1)
- eating and body weight disorders (1)
- eating disorders (1)
- echocardiography (1)
- ecological momentary assessment (1)
- ecosystem functioning (1)
- ectodomain cleavage (1)
- ectopic (1)
- edge detection (1)
- editorial board (1)
- effects (1)
- efficacy (1)
- efficiency (1)
- efgartigimod (1)
- egoism (1)
- ehealth (1)
- elamipretide (1)
- elbow joint (1)
- electric acoustic stimulation (EAS) (1)
- electric vehicles (1)
- electrical excitability (1)
- electroactive polymers (1)
- electrocardiography (1)
- electrochemistry (1)
- electrohydrodynamic (1)
- electrohydrodynamics (1)
- electromyographic (1)
- electromyography (1)
- electron tomography (1)
- electronic phase transitions (1)
- electronic structure (1)
- electrophilic stress (1)
- electrospinning (1)
- elevation (1)
- elevation gradient (1)
- elevational diversity patterns (1)
- embolism resistance (1)
- emergency (1)
- emergency preparedness (1)
- emotion regulation (1)
- emotions (1)
- empathy (1)
- empirical quantile mapping (1)
- encephalopathy (1)
- encryption (1)
- endemic pemphigus foliaceus (1)
- endocrine cancer (1)
- endocrine disruption (1)
- endodontics (1)
- endogenous hypercortisolism (1)
- endoglin (1)
- endoscopic (1)
- endoscopy (1)
- endothelial (1)
- endothelial cells (1)
- endotheliitis (1)
- endotoxin (1)
- endovascular therapy (1)
- endovascular treatment (1)
- enediyne (1)
- energy restriction (1)
- energy transfer (1)
- entomology (1)
- entrapment, traction (1)
- environmental factors (1)
- environmental modeling (1)
- environmental monitoring (1)
- enyne (1)
- enzyme (1)
- enzyme mechanisms (1)
- eosinophils (1)
- epicondyles (1)
- epidural anaesthesia (1)
- epigenetics (1)
- epistemic beliefs (1)
- epithelial cells (1)
- epitope prediction (1)
- epstein-barr virus (1)
- esophageal perforation (1)
- estrogens (1)
- ethics (1)
- eudaimonia (1)
- evolutionary arms race (1)
- evolutionary rescue (1)
- ex vivo (1)
- examples and counterexamples (1)
- exchange reaction (1)
- excimer (1)
- excipient (1)
- excitatory/inhibitory imbalance (1)
- exciton (1)
- exciton coupling (1)
- excitons (1)
- exercise (1)
- exosomes (1)
- expenditure paradox (1)
- experience (1)
- experiences (1)
- experiment (1)
- experimental design (1)
- experimental stroke (1)
- expert recommendation (1)
- explainable AI (1)
- explainable artificial intelligence (1)
- explainable machine learning (1)
- explanation complexity (1)
- expression (1)
- extended matching questions (1)
- extended reality (XR) (1)
- extracellular vesicles (1)
- extracorporeal hemadsorption (1)
- extracorporeal membrane oxygenation (1)
- extracorporeal membrane oxygenation (ECMO) (1)
- extracorporeal techniques in hemadsorption therapy (1)
- extracranial malignant rhabdoid tumor (1)
- eye diseases (1)
- eye gaze (1)
- eye tracking (1)
- e‐commerce (1)
- face perception (1)
- facial nerve (1)
- facilitation (1)
- fairness evaluation vs. cognitive effort (1)
- familial DCM (1)
- familial breast cancer (1)
- family caregiver (1)
- family caregivers (1)
- family relations (1)
- fascial closure (1)
- fascination with biology (1)
- fast track rehabilitation (1)
- fast-track-concepts (1)
- fatigue (1)
- faulting (1)
- fear conditioning (1)
- fear expression (1)
- fear stimuli (1)
- fears (1)
- feasibility study (1)
- feeding (1)
- female Fabry patients (1)
- female aggression (1)
- femur (1)
- fenestration (1)
- ferroptosis (1)
- fiber (1)
- fibroblast activation protein (1)
- fibromyalgia (1)
- filamin-C (1)
- financial linkages (1)
- fire (1)
- fish bone (1)
- fish oil (1)
- fistulizing Crohn’s Disease (1)
- flare phenomenon (1)
- flat silicone bolus (1)
- flexible CO2 laser (1)
- flight control (1)
- flood (1)
- floral larceny (1)
- flotillin-1 lipid rafts (1)
- flow path (1)
- flower morphology (1)
- flower visitors (1)
- flowering grassland plants (1)
- fluctuation (1)
- fluorescence correlation spectroscopy (1)
- fluorescence in situ hybridisation (1)
- fluorescence in situ hybridization (FISH) (1)
- fluorescence resonance energy transfer (FRET) (1)
- fluorescence-aided identification technique (1)
- fluorescent probes (1)
- fluoroquinolones (1)
- fluoxetine (1)
- fly pollination (1)
- flybow (1)
- focal radiotherapy (1)
- focused surgical approach (1)
- folding (1)
- foliation (1)
- food contact materials (1)
- food quality (1)
- food supplement (1)
- foot (1)
- forage resources (1)
- foragers (1)
- force feedback (1)
- forearm (1)
- forecast (1)
- foreign body ingestion (1)
- forensic neuropathology (1)
- forensic neurotraumatology (1)
- forest communities (1)
- forest conversion (1)
- forest degradation (1)
- forest ecology (1)
- forest fragmentaion (1)
- forest proximity (1)
- forgotten joint score (1)
- formation control (1)
- fpVCT (1)
- fractionated spacecraft (1)
- fracture sequelae (1)
- fracture sequelae shoulder (1)
- fragility fracture (1)
- fragment screening (1)
- fragmentation (1)
- framing (1)
- free skin grafts (1)
- freezing of gait (1)
- freezing of gait (FOG) (1)
- fruit (1)
- fruit temperature (1)
- fully convolutional neural networks (1)
- functional initiators (1)
- functional magnetic resonance imaging (1)
- functional renormalization group (1)
- fungal sinusitis (1)
- fungi (1)
- funnel mesh (IPST) (1)
- furan (1)
- fusion (1)
- future prediction (1)
- fuzzy classification (1)
- gait analysis (1)
- gait initiation (1)
- gait modulation (1)
- galectin-2 (1)
- gallotannins (1)
- gambling (1)
- gamification (1)
- gamma diversity (1)
- gastric bypass (1)
- gastric cancer in young patients (1)
- gastric emptying (1)
- gastroenterology (1)
- gastrointestinal perforation (1)
- gaze stability (1)
- gefitinib (1)
- gene (1)
- gene regulation (1)
- gene variant (1)
- general practice (1)
- genetic algorithm (1)
- genetic association (1)
- genetic screen (1)
- genetic susceptibility (1)
- genetic testing (1)
- genome-wide screen (1)
- genotype-phenotype correlation (1)
- genotype/phenotype correlation (1)
- geoarchaeology (1)
- geoelectrical monitoring (1)
- geometry (1)
- geomorphological mapping (1)
- geomorphology (1)
- geophysical prospection (1)
- geovisualization (1)
- gephyrin (1)
- geriatric (1)
- german clinical cancer registry group (1)
- germline mutation (1)
- gingival (1)
- glaucoma (1)
- glaucoma progression (1)
- glecaprevir/pibrentasvir (1)
- glenoid (1)
- glenoid bonegrafting (1)
- glial damage (1)
- glial fibrillary acidic protein (1)
- glioblastoma multiforme (1)
- glioma (1)
- gliomedin (1)
- global warming (1)
- globotriaosylceramide (1)
- globus pallidus pars interna (GPi) (1)
- glucocorticoid receptor (1)
- glucose restriction (1)
- glycogen synthase kinase-3 β (GSK-3β) (1)
- glycolysis (1)
- glycolytic flux control (1)
- glycopeptide antibiotics (1)
- glycoprotein receptor Ibα (1)
- gold (1)
- gradient boosting machine (1)
- grading system of chondral defects (1)
- graft versus host disease (1)
- granulocytes (1)
- granulophagy (1)
- granulostasis (1)
- graph algorithm (1)
- gray level co-occurrence matrix (1)
- grazing (1)
- green energy (1)
- group 8 metals (1)
- growth rate (1)
- guanine nucleotide exchange factor (GEF) (1)
- guard cell (1)
- guideline adherence (1)
- guideline usage (1)
- guild constancy (1)
- gypsy moth (1)
- hERG (1)
- habitat change (1)
- habitat types (1)
- haemostasis (1)
- halophyte (1)
- hand movements (1)
- hand pollination (1)
- handball (1)
- harmonic measure (1)
- harvests (1)
- hawkmoth (1)
- head depression fractures (1)
- health care workers (1)
- health effects (1)
- health literacy (1)
- health tracker (1)
- health-related fitness (1)
- health-related quality of life (1)
- healthcare costs (1)
- healthcare professionals (1)
- healthcare workers (1)
- hearing aid (1)
- hearing impairment (1)
- hearing loss (1)
- hearing preservation (1)
- heart failure training group (1)
- heavy rainfall (1)
- hedonia (1)
- helicase (1)
- helicene (1)
- hematopoiesis (1)
- hematopoietic stem cells (1)
- hematotoxicity (1)
- heme oxygenase-1 (1)
- hemibrain (1)
- hemolysin (1)
- hepatitis C virus (1)
- hepatocellular carcinoma (1)
- hepatotoxicity (1)
- herbivores (1)
- hereditary alpha-tryptasemia (1)
- hernia (1)
- heterochromatin (1)
- heterogeneity (1)
- heteroskedasticity (1)
- hiPSC-CM (1)
- hidden action (1)
- hidradenitis suppurativa (1)
- hierarchical drift-diffusion modeling (1)
- hierarchical modeling (1)
- high dose dexamethasone suppression test (1)
- high intelligence (1)
- high tibial valgus osteotomy (1)
- high-accuracy 3D measurements (1)
- high-dose-rate brachytherapy boost (1)
- high-flow nasal cannula (1)
- high-intensity interval training (1)
- high-pressure freezing (1)
- high-sensitivity FEES (1)
- higher education (1)
- highly porous materials (1)
- hill numbers (1)
- hippocampal mossy fiber bouton (1)
- histones (1)
- historical document analysis (1)
- holotomography (1)
- homogeneous catalysis (1)
- homology modeling (1)
- homotypic fusion and protein sorting (1)
- honeybee (1)
- honeybees (1)
- hospitalization (1)
- host discrimination (1)
- host response (1)
- host selection (1)
- hotspot analysis (1)
- house dust mite allergy (1)
- human (1)
- human brain endothelium (1)
- human breast (1)
- human disturbance (1)
- human induced pluripotent stem cells (hiPSCs) (1)
- human pressure (1)
- human-centered AI (1)
- human-robot interaction (1)
- humanized mice (1)
- humanoid (1)
- humans (1)
- hyaluronan-related enzymes (1)
- hydraulic architecture (1)
- hydraulic conductivity (1)
- hydraulic efficiency (1)
- hydraulic variability (1)
- hydrazone (1)
- hydroboration (1)
- hydrogen storage (1)
- hydrological drought (1)
- hydroxy-dabrafenib (1)
- hymenoptera (1)
- hyper-IgM syndrome type 2 (HIGM2) (1)
- hyperbolic area (1)
- hypertension (1)
- hypophosphatasia (1)
- hypoxia (1)
- i.v. thrombolysis (1)
- iTotal (1)
- iatrogenic anemia (1)
- identification (1)
- identity defense (1)
- ideomotor theory (1)
- ileocecal resection (1)
- illusion of self-motion (1)
- image analysis (1)
- image processing (1)
- imaging (1)
- imaging changes (1)
- imaging techniques (1)
- imidazolate (1)
- immune control (1)
- immune impairment (1)
- immune therapy (1)
- immune-informatics (1)
- immune-related adverse events (1)
- immunity (1)
- immunization (1)
- immunocytochemistry (1)
- immunodrug delivery (1)
- immunology (1)
- immunomodulation (1)
- immunonutrition (1)
- immunophenotyping (1)
- immunosorbents (1)
- immunotherapy-induced hypophysitis (1)
- impedance spectroscopy (1)
- implant design (1)
- implant survival (1)
- implantation (1)
- implementation (1)
- implicit association test (1)
- impulsive systems (1)
- in vitro model (1)
- in vitro-in vivo correlation (1)
- in vivo (1)
- in vivo experiments (1)
- in-bed cycling (1)
- incentives (1)
- incidental lifestyle physical activity (1)
- incisors (1)
- inclusion of nature in one’s self (1)
- indicator species (1)
- indigenous (1)
- individual case review (1)
- individual mobility (1)
- individual silicone bolus (1)
- individualized surgery (1)
- indoor dust (1)
- induced matching (1)
- induced pluripotent stem cell cardiomyocytes (1)
- inducible cyclooxygenase-2 (COX-2) (1)
- induction (1)
- infarction (1)
- infarction size (1)
- infection prevention (1)
- inferior vena cava (1)
- infinite-dimensional systems (1)
- inflammation marker (1)
- inflammatory bowel disease (1)
- inflammatory cascades (1)
- inflated fruiting calyx (1)
- infliximab (1)
- informal care (1)
- informal caregiving (1)
- information storage and retrieval (1)
- information systems and information technology (1)
- inherited peripheral neuropathy (1)
- inhibition (1)
- inhibitory postsynapse (1)
- inner ear (1)
- innervation (1)
- inorganic chemistry (1)
- inpatient rehabilitation (1)
- input-to-state stability (1)
- insect (1)
- insect brain (1)
- insect communities (1)
- insect decline (1)
- insect disturbance (1)
- insect-fungus symbiosis (1)
- insecticidal knockdown (1)
- insects (1)
- insertion (1)
- instrument (1)
- insular cortex (1)
- insulin signaling (1)
- integrated stress response (1)
- integrators (1)
- integrin α5β1 (1)
- integrin αvβ3 (1)
- intelligent system (1)
- intelligent systems (1)
- intelligent virtual agents (1)
- intensive care unit (1)
- intentional action (1)
- intentional directions (1)
- interaction networks (1)
- interactive vegetation (1)
- interaural level difference (1)
- interaural time difference (1)
- interdisciplinary moral philosophy (1)
- interelectrode-distance (1)
- interferon beta-1a (1)
- interior and exterior acts (1)
- intermediate disturbance hypothesis (1)
- intermediate host (1)
- internalized stigmatization (1)
- internet of things (1)
- internet traffic (1)
- interstage aspiration (1)
- interventional procedures (1)
- interventional radiology (1)
- inter‐tegular distance (1)
- intestinal control (1)
- intra-annual time-series (1)
- intraabdominal abscess (1)
- intracerebral haemorrhage (1)
- intracranial hemorrhage (1)
- intraepidermal nerve fiber density (1)
- intragastric balloon (1)
- intravenous immunoglobulin (1)
- intraventricular therapy (1)
- intrinsic metabolism (1)
- introgressive hybridization (1)
- invasion (1)
- invasive electric stimulation (1)
- invasive fungal infection (1)
- invasive pulmonary aspergillosis (1)
- inversion (1)
- ion channel (1)
- ion channels (1)
- ionic liquids (1)
- ipilimumab (1)
- irradiation (1)
- ischemia/reperfusion injury (1)
- ischemic penumbra (1)
- isocenter (1)
- isolation (1)
- isosteviol sodium (STVNA) (1)
- isotopes (1)
- isotopic labelling (1)
- isturisa (1)
- jaw bone (1)
- jaw clenching (1)
- jugular paraganglioma (1)
- juvenile hormone (1)
- juvenile progressive respiratory insufficiency (1)
- keratin-18 (1)
- key event relationship (1)
- kidney function (1)
- kinematics (1)
- kinetics (1)
- kinetin (1)
- kisspeptin/galanin/spexin signalling (1)
- knee joint (1)
- knee replacement (1)
- knockout (1)
- labor demand (1)
- labor market (1)
- lactic acidosis (1)
- laminopathy (1)
- land surface temperature (LST) (1)
- land use change (1)
- land use/cover pattern (LUCP) (1)
- landmark (1)
- landmark panorama (1)
- landscape diversity (1)
- language contact (1)
- language-image pre-training (1)
- large artery vasculitis (1)
- large loop excision of the transformation zone (LLETZ) (1)
- larval and pupal development (1)
- laser spectroscopy (1)
- laser surgery (1)
- late response (1)
- late-onset (1)
- latency type (1)
- latent growth curve model (1)
- lateral trochlear undercoverage (1)
- lava (1)
- lead (1)
- leaf (1)
- learning (1)
- learning and memory (1)
- learning arbitrary mappings (1)
- learning curve (1)
- left hemicolectomy (1)
- left ventricular ejection fraction (1)
- left ventricular performance (1)
- left-ventricular assist device (1)
- legislation (1)
- lepidoptera (1)
- leptomeningeal cells (1)
- lessons learned (1)
- lewis acid/base adducts (1)
- lewis superacid (1)
- lexical innovation (1)
- life events (1)
- life story (1)
- life-history traits (1)
- light-gated proteins (1)
- light‐gated (1)
- line notations (1)
- lineage differentiation (1)
- linear scaling (1)
- linker influence (1)
- lipid droplets (1)
- lipids (1)
- liposome (1)
- liquid chromatography/mass spectrometry (1)
- liraglutide (1)
- literature review (1)
- liver fibrosis (1)
- lncRNA (1)
- local cues (1)
- localization microscopy (1)
- locked shoulder dislocation (1)
- locomotion (1)
- locust outbreak (1)
- loess plateau (1)
- logistics (1)
- loneliness (1)
- long QT syndrome (1)
- long non-coding RNA (1)
- long-chain base (1)
- long-read sequencing (1)
- longitudinal decrease (1)
- longitudinal studies (1)
- loss (1)
- low back pain (1)
- low carb (1)
- low-grade mucinous neoplasm (1)
- low-risk intra-abdominal infections (1)
- lower extremity (1)
- lower grade glioma (1)
- luciferase (1)
- lyapunov methods (1)
- lymph node dissection (1)
- lymph nodes (1)
- lymphadenectomy (1)
- lymphocytes (1)
- lymphoma (1)
- lymphotoxicity (1)
- lysosomal disruption (1)
- lysosomal dysfunction (1)
- lysosomal enzyme (1)
- lysosomal storage disease (1)
- m exercise training (1)
- mRNA (1)
- mTORC1 (1)
- macrocycle (1)
- macrocycles (1)
- macrophage (1)
- macroscopic recurrence (1)
- macular neovascularization (1)
- magnetic compass (1)
- magnetic properties and materials (1)
- magnetoactive materials (1)
- main group element halides (1)
- major bleeding (1)
- major depression (1)
- major environmental values (1)
- major histocompatibility complex (1)
- male breast cancer (1)
- malnutrition (1)
- mammalian male germline (1)
- mammalian system (1)
- mannan (1)
- mapping (1)
- marginal gap formation (1)
- marine macroalgae (1)
- maser (1)
- mass casualties (1)
- mastocytosis (1)
- matched pair (1)
- maternal (1)
- maternal critical care (1)
- mathematical modelling (1)
- matrix metallopeptidase-1 (1)
- matrix metalloproteinase (1)
- maximum likelihood difference scaling (1)
- meadow (1)
- mean annual temperature (1)
- meaning (1)
- meaning-making (1)
- measels virus (1)
- measles virus (1)
- mechanical property (1)
- mechanical ventilator weaning (1)
- mechanisms (1)
- media equation (1)
- medial pivot (1)
- mediastinitis (1)
- medical data integration center (1)
- medical education (1)
- medical informatics initiative (1)
- medical nutrition therapy (1)
- medical students (1)
- medical therapy (1)
- medical-grade poly(ε-caprolactone) (1)
- medication-related osteonecrosis of the jaw (1)
- medicine (1)
- medieval manuscripts (1)
- medium-sized animals (1)
- medullary thyroid cancer (1)
- medulloblastoma (1)
- melanocytic markers (1)
- melanoma metastases (1)
- melt electrowriting (MEW) (1)
- membrane potential (1)
- memory B cells (1)
- meningeal blood-csf barrier (1)
- menues (1)
- merocyanine (1)
- merocyanines (1)
- mesenchymal stem cells (1)
- mesenchymal stromal cells (1)
- mesenteric stenting (1)
- meta-view (1)
- metabolic flux analysis (1)
- metabolic network model (1)
- metabolism and growth (1)
- metabotropic glutamate (mGlu) receptor (1)
- metacognitive competences (1)
- metagenomics (1)
- metal matrix (1)
- metal-free (1)
- metalloproteinase (1)
- metals (1)
- metamorphic buffer layer (1)
- metapopulation (1)
- metastasis-directed therapy (1)
- meteorological drought (1)
- methionine (1)
- methionine restriction (1)
- methyl viologen (1)
- methylation (1)
- methylphenidate (1)
- metyrapone (1)
- miR-182-5p (1)
- micro-computed tomography (1)
- micro-traumatic (1)
- microSPLiT (1)
- microbiological culture (1)
- microbiology (1)
- microbiomes (1)
- microbiota (1)
- microparticles (1)
- microphysiological systems (MPS) (1)
- microtubules (1)
- microvascular complications (1)
- microvascular endothelial cells (1)
- microvasculature (1)
- mid-infrared sensing (1)
- midbrain (1)
- midfrontal theta (1)
- migraine (1)
- migrants (1)
- migration (1)
- mild cognitive impairment (1)
- mindfulness (1)
- mineral trioxide aggregate (1)
- minimally invasive surgery (1)
- mitochondria function and morphology (1)
- mitochondrial DNA polymerase γ (1)
- mitochondrial FAO (1)
- mitotane (1)
- mixed infection (1)
- mixed-cultural (1)
- mobile health (1)
- mobile streaming (1)
- model (1)
- moderate-penetrance genes (1)
- modified Sugarbaker technique (1)
- moisture balance (1)
- molecular (1)
- molecular alterations (1)
- molecular docking (1)
- molecular graphs (1)
- molecular imaging (1)
- molecular mobility (1)
- molecular modeling (1)
- molecular orbitals (1)
- molecular representation (1)
- molecule isomorphism (1)
- monocyte (1)
- moral hazard (1)
- moral reasoning (1)
- moral responsibility (1)
- morphology (1)
- motion compensation (1)
- motion tracking (1)
- motivation (1)
- motor (1)
- motor control (1)
- motor neuron degeneration (1)
- motor neuropathy (1)
- mountain ecology (1)
- mountain ecosystems (1)
- mountain pines (1)
- mountains (1)
- mouse (1)
- movable sliding gantry (1)
- movement disorders (1)
- moving rubber hand illusion (1)
- mucin (1)
- mucosal healing (MH) (1)
- multi-organ chip (1)
- multi-tyrosine kinase inhibitor (1)
- multicenter (1)
- multichromophores (1)
- multicomponent stretching (1)
- multilayered skin (1)
- multimodal data (1)
- multimodal pain management (1)
- multiple brain metastases (1)
- multiple choice questions (1)
- multiple linear regression (1)
- multiscalar holotomography (1)
- multispectral data (1)
- multivariate Gaussian distribution (1)
- multivariate data analysis (1)
- multivariate quantile delta mapping (1)
- multivariate statistical process control (SPC) (1)
- multi‑center cohort study (1)
- muscle disease (1)
- muscle injury (1)
- muscle strength (1)
- mutational targeting (1)
- mycobacterial infection (1)
- mycophenolate (1)
- mycotoxin (1)
- myelination (1)
- myocardial work (1)
- nanoarchitecture (1)
- nanocellulose (1)
- nanogels (1)
- nanomedicine (1)
- nanopore (1)
- naphthalene diimide (1)
- narrow band imaging (NBI) (1)
- natural killer cells (1)
- natural pest control (1)
- natural product hybrids (1)
- natural products (1)
- naturalistic stimuli (1)
- nature conservation (1)
- nausea and emesis (1)
- near infrared emitter (1)
- near infrared spectroscopy (1)
- necroptosis (1)
- nectar macronutrients (1)
- need satisfaction (1)
- negative affect (1)
- neglected groups (1)
- neisseria meningitidis (1)
- neoadjuvant (1)
- neoadjuvant therapy (1)
- neophyte trees (1)
- nerve agent (1)
- nerve compression (1)
- nervous system (1)
- nest site selection (1)
- nesting (1)
- network analysis (1)
- networked predictive control (1)
- neume notation (1)
- neural coding (1)
- neural network architecture (1)
- neuraminidase (1)
- neuro-/photoreceptor degeneration (1)
- neuroblastoma – diagnosis (1)
- neuroendocrine tumor (1)
- neurology (1)
- neurolysis (1)
- neuromelanin granules (1)
- neuromuscular junction (1)
- neuron (1)
- neuronal network (1)
- neurons (1)
- neuropeptide signalling (1)
- neuropeptides (1)
- neuroplasticity (1)
- neuroprotection (1)
- neuropsychiatric disorders (1)
- neurotrophic factor (1)
- neurotrophins (1)
- neurovasculature (1)
- next generation sequencing (1)
- next generation sequencing (NGS) (1)
- next-generation sequencing (1)
- niche (1)
- nitrate (1)
- nitric oxide (1)
- nitrite (1)
- nitrogen uptake (1)
- nivolumab (1)
- non-Lipschitz optimization (1)
- non-canonical translation (1)
- non-interventional (1)
- non-invasive ventilation (1)
- non-native accent (1)
- non-survivors (1)
- non-visual (1)
- nonhuman primates (1)
- nonlinear inverse problems (1)
- nonlinear systems (1)
- nonsmooth optimization (1)
- nonverbal communication (1)
- noradrenaline (1)
- noradrenaline transporter (1)
- norepinephrine transporter (1)
- northern Tanzania (1)
- nosocomial transmission (1)
- nuclear factor ‘kappa-light-chain-enhancer’ of activated B-cells (NFκB) (1)
- nucleic acid motifs (1)
- nucleolus (1)
- nucleosomes (1)
- nucleotide excision repair (1)
- nucleus (1)
- numerical cognition (1)
- numerical finance (1)
- nurse bees (1)
- nurses (1)
- nutritional counseling (1)
- nutritional medical needs (1)
- nutritional risk screening (1)
- nycthemeral intraocular pressure (1)
- object detection (1)
- object-based image analysis (1)
- observation (1)
- observational (1)
- obstacle avoidance (1)
- obstetrics (1)
- occupation (1)
- octogenerians (1)
- octopamine receptors (1)
- offspring (1)
- oil spill (1)
- oilseed rape (1)
- older employees (1)
- oligodendrocyte (1)
- oligodendrocytes (1)
- oligodendroglioma (1)
- oligorecurrence (1)
- oligothiophene (1)
- oligothiophenes (1)
- olive (1)
- omega-3 fatty acid (1)
- omega-6 fatty acid (1)
- omics (1)
- oncodermatology (1)
- oncology outpatients (1)
- oogenesis (1)
- open abdomen (1)
- open spaces (1)
- openEHR (1)
- operating platform (1)
- operation (1)
- operative planning (1)
- optic flow (1)
- optical (1)
- optical diversity (1)
- optical materials (1)
- optical underwater 3D sensor (1)
- oral (1)
- oral health (1)
- oral microbiome (1)
- oral nutrition supplements (1)
- oral-health-related quality of life (1)
- ordinary differential equations (1)
- organic light emitting diodes (1)
- organic photodiodes (1)
- organic solar cells (1)
- organic synthesis (1)
- organocatalytic (1)
- organoid (1)
- organotypic hippocampal slice cultures (OHSC) (1)
- orientation (1)
- origin (1)
- oro-antral communication (1)
- oro-antral fistula (1)
- oroantral fistula (1)
- orofacial granulomatosis (1)
- orthopoxvirus (1)
- oscillating biomagnetic fields (1)
- osilodrostat (1)
- osmotic stress (1)
- osteogenic differentiation (1)
- osteogenic potential (1)
- osteoporosis (1)
- osteosynthesis (1)
- outbreak (1)
- outcome prediction (1)
- outer hair cell (OHC) (1)
- outreach (1)
- over-determined problem (1)
- overall survival (1)
- overfishing (1)
- overwork (1)
- oxime (1)
- oxytosis/ferroptosis (1)
- p.R245H (1)
- p.S298P (1)
- p53 (1)
- p97/VCP (1)
- pain-associated behavior (1)
- paired (1)
- paleoecology (1)
- paleogeography (1)
- palladium (1)
- palliative care (1)
- palynology (1)
- pancreatic adenocarcinoma (PDAC) (1)
- pancreatic neoplasms (1)
- pancreatic surgery (1)
- pangolin (1)
- panorama (1)
- par-seqFISH (1)
- parastomal hernia (1)
- parathyroid adenoma (1)
- parathyroid hormone 1 receptor (1)
- parenteral nutrition (1)
- parents (1)
- parthenogenesis (1)
- partial correlation (1)
- partial deafness treatment (1)
- partial least square regression (1)
- participation (1)
- participation in clinical trials (1)
- particulate matter (1)
- passage of time (1)
- pasture (1)
- patellofemoral relationship (1)
- paternal (1)
- paternal age effect (1)
- path analysis (1)
- path integration (1)
- pathogenesis (1)
- pathogenic TP53 germline variant (1)
- pathway analysis (1)
- patient (1)
- patient access (1)
- patient blood management (1)
- patient reported outcome measures (1)
- patient safety (1)
- patient serum (1)
- patient-reported outcomes (1)
- patient-specific (1)
- patient–physician relationship (1)
- pectoralis major transfer (1)
- pedagogical content knowledge (1)
- pediatric adrenocortical cancer (1)
- pediatric adrenocortical carcinoma (1)
- pediatric adrenocortical tumor (1)
- pediatrics (1)
- pedunculopontine nucleus (PPN) (1)
- pegylated insulin-like growth factor 1 (1)
- pembrolizumab (1)
- pemphigus foliaceus (1)
- pemphigus vulgaris (1)
- penetrating ileitis (1)
- penicillin allergy (1)
- penicillin hypersensitivity (1)
- pension reform (1)
- pentacene (1)
- peptide backbone (1)
- peptide fragment (1)
- peptide receptor radionuclide therapy (1)
- peptide tyrosine tyrosine (PYY) (1)
- peptide tyrosine tyrosine 3-36 (PYY\(_{3-36}\)) (1)
- peptides (1)
- percussion core probing (1)
- performance (1)
- performance monitoring (1)
- perfusion culture (1)
- perianal fistulas (1)
- perinatal (1)
- periodontal disease (1)
- periodontal therapy (1)
- perioperative antibiotic prophylaxis (1)
- perioperative therapy (1)
- peripartum (1)
- peripheral nerve (1)
- peripheral nerve involvement (1)
- periphery-brain interactions (1)
- periprosthetic infection (1)
- periprosthetic joint infection (1)
- peritoneal metastasis (1)
- peritonitis (1)
- periurban (1)
- permafrost (1)
- peroxisome (1)
- personalised medicine (1)
- personalised orthopaedic implantation (1)
- personality traits (1)
- personalized medicine (1)
- perturbation (1)
- perylene dyes (1)
- perylenebisimide (1)
- petal (1)
- phage (1)
- phagocytes (1)
- phalloidin stain (1)
- pharmacotherapy (1)
- pharmacovigilance (1)
- phase I (1)
- phase II (1)
- phenomenology of acting and willing (1)
- phenotypic plasticity (1)
- phenprocoumon (1)
- pheochromocytoma/paraganglioma (1)
- pheromone trail (1)
- philanthidae (1)
- phlorizin (1)
- phosphatidyl-inositol-3-kinase p110 alpha (1)
- phosphatidylinositol (1)
- phosphatidylserine (1)
- phosphoantigen (1)
- phosphodiesterase (1)
- phosphodiesterase-4 (1)
- phosphodiesterase-inhibitors (1)
- phosphoglycolate phosphatase (1)
- phospholipase C gamma 2 (1)
- phosphorylated tau protein (1)
- phosphorylation (1)
- photo-crosslinking (1)
- photodynamic therapy (1)
- photoluminescence (1)
- photolyase (1)
- photon counting (1)
- photon‐correlation (1)
- photoplethysmography (1)
- photopolymerization (1)
- photoreflectance (1)
- photosensor (1)
- photothrombosis (1)
- phototropin (1)
- physical education (1)
- physical examination (1)
- physicochemical characterization (1)
- physiologically based pharmacokinetic (PBPK) modeling (1)
- physiology (1)
- phytohormones (1)
- pituitary (1)
- pityriasis rubra pilaris (1)
- placement (1)
- plan sciences (1)
- plant cuticle (1)
- plant guilds (1)
- plant richness (1)
- plant sphingolipid metabolism (1)
- plant system (1)
- plant–insect interactions (1)
- plant–pollinator interactions (1)
- plasma NMR (1)
- plasticity (1)
- plasticizers (1)
- platelet activation (1)
- platelet inhibition (1)
- platelet physiology (1)
- platelet receptors (1)
- platelet responsiveness (1)
- platelet-rich fibrin (1)
- platform economy (1)
- platinum (1)
- platinum complexes (1)
- plausibility (1)
- podocytes (1)
- point cloud (1)
- pointing gestures (1)
- pointing motives (1)
- polar ion transport (1)
- pollen (1)
- pollen nutrients (1)
- pollination (1)
- pollination network (1)
- pollination services (1)
- pollinator (1)
- pollinator decline (1)
- pollinator diversity (1)
- pollution (1)
- poly(ADP-ribose) polymerase inhibitors (1)
- poly(lactide-co-glycolide) (1)
- polycaprolactone (1)
- polycarbonates (1)
- polycationic peptides (1)
- polyethylene glycol (1)
- polygenic risk score (1)
- polymer electrolytes (1)
- polymers (1)
- polymethylmethacrylate (1)
- polymorphisms (1)
- polynomial chaos (1)
- polyp (1)
- polypeptoids (1)
- pontryagin maximum principle (1)
- population inversion (1)
- population pharmacokinetics (1)
- population-based studies (1)
- portable (1)
- posaconazole (1)
- positive affect (1)
- positive selection (1)
- post-error slowing (1)
- post-translational modifications (1)
- postcardiotomy shock (1)
- posterior cruciate ligament (1)
- posterior tibial slope (1)
- postmortem (1)
- postnatal depression (1)
- postoperative inflammation (1)
- postoperative rehabilitation (1)
- postpolymerization modification (1)
- postural control (1)
- posturomed (1)
- post‐truth (1)
- potentiation (1)
- poxvirus (1)
- practical reasoning (1)
- pre-error speeding (1)
- pre-service teacher (1)
- preanalytical conditions (1)
- precipitation (1)
- precision horticulture (1)
- precision oncology (1)
- precision-cut lung slices (1)
- preclinical research (1)
- predation stress (1)
- predictive modeling (1)
- prefabricated granules (1)
- prehabilitation (1)
- preoperative planning (1)
- presence (1)
- prestyloid recess (1)
- presynaptic (1)
- presynaptic ER dynamics (1)
- presynaptic homeostasis (1)
- presynaptic inhibition (1)
- prevention (1)
- primary aldosteronism (1)
- primary aromatic amine (1)
- primary care (1)
- primary cutaneous follicular B-cell lymphoma (1)
- primary hyperparathyroidism (1)
- primary hypophysitis (1)
- pristine forests (1)
- pro-inflammatory cytokines (1)
- probabilistic reversal learning (1)
- professional competence (1)
- professional image enhancement technique (PIET) (1)
- progeria (1)
- prognostic awareness (1)
- prognostic marker (1)
- prognostic markers (1)
- programmed cell death receptor-1 (1)
- proliferation (1)
- prompt engineering (1)
- propensity score matching (1)
- prosociality (1)
- prospective (1)
- prostate adenocarcinoma (1)
- prostate-specific antigen (1)
- prostate-specific membrane antigen (1)
- prosthetic dentistry/prosthodontics (1)
- prosthetic design (1)
- protected areas (1)
- protection status (1)
- protein (1)
- protein alkylation (1)
- protein chip (1)
- protein corona (1)
- protein kinase (1)
- protein kinase pathway (1)
- protein phosphorylation (1)
- protein sensing (1)
- protein variant (1)
- proteomic (1)
- proton beam therapy (1)
- prototheca (1)
- proximal gradient method (1)
- proximal humeral fracture (1)
- proximity labeling (1)
- proximity ligation (1)
- psychiatric disorders (1)
- psycho-oncology (1)
- psychological capital (1)
- psychophysics (1)
- psychosocial (1)
- psychotropic medications (1)
- pubic symphysis (1)
- public health (1)
- public health preparedness (1)
- public speaking (1)
- pull effect (1)
- pulmonary artery pressure (1)
- punctate mechanical allodynia (1)
- purine derivatives (1)
- push–pull thienylthiazole (1)
- python (1)
- qualitative approaches (1)
- quantitative MRI (1)
- quantity discrimination (1)
- quantum dot (1)
- quartz-pebble conglomerate (1)
- questionnaire development (1)
- quinoa (1)
- quinolones (1)
- quinone (1)
- radar data (1)
- radial forearm flap (1)
- radical (1)
- radical cystectomy (1)
- radical reactions (1)
- radiochemistry (1)
- radiography (1)
- radiology (1)
- radiopharmaceuticals (1)
- radiotracer (1)
- radiotracer kinetics (1)
- random forest classification (1)
- random forest modeling (1)
- randomized controlled trial (1)
- range limits (1)
- rare diseases (1)
- rat study (1)
- rationalization (1)
- rats (1)
- re-induction (1)
- re-irradiation (1)
- real laboratory (1)
- real world data (1)
- real world evidence (1)
- real-world application (1)
- real-world data (1)
- rearranged during transfection (1)
- reasoning biases (1)
- recapitulation (1)
- receptors (1)
- recommender agent (1)
- reconstruction (1)
- recurrence (1)
- recurrent (1)
- red blood cell transfusion (1)
- red blood cells (1)
- regeneration (1)
- regenerative capacity (1)
- regenerative potential (1)
- region of interest (1)
- regional cerebral oxygenation saturation (1)
- regional climate model (RCM) (1)
- regional transient osteoporosis (1)
- registry (1)
- regulatory T-cell (Treg) (1)
- rehabilitation (1)
- reinforcement learning (1)
- reintroduction (1)
- relapse (1)
- religion (1)
- religiosity (1)
- remote care/telehealth (1)
- remote monitoring (1)
- renal function (1)
- renal inflammation (1)
- reoxygenation (1)
- repair (1)
- replication stress (1)
- reporting and data system (1)
- reproducibility (1)
- reproductive toxicity (1)
- research (1)
- resident memory T cells (1)
- resource selection (1)
- respiratory chain (1)
- respiratory failure (1)
- response durability (1)
- response modalities (1)
- response surface (1)
- response-time analysis (1)
- responsivity (1)
- restaurants (1)
- restrictive cardiomyopathy (1)
- retention strategies (1)
- retina (1)
- retinal angiomatous proliferation (1)
- retinitis pigmentosa (1)
- retranslational research (1)
- revision arthroplasty (1)
- reward positivity/FRN/MFN/N2 (1)
- rhabdoid differentiation (1)
- rhabdoid melanoma (1)
- rheumatoid arthritis (1)
- rhodamine–phalloidin stain (1)
- rhodopsin phosphodiesterase (RhoPDE) (1)
- ribosome (1)
- ribosome biogenesis (1)
- rich vehicle routing problem (1)
- right-left comparison (1)
- ring opening reactions (1)
- ring-opening polymerization (1)
- risk assessment (1)
- risk factor (1)
- risk prediction scores (1)
- risk score (1)
- risks (1)
- risperidone (1)
- rituximab (1)
- road traffic (1)
- robot (1)
- robot-supported training (1)
- robotic surgery (1)
- robotic tutor (1)
- robustness (1)
- role of mathematics in STEM (1)
- room-temperature phosphorescence (RTP) (1)
- root-canal treatment (1)
- rove beetle (1)
- rt-PA (1)
- rule retrieval (1)
- ruxolitinib (1)
- sRNA biogenesis (1)
- sSupramolecular interaction (1)
- saccotomy (1)
- sacrifice (1)
- safety (1)
- safety behavior (1)
- safety-efficiency trade-off (1)
- salicylic acid (1)
- salience theory (1)
- saliency maps (1)
- salt tolerance (1)
- salvage (1)
- saproxylic beetles (1)
- sarcoglycanopathy (1)
- sarcoma (1)
- satellite data (1)
- satellitosis (1)
- satisfaction with life (1)
- scaffold (1)
- scapula (1)
- scapula alata (1)
- scapular winging (1)
- scheduling (1)
- school (1)
- school statistics (1)
- school-based prevention (1)
- schoolchildren (1)
- science, technology and society (1)
- scoliosis (1)
- scoping review (1)
- screening (1)
- seasonal (1)
- seasonality (1)
- secondary education (1)
- secondary reconstruction (1)
- secondary wound dressing (1)
- sectoral planning (1)
- secure group communication (1)
- sedimentology (1)
- segmental centers of mass (1)
- selective mutism (1)
- selenolysis (1)
- self-deception (1)
- self-efficacy (1)
- self-help (1)
- self-infliction (1)
- self-injury (1)
- self-organization (1)
- semantic change (1)
- semantic interoperability (1)
- semantic segmentation (1)
- semigroup of holomorphic functions (1)
- senescence‐associated secretory phenotype (1)
- sensitivity and specificity (1)
- sepsis (1)
- septic (1)
- septic shock (1)
- sequential quadratic hamiltonian method (1)
- serotonin (1)
- serotonin transporter (1)
- serratus anterior (1)
- serum concentration (1)
- serum retention (1)
- settlement growth (1)
- sex (1)
- sex chromosomes (1)
- sex differences (1)
- sex hormone (1)
- sex linked pigmentation pattern (1)
- sex pheromones (1)
- sex-determining genes. (1)
- sexual and spiritual abuse (1)
- sexual antagonistic genes (1)
- sexual development dysgenesis (1)
- sexual dimorphism (1)
- shade cover (1)
- shape (1)
- shear wave elastography (1)
- shedding (1)
- shock (systemic, cardiac or circulatory) (1)
- short-chain fatty acids (1)
- short‑term refrigeration (1)
- shoulder (1)
- shoulder arthroplasty (1)
- shoulder injuries (1)
- side-effects (1)
- signal to noise ratio (1)
- signal voids (1)
- silicon vacancy (1)
- silyl selenides (1)
- silyl sulfides (1)
- simulated digestion (1)
- simultaneous integrated boost (1)
- single photon emission (1)
- single photon emission computed tomography (SPECT) (1)
- single-cell RNA-seq (1)
- single-electron transistors (1)
- single-photon detectors (1)
- single-port appendectomy (1)
- single-sided deafness (1)
- sitting (1)
- skilled forelimb movements (1)
- skin (1)
- skin punch biopsy (1)
- skin squamous cell carcinoma (1)
- skin-to-skin contact (1)
- sleep (1)
- sleep bruxism (1)
- sleep/activity (1)
- sleeve gastrectomy (1)
- small animal (1)
- small-fiber neuropathy (1)
- smart charging (1)
- smart grid (1)
- smart speakers (1)
- smart-phone (1)
- smartwatch (1)
- snow cover area (1)
- snow cover depletion (1)
- social VR (1)
- social attention (1)
- social avoidance (1)
- social cognition (1)
- social cues (1)
- social decision-making (1)
- social distancing (1)
- social identity (1)
- social interaction (1)
- social isolation (1)
- social media (1)
- social motives (1)
- social neuroscience (1)
- social robot (1)
- social robotics (1)
- social support (1)
- socially interactive agents (1)
- sociomotor control (1)
- sodium alginate (1)
- software library (1)
- soil water content (1)
- sol-gel chemistry (1)
- solid-state NMR (1)
- solitary bees (1)
- soluble endoglin (1)
- solvatochromism (1)
- solvent effects (1)
- somatic hypermutation (1)
- somatic mutations (1)
- sound localization (1)
- sown flower field age and size (1)
- space-for-time approach (1)
- spacer (1)
- spatial analysis (1)
- spatial planning (1)
- spatial scales (1)
- spatially structured population (1)
- spatio-temporal analysis (1)
- special schools (1)
- species (1)
- species community composition (1)
- species distribution modeling (1)
- species richness (1)
- species-specific epigenetic marks (1)
- spectral diversity (1)
- spectral karyotyping (1)
- spectral mixture analysis (1)
- spectral statistics (1)
- spectral variation hypothesis (1)
- spectrophotometer (1)
- sperm DNA methylation (1)
- sphingolipid (1)
- sphingosine kinase inhibitor SKI-II (1)
- spillovers (1)
- spin lock (1)
- spin polarization (1)
- spin-lock (1)
- spinal dorsal horn (1)
- spiral ganglion neuron (1)
- spiritual communities (1)
- spontaneous network activity (1)
- spontaneous pneumomediastinum (1)
- spontaneous pneumopericardium (1)
- sport geography (1)
- sport medicine (1)
- spray‐drying (1)
- squamous tumors (1)
- stability (1)
- stable isotope breath tests (1)
- staging (1)
- stalk cell (1)
- standardized analysis method (1)
- standardized reporting system (1)
- staphylocccal infection/epidemiology (1)
- starazine (1)
- starphene analogue (1)
- statin (1)
- steatosis (1)
- stem cell niche (1)
- stenosis (1)
- stent (1)
- stent retriever (1)
- stent-retriever device (1)
- stereology (1)
- stereoselective (1)
- stereotactic irradiation (1)
- stereotypes (1)
- stibinidenes (1)
- stimulated emission (1)
- stock markets (1)
- stomatognatic system (1)
- store-operated Ca2+ entry (1)
- strain elastography (1)
- stress fibers (1)
- stress granules (1)
- stress response (1)
- striatum (1)
- stroke care (1)
- stromal hyaluronan (1)
- stromal tissues (1)
- strong coupling (1)
- structural changes (1)
- structural dynamics (1)
- structural elucidation (1)
- structure (1)
- structure activity (1)
- structure elucidation (1)
- structure prediction (1)
- structured illumination (1)
- structured physical activity (1)
- student performance (1)
- study (1)
- study design (1)
- su-schrieffer-heeger (SSH) models (1)
- sub-pixel coastline extraction (1)
- subcutaneous animal model (1)
- substantia nigra pars compacta (1)
- substituent (1)
- subthalamic nucleus (1)
- subthalamic nucleus (STN) (1)
- successive approximations strategy (1)
- summer precipitation regions (1)
- sun exposure (1)
- sunburn (1)
- super-obesity (1)
- superconducting instability (1)
- superradiance (1)
- supervisors (1)
- supine hypotensive syndrome (1)
- suppressive function (1)
- supramolecular chemistry (1)
- supraparticles (1)
- surface dose measurement (1)
- surface structure (1)
- surface urban heat island (SUHI) (1)
- surface water (1)
- surface water area (1)
- surgical drainage (1)
- surgical management (1)
- surgical management of paraganglioma (1)
- surgical manipulator (1)
- surgical site infection (1)
- surgical therapy (1)
- survey instrument (1)
- sustainability teaching (1)
- sustainable energy source (1)
- sustainable lifestyles (1)
- swarming (1)
- switching (1)
- synapse (1)
- synaptic inhibition (1)
- synaptic ultrastructure (1)
- synthesis (1)
- synthetic aperture RADAR (1)
- system transparency (1)
- systemic effects (1)
- systemic reviews (1)
- systemic therapy (1)
- systems biology (1)
- t-SNE (1)
- tMCAO (1)
- target validation (1)
- targeted combination therapy (1)
- targeted sequencing (1)
- targeted therapies (1)
- targeted therapy (1)
- targeted treatment (1)
- task allocation (1)
- task switching (1)
- tautomerization (1)
- taxane (1)
- teaching materials (1)
- teaching quality (1)
- technology acceptance (1)
- technology-supported education (1)
- technology-supported learning (1)
- teeth (1)
- teeth extraction (1)
- telemedicine network (1)
- temperate forests (1)
- temperature (1)
- temperature gradient (1)
- temporal bone (1)
- temporal range (1)
- temporal statistics (1)
- tendon (1)
- ternary organic solar cells (1)
- terror attacks (1)
- testing-method consensus (1)
- testosterone (1)
- tethering (1)
- tetracoordinated boron (1)
- tetraspanin (1)
- text supervision (1)
- texture analysis (1)
- the sacred (1)
- theoretical and contrastive linguistics (1)
- theory (1)
- therapeutic application (1)
- therapeutic drug monitoring (1)
- thermal point cloud (1)
- thermal rearrangement (1)
- thermodynamics (1)
- thermoelectric characterization (1)
- thermoelectric generators (1)
- thiol-ene (1)
- thiolysis (1)
- thiosemicarbazone (1)
- thorax (1)
- threat (1)
- three-dimensional imaging (1)
- three-dimensional printing (1)
- three-point bending (1)
- threshold indicator taxa analysis (1)
- thrombo-inflammation (1)
- thrombus (1)
- thrust vector control (1)
- thulium telluride (1)
- thymocytes (1)
- thyroid gland (1)
- thyroid hormone (1)
- thyroiditis (1)
- tibial rotation (1)
- tight junctions (1)
- tight-binding (1)
- time geography (1)
- time series analysis (1)
- time-resolved impulsive stimulated raman spectroscopy (1)
- titanium trauma splint (TTS) removal (1)
- tocilizumab (1)
- toll-like receptors (1)
- tongue pressing (1)
- tooth discoloration (1)
- tooth extraction (1)
- tooth loss (1)
- topography (1)
- topological insulators (1)
- topological phase transitions (1)
- topological states (1)
- total hip arthroplasty (1)
- total knee replacement (1)
- totally implantable venous access port (1)
- trabectedin (1)
- tracheotomy (1)
- training (1)
- trait activation in two-stage ultimatum game, (1)
- trait emotional intelligence (1)
- trametinib (1)
- tranexamic acid (1)
- trans-tango (1)
- transcranial direct current stimulation (1)
- transcription factors (1)
- transcriptional control (1)
- transcriptional regulation (1)
- transcriptome (1)
- transcriptomes (1)
- transcriptomic analysis (1)
- transcriptomic response (1)
- transforming growth factor-beta 1 (1)
- transfusion (1)
- transgenic mice (1)
- transient absorption (1)
- transient bursting (1)
- transient regulatory T-cell targeting (1)
- transition metal dichalcogenide (1)
- transition metal dichalcogenides (1)
- transition metal oxides (1)
- translation (1)
- transmission (1)
- transparent matrix (1)
- transporter (1)
- transportome (1)
- trans‐Tango (1)
- trap selectivity (1)
- traumatic brain injury (1)
- treatment (1)
- treatment benefit (1)
- treatment outcome (1)
- treatment plan (1)
- treatment resistance (1)
- trends (1)
- triage (1)
- trial protocol (1)
- triangle method (1)
- triangular fibrocartilage complex (1)
- triarylborane (1)
- triazolotriazine derivatives (1)
- tricompartmental knee osteoarthritis (1)
- triglycerides (1)
- triplet (1)
- triplet sensitization (1)
- truck detection (1)
- trust (1)
- tryptophan hydroxylase-2 (Tph2) (1)
- tubular constructs (1)
- tumor (1)
- tumor microenvironment (1)
- tumor model systems (1)
- tumor necrosis factor alpha (1)
- tumor slice cultures (1)
- tumor-associated hyaluronan staining pattern (1)
- two-dimensional materials (1)
- two-dimensions (1)
- two-photon absorption (1)
- two-stage ultimatum game (1)
- two‐sided markets (1)
- two‑layer feedforward networks (1)
- tympanic paraganglioma (1)
- tympanojugular paraganglioma (1)
- tyrosine kinase (1)
- tyrosine-kinase inhibitor (1)
- ubiquitination (1)
- ultrafast Raman loss spectroscopy (1)
- ultrasound imaging (1)
- uncertain volatility (1)
- uncertainty quantification (1)
- unconventional superconductivity (1)
- under-dosing (1)
- undernourishment (1)
- undersampling (1)
- unexpressed needs (1)
- unfolded protein response (1)
- unilateral hearing loss (1)
- universal prevention (1)
- unmanned aerial vehicles (1)
- urban (1)
- urban climate (1)
- urban ecology (1)
- urban modelling (1)
- uremic toxins (1)
- urgent surgery (1)
- user acceptance (1)
- uveal melanoma (1)
- vaccination (1)
- vaccine hesitancy (1)
- vancomycin (1)
- variable regions (1)
- variant (1)
- vasa vasorum (1)
- vascular access (1)
- vascular homeostasis (1)
- vascularized scaffold (1)
- vasculogenesis (1)
- vection (1)
- vegetation indices (1)
- vegetation restoration (1)
- vemurafenib (1)
- verbal humor (1)
- vertebral artery (1)
- verteporfin (1)
- vertical stratification (1)
- vessel diameter (1)
- vessel tapering (1)
- vestibular (1)
- vestibular aqueduct (VA) (1)
- vibrational coherence (1)
- vigorous intermittent lifestyle physical activities (1)
- viral infection (1)
- viral pathology (1)
- virtual (1)
- virtual agent (1)
- virtual body ownership (1)
- virtual docking (1)
- virtual hand illusion (1)
- virtual human (1)
- virtual noncalcium imaging (1)
- virtual stimuli (1)
- virtual tunnel (1)
- virulence (1)
- virus (1)
- viruses (1)
- visual activity (1)
- visual clustering (1)
- visual pathways (1)
- visual system (1)
- visualization of technology (1)
- vitamin C (1)
- vitamin D receptor (1)
- vitamin D3 (cholecalciferol, VD3) (1)
- volcanoes (1)
- voltage-gated Na\(^+\) channel (1)
- volume (1)
- volume clamp (1)
- volume regulation (1)
- volumetric absorptive micro-sampling (VAMS) (1)
- volumetric modulated arc therapy (VMAT) (1)
- vulnerability (1)
- vulnerability paradox (1)
- vulnerance (1)
- walking (1)
- water (1)
- wax composition (1)
- weak coupling (1)
- wearable (1)
- weight bearing line (1)
- well-being (1)
- white blood cell count (1)
- white matter hyperintensities (1)
- whole genome sequencing (1)
- whole genome sequencing (WGS) (1)
- whole-exome sequencing (1)
- wild honeybees (1)
- wood anatomy (1)
- wood density (1)
- word-formation (1)
- workflow (1)
- wound (1)
- wound healing (1)
- wound infection (1)
- x-ray computed (1)
- yoga (1)
- younger employees (1)
- zebrafish (1)
- zircon geochronology (1)
- zoledronic acid (1)
- zygomorphy (1)
- α-Particle (1)
- α-synuclein-specific T cells (1)
- α‐diversity (1)
- β-actin mRNA (1)
- β-adrenergic receptors (1)
- βAR (1)
- β‐diversity (1)
- γ-H2AX (1)
- γδ T cell (1)
- γδ T cells (1)
- π-extension (1)
- “other-power” (1)
Institute
- Theodor-Boveri-Institut für Biowissenschaften (108)
- Medizinische Klinik und Poliklinik I (52)
- Neurologische Klinik und Poliklinik (51)
- Medizinische Klinik und Poliklinik II (48)
- Klinik und Poliklinik für Anästhesiologie (ab 2004) (41)
- Institut für Geographie und Geologie (39)
- Comprehensive Cancer Center Mainfranken (35)
- Institut für Informatik (35)
- Lehrstuhl für Orthopädie (33)
- Klinik und Poliklinik für Nuklearmedizin (32)
Sonstige beteiligte Institutionen
- IZKF Nachwuchsgruppe Geweberegeneration für muskuloskelettale Erkrankungen (5)
- Bernhard-Heine-Centrum für Bewegungsforschung (4)
- Zentraleinheit Klinische Massenspektrometrie (3)
- Krankenhaushygiene und Antimicrobial Stewardship (Universitätsklinikum) (2)
- Wilhelm-Conrad-Röntgen-Forschungszentrum für komplexe Materialsysteme (2)
- Arizona State University, Tempe, Arizona, USA (1)
- Clinical Trial Center (CTC) / Zentrale für Klinische Studien Würzburg (ZKSW) (1)
- Cluster of Excellence "Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells, Göttingen (1)
- Datenintegrationszentrum Würzburg (DIZ) (1)
- Department of Cellular Biochemistry, University Medical Centre Göttingen (1)
Husserl’s taxonomy of action
(2022)
In the present article I discuss, in confrontation with the most recent studies on Husserl’s phenomenology of acting and willing, the taxonomy of action that is collected in the volume ‘Wille und Handlung’ of the Husserliana edition Studien zur Struktur des Bewussteins. In so doing, I first present Husserl’s universal characterization of action (Handlung) as a volitional process (willentlicher Vorgang). Then, after clarifying what it means for a process to have a character of volitionality (Willentlichkeit), I illustrate the various types of actions, which Husserl distinguishes as ‘straightforward’ (schlicht) or ‘deciding’ (entscheidend), ‘primary’ (primär) or ‘secondary’ (sekundär), ‘inner’ (innere) or ‘outer’ (äußere), ‘immediate’ (unmittelbar) or mediate (mittelbar), ‘simple’ (einfach) or ‘compound’ (zusammengesetzt). Finally, I consider Husserl’s discussion of the direction and foundation of action.
Unisexual reproduction, which generates clonal offspring, is an alternative strategy to sexual breeding and occurs even in vertebrates. A wide range of non-sexual reproductive modes have been described, and one of the least understood questions is how such pathways emerged and how they mechanistically proceed. The Amazon molly, Poecilia formosa, needs sperm from males of related species to trigger the parthenogenetic development of diploid eggs. However, the mechanism, of how the unreduced female gametes are produced, remains unclear. Cytological analyses revealed that the chromosomes of primary oocytes initiate pachytene but do not proceed to bivalent formation and meiotic crossovers. Comparing ovary transcriptomes of P. formosa and its sexual parental species revealed expression levels of meiosis-specific genes deviating from P. mexicana but not from P. latipinna. Furthermore, several meiosis genes show biased expression towards one of the two alleles from the parental genomes. We infer from our data that in the Amazon molly diploid oocytes are generated by apomixis due to a failure in the synapsis of homologous chromosomes. The fact that this failure is not reflected in the differential expression of known meiosis genes suggests the underlying molecular mechanism may be dysregulation on the protein level or misexpression of a so far unknown meiosis gene, and/or hybrid dysgenesis because of compromised interaction of proteins from diverged genomes.
Higher temperatures can increase metabolic rates and carbon demands of invertebrate herbivores, which may shift leaf-chewing herbivory among plant functional groups differing in C:N (carbon:nitrogen) ratios. Biotic factors influencing herbivore species richness may modulate these temperature effects. Yet, systematic studies comparing leaf-chewing herbivory among plant functional groups in different habitats and landscapes along temperature gradients are lacking. This study was conducted on 80 plots covering large gradients of temperature, plant richness and land use in Bavaria, Germany. We investigated proportional leaf area loss by chewing invertebrates (‘herbivory’) in three plant functional groups on open herbaceous vegetation. As potential drivers, we considered local mean temperature (range 8.4–18.8 °C), multi-annual mean temperature (range 6.5–10.0 °C), local plant richness (species and family level, ranges 10–51 species, 5–25 families), adjacent habitat type (forest, grassland, arable field, settlement), proportion of grassland and landscape diversity (0.2–3 km scale). We observed differential responses of leaf-chewing herbivory among plant functional groups in response to plant richness (family level only) and habitat type, but not to grassland proportion, landscape diversity and temperature—except for multi-annual mean temperature influencing herbivory on grassland plots. Three-way interactions of plant functional group, temperature and predictors of plant richness or land use did not substantially impact herbivory. We conclude that abiotic and biotic factors can assert different effects on leaf-chewing herbivory among plant functional groups. At present, effects of plant richness and habitat type outweigh effects of temperature and landscape-scale land use on herbivory among legumes, forbs and grasses.
Government funding of research beyond biomedicine: challenges and opportunities for neuroethology
(2022)
Curiosity-driven research is fundamental for neuroethology and depends crucially on governmental funding. Here, we highlight similarities and differences in funding of curiosity-driven research across countries by comparing two major funding agencies—the National Science Foundation (NSF) in the United States and the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG). We interviewed representatives from each of the two agencies, focusing on general funding trends, levels of young investigator support, career-life balance, and international collaborations. While our analysis revealed a negative trend in NSF funding of biological research, including curiosity-driven research, German researchers in these areas have benefited from a robust positive trend in DFG funding. The main reason for the decrease in curiosity-driven research in the US is that the NSF has only partially been able to compensate for the funding gap resulting from the National Institutes of Health restricting their support to biomedical research using select model organisms. Notwithstanding some differences in funding programs, particularly those relevant for scientists in the postdoctoral phase, both the NSF and DFG clearly support curiosity-driven research.
Recent analyses conducted by German official food control reported detection of the aromatic amides N-(2,4-dimethylphenyl)acetamide (NDPA), N-acetoacetyl-m-xylidine (NAAX) and 3-hydroxy-2-naphthanilide (Naphthol AS) in cold water extracts from certain food contact materials made from paper or cardboard, including paper straws, paper napkins, and cupcake liners. Because aromatic amides may be cleaved to potentially genotoxic primary amines upon oral intake, these findings raise concern that transfer of NDPA, NAAX and Naphthol AS from food contact materials into food may present a risk to human health. The aim of the present work was to assess the stability of NDPA, NAAX and Naphthol AS and potential cleavage to 2,4-dimethylaniline (2,4-DMA) and aniline during simulated passage through the gastrointestinal tract using static in vitro digestion models. Using the digestion model established by the National Institute for Public Health and the Environment (RIVM, Bilthoven, NL) and a protocol recommended by the European Food Safety Authority, potential hydrolysis of the aromatic amides to the respective aromatic amines was assessed by LC–MS/MS following incubation of the aromatic amides with digestive fluid simulants. Time-dependent hydrolysis of NDPA and NAAX resulting in formation of the primary aromatic amine 2,4-DMA was consistently observed in both models. The highest rate of cleavage of NDPA and NAAX was recorded following 4 h incubation with 0.07 M HCl as gastric-juice simulant, and amounted to 0.21% and 0.053%, respectively. Incubation of Naphthol AS with digestive fluid simulants did not give rise to an increase in the concentration of aniline above the background that resulted from the presence of aniline as an impurity of the test compound. Considering the lack of evidence for aniline formation from Naphthol AS and the extremely low rate of hydrolysis of the amide bonds of NDPA and NAAX during simulated passage through the gastrointestinal tract that gives rise to only very minor amounts of the potentially mutagenic and/or carcinogenic aromatic amine 2,4-DMA, risk assessment based on assumption of 100% cleavage to the primary aromatic amines would appear to overestimate health risks related to the presence of aromatic amides in food contact materials.
The subclassification of diffuse large B-cell lymphoma (DLBCL) into germinal center B-cell-like (GCB) and activated B-cell-like (ABC) subtypes has become mandatory in the 2017 update of the WHO classification of lymphoid neoplasms and will continue to be used in the WHO 5\(^{th}\) edition. The RNA-based Lymph2Cx assay has been validated as a reliable surrogate of high-throughput gene expression profiling assays for distinguishing between GCB and ABC DLBCL and provides reliable results from formalin-fixed, paraffin-embedded (FFPE) material. This test has been previously used in clinical trials, but experience from real-world routine application is rare. We routinely applied the Lymph2Cx assay to day-to-day diagnostics on a series of 147 aggressive B-cell lymphoma cases and correlated our results with the immunohistochemical subclassification using the Hans algorithm and fluorescence in situ hybridization findings using break-apart probes for MYC, BCL2, and BCL6. The routine use of the Lymph2Cx assay had a high technical success rate (94.6%) with a low rate of failure due to poor material and/or RNA quality. The Lymph2Cx assay was discordant with the Hans algorithm in 18% (23 of 128 cases). Discordant cases were mainly classified as GCB by the Hans algorithm and as ABC by Lymph2Cx (n = 11, 8.6%). Only 5 cases (3.9%) were classified as non-GCB by the Hans algorithm and as GCB by Lymph2Cx. Additionally, 5.5% of cases (n = 7) were left unclassified by Lymph2Cx, whereas they were defined as GCB (n = 4) or non-GCB (n = 3) by the Hans algorithm. Our data support the routine applicability of the Lymph2Cx assay.
Lower limb bone geometry in adult individuals with X-linked hypophosphatemia: an observational study
(2022)
Summary
We assessed lower-limb geometry in adults with X-linked hypophosphatemia (XLH) and controls. We found large differences in multiple measures including femoral and tibial torsion, bowing and cross-sectional area and acetabular version and coverage which may contribute to clinical problems such as osteoarthritis, fractures and altered gait common in XLH.
Purpose
Individuals with X-linked hypophosphatemia (XLH) are at risk of lower-limb deformities and early onset of osteoarthritis. These two factors may be linked, as altered biomechanics is a risk factor for osteoarthritis. This exploratory evaluation aims at providing clues and concepts for this association to facilitate future larger-scale and longitudinal studies on that aspect.
Methods
For this observational study, 13 patients with XLH, aged 18–65 years (6 female), were compared with sex-, age- and weight-matched healthy individuals at a single German research centre. Femoral and hip joint geometry, including femoral and tibial torsion and femoral and tibial shaft bowing, bone cross-sectional area (CSA) and acetabular version and coverage were measured from magnetic resonance imaging (MRI) scans.
Results
Total femoral torsion was 29° lower in individuals with XLH than in controls (p < 0.001), mainly resulting from lower intertrochanteric torsion (ITT) (p < 0.001). Femoral lateral and frontal bowing, tibial frontal bowing, mechanical axis, femoral mechanical–anatomical angle, acetabular version and acetabular coverage were all greater and tibial torsion lower in individuals with XLH as compared to controls (all p < 0.05). Greater femoral total and marrow cavity CSA, greater tibial marrow cavity CSA and lower cortical CSA were observed in XLH (all p < 0.05).
Discussion
We observed large differences in clinically relevant measures of tibia and particularly femur bone geometry in individuals with XLH compared to controls. These differences may plausibly contribute to clinical manifestations of XLH such as early-onset osteoarthritis, pseudofractures and altered gait and therefore should be considered when planning corrective surgeries.
Purpose of Review
Statins are routinely applied in patients with coronary artery disease, as they allow significantly to reduce blood cholesterol levels. Although those drugs are endorsed by current guidelines and prescribed routinely, a substantial portion of patients are still statin-intolerant and image-piloted strategies may then be helpful to identify patients that need further intensified treatment, e.g., to initiate treatment with proprotein convertase subtilisin / kexin type 9 inhibitors (PCSK9i). In addition, it has also been advocated that statins exhibit nonlipid, cardio-protective effects including improved cardiac nerve integrity, blood flow, and anti-inflammatory effects in congestive heart failure (HF) patients.
Recent Findings
In subjects after myocardial infarction treated with statins, \(^{123}\)I-metaiodobenzylguanidine (MIBG) scintigraphy has already revealed enhanced cardiac nerve function relative to patients without statins. In addition, all of those aforementioned statin-targeted pathways in HF can be visualized and monitored using dedicated cardiac radiotracers, e.g., \(^{123}\)I-MIBG or \(^{18}\)F-AF78 (for cardiac nerve function), \(^{18}\)F-flurpiridaz (to determine coronary flow) or \(^{68}\)Ga-PentixaFor (to detect inflammation).
Summary
Statins exhibit various cardio-beneficial effects, including improvement of cardiac nerve function, blood flow, and reduction of inflammation, which can all be imaged using dedicated nuclear cardiac radiotracers. This may allow for in vivo monitoring of statin-induced cardioprotection beyond lipid profiling in HF patients.
Introduction
In men with metastatic castration-resistant prostate cancer (mCRPC) scheduled for prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT), biochemical response is assessed based on repeated measurements of prostate-specific antigen (PSA) levels. We aimed to determine overall survival (OS) in patients experiencing sustained PSA increase, decrease, or fluctuations during therapy.
Materials and methods
In this bicentric study, we included 176 mCRPC patients treated with PSMA-directed RLT. PSA levels were determined using blood samples prior to the first RLT and on the admission days for the following cycles. We calculated relative changes in PSA levels compared to baseline. Kaplan–Meier curves as well as log-rank test were used to compare OS of different subgroups, including patients with sustained PSA increase, decrease, or fluctuations (defined as change after initial decrease or increase after the first cycle).
Results
Sixty-one out of one hundred seventy-six (34.7%) patients showed a sustained increase and 86/176 (48.8%) a sustained decrease in PSA levels. PSA fluctuations were observed in the remaining 29/176 (16.5%). In this subgroup, 22/29 experienced initial PSA decrease followed by an increase (7/29, initial increase followed by a decrease). Median OS of patients with sustained decrease in PSA levels was significantly longer when compared to patients with sustained increase of PSA levels (19 vs. 8 months; HR 0.35, 95% CI 0.22–0.56; P < 0.001). Patients with PSA fluctuations showed a significantly longer median OS compared to patients with sustained increase of PSA levels (18 vs. 8 months; HR 0.49, 95% CI 0.30–0.80; P < 0.01), but no significant difference relative to men with sustained PSA decrease (18 vs. 19 months; HR 1.4, 95% CI 0.78–2.49; P = 0.20). In addition, in men experiencing PSA fluctuations, median OS did not differ significantly between patients with initial decrease or initial increase of tumor marker levels (16 vs. 18 months; HR 1.2, 95% CI 0.38–4.05; P = 0.68).
Conclusion
Initial increase or decrease of PSA levels is sustained in the majority of patients undergoing RLT. Sustained PSA decrease was linked to prolonged survival and men with PSA fluctuations under treatment experienced comparable survival benefits. As such, transient tumor marker oscillations under RLT should rather not lead to treatment discontinuation, especially in the absence of radiological progression.
Purpose
As α-emitters for radiopharmaceutical therapies are administered systemically by intravenous injection, blood will be irradiated by α-particles that induce clustered DNA double-strand breaks (DSBs). Here, we investigated the induction and repair of DSB damage in peripheral blood mononuclear cells (PBMCs) as a function of the absorbed dose to the blood following internal ex vivo irradiation with [\(^{223}\)Ra]RaCl2.
Methods
Blood samples of ten volunteers were irradiated by adding [\(^{223}\)Ra]RaCl2 solution with different activity concentrations resulting in absorbed doses to the blood of 3 mGy, 25 mGy, 50 mGy and 100 mGy. PBMCs were isolated, divided in three parts and either fixed directly (d-samples) or after 4 h or 24 h culture. After immunostaining, the induced γ-H2AX α-tracks were counted. The time-dependent decrease in α-track frequency was described with a model assuming a repair rate R and a fraction of non-repairable damage Q.
Results
For 25 mGy, 50 mGy and 100 mGy, the numbers of α-tracks were significantly increased compared to baseline at all time points. Compared to the corresponding d-samples, the α-track frequency decreased significantly after 4 h and after 24 h. The repair rates R were (0.24 ± 0.05) h−1 for 25 mGy, (0.16 ± 0.04) h−1 for 50 mGy and (0.13 ± 0.02) h−1 for 100 mGy, suggesting faster repair at lower absorbed doses, while Q-values were similar.
Conclusion
The results obtained suggest that induction and repair of the DSB damage depend on the absorbed dose to the blood. Repair rates were similar to what has been observed for irradiation with low linear energy transfer.
Background
Radioligand therapy (RLT) with \(^{177}\)Lu-labeled prostate-specific membrane antigen (PSMA) ligands is associated with prolonged overall survival (OS) in patients with advanced, metastatic castration-resistant prostate cancer (mCRPC). A substantial number of patients, however, are prone to treatment failure. We aimed to determine clinical baseline characteristics to predict OS in patients receiving [\(^{177}\)Lu]Lu-PSMA I&T RLT in a long-term follow-up.
Materials and methods
Ninety-two mCRPC patients treated with [\(^{177}\)Lu]Lu-PSMA I&T with a follow-up of at least 18 months were retrospectively identified. Multivariable Cox regression analyses were performed for various baseline characteristics, including laboratory values, Gleason score, age, prior therapies, and time interval between initial diagnosis and first treatment cycle (interval\(_{Diagnosis-RLT}\), per 12 months). Cutoff values for significant predictors were determined using receiver operating characteristic (ROC) analysis. ROC-derived thresholds were then applied to Kaplan–Meier analyses.
Results
Baseline C-reactive protein (CRP; hazard ratio [HR], 1.10, 95% CI 1.02–1.18; P = 0.01), lactate dehydrogenase (LDH; HR, 1.07, 95% CI 1.01–1.11; P = 0.01), aspartate aminotransferase (AST; HR, 1.16, 95% CI 1.06–1.26; P = 0.001), and interval\(_{Diagnosis-RLT}\) (HR, 0.95, 95% CI 0.91–0.99; P = 0.02) were identified as independent prognostic factors for OS. The following respective ROC-based thresholds were determined: CRP, 0.98 mg/dl (area under the curve [AUC], 0.80); LDH, 276.5 U/l (AUC, 0.83); AST, 26.95 U/l (AUC, 0.73); and interval\(_{Diagnosis-RLT}\), 43.5 months (AUC, 0.68; P < 0.01, respectively). Respective Kaplan–Meier analyses demonstrated a significantly longer median OS of patients with lower CRP, lower LDH, and lower AST, as well as prolonged interval\(_{Diagnosis-RLT}\) (P ≤ 0.01, respectively).
Conclusion
In mCRPC patients treated with [\(^{177}\)Lu]Lu-PSMA I&T, baseline CRP, LDH, AST, and time interval until RLT initiation (thereby reflecting a possible indicator for tumor aggressiveness) are independently associated with survival. Our findings are in line with previous findings on [\(^{177}\)Lu]Lu-PSMA-617, and we believe that these clinical baseline characteristics may support the nuclear medicine specialist to identify long-term survivors.
A growing body of literature reports on the upregulation of C-X-C motif chemokine receptor 4 (CXCR4) in a variety of cancer entities, rendering this receptor as suitable target for molecular imaging and endoradiotherapy in a theranostic setting. For instance, the CXCR4-targeting positron emission tomography (PET) agent [\(^{68}\)Ga]PentixaFor has been proven useful for a comprehensive assessment of the current status quo of solid tumors, including adrenocortical carcinoma or small-cell lung cancer. In addition, [\(^{68}\)Ga]PentixaFor has also provided an excellent readout for hematological malignancies, such as multiple myeloma, marginal zone lymphoma, or mantle cell lymphoma. PET-based quantification of the CXCR4 capacities in vivo allows for selecting candidates that would be suitable for treatment using the theranostic equivalent [\(^{177}\)Lu]/[\(^{90}\)Y]PentixaTher. This CXCR4-directed theranostic concept has been used as a conditioning regimen prior to hematopoietic stem cell transplantation and to achieve sufficient anti-lymphoma/-tumor activity in particular for malignant tissues that are highly sensitive to radiation, such as the hematological system. Increasing the safety margin, pretherapeutic dosimetry is routinely performed to determine the optimal activity to enhance therapeutic efficacy and to reduce off-target adverse events. The present review will provide an overview of current applications for CXCR4-directed molecular imaging and will introduce the CXCR4-targeted theranostic concept for advanced hematological malignancies.
Risperidone is commonly used to treat different psychiatric disorders worldwide. Knowledge on dose–concentration relationships of risperidone treatment in children and adolescents with schizophrenia or other psychotic disorders is, however, scarce and no age-specific therapeutic ranges have been established yet. Multicenter data of a therapeutic drug monitoring service were analyzed to evaluate the relationship between risperidone dose and serum concentration of the active moiety (risperidone (RIS) plus its main metabolite 9-hydroxyrisperidone (9-OH-RIS)) in children and adolescents with psychotic disorders. Patient characteristics, doses, serum concentrations and therapeutic outcomes were assessed by standardized measures. The study also aimed to evaluate whether the therapeutic reference range for adults (20–60 ng/ml) is applicable for minors. In the 64 patients (aged 11–18 years) included, a positive correlation between daily dose and the active moiety (RIS\(_{am}\)) concentration was found (r\(_s\) = 0.49, p = 0.001) with variation in dose explaining 24% (r\(_s\)\(^2\) = 0.240) of the variability in serum concentrations. While the RIS\(_{am}\) concentration showed no difference, RIS as well 9-OH-RIS concentrations and the parent to metabolite ratio varied significantly in patients with co-medication of a CYP2D6 inhibitor. Patients with extrapyramidal symptoms (EPS) had on average higher RIS\(_{am}\) concentrations than patients without (p = 0.05). Considering EPS, the upper threshold of the therapeutic range of RIS\(_{am}\) was determined to be 33 ng/ml. A rough estimation method also indicated a possibly decreased lower limit of the preliminary therapeutic range in minors compared to adults. These preliminary data may contribute to the definition of a therapeutic window in children and adolescents with schizophrenic disorders treated with risperidone. TDM is recommended in this vulnerable population to prevent concentration-related adverse drug reactions.
Purpose
To evaluate the technical and clinical outcome of Sinus-XL stent placement in patients with malignant obstruction syndrome of the inferior vena cava.
Methods
Between October 2010 and January 2021, 21 patients with different malignant primary disease causing inferior vena cava obstruction were treated with Sinus-XL stent implantation. Procedural data, technical and clinical outcome parameters were retrospectively analyzed.
Results
Technical success was 100%. Analysis of available manometry data revealed a significant reduction of the mean translesional pressure gradient following the procedure (p = 0.008). Reintervention rate was 4.8% (1/21). The available follow-up imaging studies showed primary and primary-assisted stent patency rates of 93% (13/14) and 100% (14/14), respectively. Major complications did not occur. The clinical success regarding lower extremity edema was 82.4% (14/17) for the first and 85.7% (18/21) for the last follow-up. Longer lengths of IVC obstruction were associated with reduced clinical improvement after the procedure (p = 0.025). Improvement of intraprocedural manometry results and lower extremity edema revealed only minor correlation. Ascites and anasarca were not significantly positively affected by the procedure.
Conclusion
Sinus-XL stent placement in patients with malignant inferior vena cava obstruction showed high technical success and low complication rates. Regarding the clinical outcome, significant symptom improvement could be achieved in lower extremity edema, whereas ascites and anasarca lacked satisfying symptom relief. Based on our results, this procedure should be considered as a suitable therapy in a palliative care setting for patients with advanced malignant disease.
It’s time to go …
(2022)
In task-switching studies, performance is typically worse in task-switch trials than in task-repetition trials. These switch costs are often asymmetrical, a phenomenon that has been explained by referring to a dominance of one task over the other. Previous studies also indicated that response modalities associated with two tasks may be considered as integral components for defining a task set. However, a systematic assessment of the role of response modalities in task switching is still lacking: Are some response modalities harder to switch to than others? The present study systematically examined switch costs when combining tasks that differ only with respect to their associated effector systems. In Experiment 1, 16 participants switched (in unpredictable sequence) between oculomotor and vocal tasks. In Experiment 2, 72 participants switched (in pairwise combinations) between oculomotor, vocal, and manual tasks. We observed systematic performance costs when switching between response modalities under otherwise constant task features and could thereby replicate previous observations of response modality switch costs. However, we did not observe any substantial switch-cost asymmetries. As previous studies using temporally overlapping dual-task paradigms found substantial prioritization effects (in terms of asymmetric costs) especially for oculomotor tasks, the present results suggest different underlying processes in sequential task switching than in simultaneous multitasking. While more research is needed to further substantiate a lack of response modality switch-cost asymmetries in a broader range of task switching situations, we suggest that task-set representations related to specific response modalities may exhibit rapid decay.
Evidence from multisensory body illusions suggests that body representations may be malleable, for instance, by embodying external objects. However, adjusting body representations to current task demands also implies that external objects become disembodied from the body representation if they are no longer required. In the current web-based study, we induced the embodiment of a two-dimensional (2D) virtual hand that could be controlled by active movements of a computer mouse or on a touchpad. Following initial embodiment, we probed for disembodiment by comparing two conditions: Participants either continued moving the virtual hand or they stopped moving and kept the hand still. Based on theoretical accounts that conceptualize body representations as a set of multisensory bindings, we expected gradual disembodiment of the virtual hand if the body representations are no longer updated through correlated visuomotor signals. In contrast to our prediction, the virtual hand was instantly disembodied as soon as participants stopped moving it. This result was replicated in two follow-up experiments. The observed instantaneous disembodiment might suggest that humans are sensitive to the rapid changes that characterize action and body in virtual environments, and hence adjust corresponding body representations particularly swiftly.
Background
Children with different underlying malignant diseases require long-term central venous access. As for port systems in a pectoral position, peripherally implanted port systems in the forearm revealed high levels of technical and clinical success in adult cohorts.
Objective
To investigate the technical and clinical outcomes of percutaneous central venous port implantation in the forearm in adolescents.
Materials and methods
Between April 2010 and August 2020, 32 children ages 9 to 17 years with underlying malignancy received 35 totally implantable venous access ports (TIVAPs) in the forearm. All venous port systems were peripherally inserted under ultrasound guidance. Correct catheter placement was controlled by fluoroscopy. As primary endpoints, the technical success, rate of complications and catheter maintenance were analyzed. Secondary endpoints were the side of implantation, vein of catheter access, laboratory results on the day of the procedure, procedural radiation exposure, amount of contrast agent and reasons for port device removal.
Results
Percutaneous TIVAP placement under sonographic guidance was technically successful in 34 of 35 procedures (97.1%). Procedure-related complications did not occur. During the follow-up, 13,684 catheter days were analyzed, revealing 11 complications (0.8 per 1,000 catheter-duration days), Of these 11 complications, 7 were major and 10 occurred late. In seven cases, the port device had to be removed; removal-related complications did not occur.
Conclusion
Peripheral TIVAP placement in the forearms of children is a feasible, effective and safe technique with good midterm outcome. As results are comparable with standard access routes, this technique may be offered as an alternative when intermittent venous access is required.
Objective
Multipartite epicondyles may mimic fractures in the setting of pediatric elbow trauma. This study examines the prevalence of multipartite epicondyles during skeletal development and their association with pediatric elbow fractures.
Materials and methods
In this retrospective analysis, 4282 elbow radiographs of 1265 elbows of 1210 patients aged 0–17 years were reviewed. The radiographs were analyzed by two radiologists in consensus reading, and the number of visible portions of the medial and lateral epicondyles was noted. For elbows in which epicondylar ossification was not yet visible, the epicondyles were already fused with the humerus or could not be sufficiently evaluated due to projection issues or because osteosynthesis material was excluded. In total, 187 elbows were included for the lateral and 715 for the medial epicondyle analyses.
Results
No multipartite medial epicondyles were found in patients without history of elbow fracture, whereas 9% of these patients had multipartite lateral epicondyles (p < 0.01). Current or previous elbow fractures increased the prevalence of multipartite epicondyles, with significant lateral predominance (medial epicondyle + 9% vs. lateral + 24%, p < 0.0001). Including all patients regardless of a history of elbow fracture, multipartite medial epicondyles were observed in 3% and multipartite lateral epicondyles in 18% (p < 0.0001). There was no gender difference in the prevalence of multipartition of either epicondyle, regardless of a trauma history.
Conclusion
Multipartite medial epicondyles occur in patients with current or previous elbow fractures only, whereas multipartite lateral epicondyles may be constitutional. Elbow fractures increase the prevalence of multipartite epicondyles on both sides, with significant lateral predominance.
Key Points
• Multipartite medial epicondyles should be considered of traumatic origin.
• Multipartite lateral epicondyles may be constitutional.
• Elbow fractures increase the prevalence of multipartite epicondyles on both sides with lateral predominance.
Purpose
For somatostatin receptor (SSTR)-positron emission tomography/computed tomography (PET/CT), a standardized framework termed SSTR-reporting and data system (RADS) has been proposed. We aimed to elucidate the impact of a RADS-focused training on reader’s anxiety to report on SSTR-PET/CT, the motivational beliefs in learning such a system, whether it increases reader’s confidence, and its implementation in clinical routine.
Procedures
A 3-day training course focusing on SSTR-RADS was conducted. Self-report questionnaires were handed out prior to the course (Pre) and thereafter (Post). The impact of the training on the following categories was evaluated: (1) test anxiety to report on SSTR-PET/CT, (2) motivational beliefs, (3) increase in reader’s confidence, and (4) clinical implementation. To assess the effect size of the course, Cohen’s d was calculated (small, d = 0.20; large effect, d = 0.80).
Results
Of 22 participants, Pre and Post were returned by 21/22 (95.5%). In total, 14/21 (66.7%) were considered inexperienced (IR, < 1 year experience in reading SSTR-PET/CTs) and 7/21 (33.3%) as experienced readers (ER, > 1 year). Applying SSTR-RADS, a large decrease in anxiety to report on SSTR-PET/CT was noted for IR (d = − 0.74, P = 0.02), but not for ER (d = 0.11, P = 0.78). For the other three categories motivational beliefs, reader’s confidence, and clinical implementation, agreement rates were already high prior to the training and persisted throughout the course (P ≥ 0.21).
Conclusions
A framework-focused reader training can reduce anxiety to report on SSTR-PET/CTs, in particular for inexperienced readers. This may allow for a more widespread adoption of this system, e.g., in multicenter trials for better intra- and interindividual comparison of scan results.
Excitons in atomically thin transition-metal dichalcogenides (TMDs) have been established as an attractive platform to explore polaritonic physics, owing to their enormous binding energies and giant oscillator strength. Basic spectral features of exciton polaritons in TMD microcavities, thus far, were conventionally explained via two-coupled-oscillator models. This ignores, however, the impact of phonons on the polariton energy structure. Here we establish and quantify the threefold coupling between excitons, cavity photons, and phonons. For this purpose, we employ energy-momentum-resolved photoluminescence and spatially resolved coherent two-dimensional spectroscopy to investigate the spectral properties of a high-quality-factor microcavity with an embedded WSe\(_2\) van-der-Waals heterostructure at room temperature. Our approach reveals a rich multi-branch structure which thus far has not been captured in previous experiments. Simulation of the data reveals hybridized exciton-photon-phonon states, providing new physical insight into the exciton polariton system based on layered TMDs.
Leaf-cutting ants are highly successful herbivores in the Neotropics. They forage large amounts of fresh plant material to nourish a symbiotic fungus that sustains the colony. It is unknown how workers organize the intra-nest distribution of resources, and whether they respond to increasing demands in some fungus gardens by adjusting the amount of delivered resources accordingly. In laboratory experiments, we analyzed the spatial distribution of collected leaf fragments among nest chambers in Acromyrmex ambiguus leaf-cutting ants, and how it changed when one of the fungus gardens experienced undernourishment. Plant fragments were evenly distributed among nest chambers when the fungal symbiont was well nourished. That pattern changed when one of the fungus gardens was undernourished and had a higher leaf demand, resulting in more leaf discs delivered to the undernourished fungus garden over at least 2 days after deprivation. Some ants bypassed nourished gardens to directly deliver their resource to the chamber with higher nutritional demand. We hypothesize that cues arising from that chamber might be used for orientation and/or that informed individuals, presumably stemming from the undernourished chamber, may preferentially orient to them.
Purpose
Dose-escalated external beam radiation therapy (EBRT) and EBRT + high-dose-rate brachytherapy (HDR-BT) boost are guideline-recommended treatment options for localized prostate cancer. The purpose of this study was to compare long-term outcome and toxicity of dose-escalated EBRT versus EBRT + HDR-BT boost.
Methods
From 2002 to 2019, 744 consecutive patients received either EBRT or EBRT + HDR-BT boost, of whom 516 patients were propensity score matched. Median follow-up was 95.3 months. Cone beam CT image-guided EBRT consisted of 33 fractions of intensity-modulated radiation therapy with simultaneous integrated boost up to 76.23 Gy (D\(_{Mean}\)). Combined treatment was delivered as 46 Gy (D\(_{Mean}\)) EBRT, followed by two fractions HDR-BT boost with 9 Gy (D\(_{90\%}\)). Propensity score matching was applied before analysis of the primary endpoint, estimated 10-year biochemical relapse-free survival (bRFS), and the secondary endpoints metastasis-free survival (MFS) and overall survival (OS). Prognostic parameters were analyzed by Cox proportional hazard modelling. Genitourinary (GU)/gastrointestinal (GI) toxicity evaluation used the Common Toxicity Criteria for Adverse Events (v5.0).
Results
The estimated 10-year bRFS was 82.0% vs. 76.4% (p = 0.075) for EBRT alone versus combined treatment, respectively. The estimated 10-year MFS was 82.9% vs. 87.0% (p = 0.195) and the 10-year OS was 65.7% vs. 68.9% (p = 0.303), respectively. Cumulative 5‑year late GU ≥ grade 2 toxicities were seen in 23.6% vs. 19.2% (p = 0.086) and 5‑year late GI ≥ grade 2 toxicities in 11.1% vs. 5.0% of the patients (p = 0.002); cumulative 5‑year late grade 3 GU toxicity occurred in 4.2% vs. 3.6% (p = 0.401) and GI toxicity in 1.0% vs. 0.3% (p = 0.249), respectively.
Conclusion
Both treatment groups showed excellent long-term outcomes with low rates of severe toxicity.
Routine coronal paraffin-sections through the dorsal frontal and parieto-occipital cortex of a total of sixty cases with divergent causes of death were immunohistochemically (IHC) stained with an antibody against TMEM119. Samples of cerebrospinal fluid (CSF) of the same cases were collected by suboccipital needle-puncture, subjected to centrifugation and processed as cytospin preparations stained with TMEM119. Both, cytospin preparations and sections were subjected to computer-assisted density measurements. The density of microglial TMEM119-positive cortical profiles correlated with that of cytospin results and with the density of TMEM119-positive microglial profiles in the medullary layer. There was no statistically significant correlation between the density of medullary TMEM119-positive profiles and the cytospin data. Cortical microglial cells were primarily encountered in supragranular layers I, II, and IIIa and in infragranular layers V and VI, the region of U-fibers and in circumscribed foci or spread in a diffuse manner and high density over the white matter. We have evidence that cortical microglia directly migrate into CSF without using the glympathic pathway. Microglia in the medullary layer shows a strong affinity to the adventitia of deep vessels in the myelin layer. Selected rapidly fatal cases including myocardial infarcts and drowning let us conclude that microglia in cortex and myelin layer can react rapidly and its reaction and migration is subject to pre-existing external and internal factors. Cytospin preparations proved to be a simple tool to analyze and assess complex changes in the CNS after rapid fatal damage. There is no statistically significant correlation between cytospin and postmortem interval. Therefore, the quantitative analyses of postmortem cytospins obviously reflect the neuropathology of the complete central nervous system. Cytospins provide forensic pathologists a rather simple and easy to perform method for the global assessment of CNS affliction.
Background
CXCR4-directed positron emission tomography/computed tomography (PET/CT) has been used as a diagnostic tool in patients with solid tumors. We aimed to determine a potential correlation between tumor burden and radiotracer accumulation in normal organs.
Methods
Ninety patients with histologically proven solid cancers underwent CXCR4-targeted [\(^{68}\)Ga]Ga-PentixaFor PET/CT. Volumes of interest (VOIs) were placed in normal organs (heart, liver, spleen, bone marrow, and kidneys) and tumor lesions. Mean standardized uptake values (SUV\(_{mean}\)) for normal organs were determined. For CXCR4-positive tumor burden, maximum SUV (SUV\(_{max}\)), tumor volume (TV), and fractional tumor activity (FTA, defined as SUV\(_{mean}\) x TV), were calculated. We used a Spearman's rank correlation coefficient (ρ) to derive correlative indices between normal organ uptake and tumor burden.
Results
Median SUV\(_{mean}\) in unaffected organs was 5.2 for the spleen (range, 2.44 – 10.55), 3.27 for the kidneys (range, 1.52 – 17.4), followed by bone marrow (1.76, range, 0.84 – 3.98), heart (1.66, range, 0.88 – 2.89), and liver (1.28, range, 0.73 – 2.45). No significant correlation between SUV\(_{max}\) in tumor lesions (ρ ≤ 0.189, P ≥ 0.07), TV (ρ ≥ -0.204, P ≥ 0.06) or FTA (ρ ≥ -0.142, P ≥ 0.18) with the investigated organs was found.
Conclusions
In patients with solid tumors imaged with [\(^{68}\)Ga]Ga-PentixaFor PET/CT, no relevant tumor sink effect was noted. This observation may be of relevance for therapies with radioactive and non-radioactive CXCR4-directed drugs, as with increasing tumor burden, the dose to normal organs may remain unchanged.
Objectives
Mechanisms of wound healing are often impaired in patients with osteonecrosis of the jaw (ONJ). According to the guidelines for the treatment of this disease, early surgical intervention is indicated. However, surgery often faces complications such as wound healing disorders. The application of platelet-rich fibrin (PRF) after necrosectomy between bone and mucosa may constitute a promising approach to improve surgical results. An aspect that was not investigated until now is that PRF acts as a “bio-carrier” for antibiotics previously applied intravenously.
Materials and methods
We investigated the antimicrobial properties of PRF in 24 patients presenting ONJ undergoing systemic antibiosis with ampicillin/sulbactam. We measured the concentration of ampicillin/sulbactam in plasma and PRF and performed agar diffusion tests. Ampicillin/sulbactam was applied intravenously to the patient 10 minutes for blood sampling for PRF. No further incorporation of patients’ blood or PRF product with antibiotic drugs was obtained. Four healthy patients served as controls.
Results
Our results revealed that PRF is highly enriched with ampicillin/sulbactam that is released to the environment. The antibiotic concentration in PRF was comparable to the plasma concentration of ampicillin/sulbactam. The inhibition zone (IZ) of PRF was comparable to the standard ampicillin/sulbactam discs used in sensitivity testing.
Conclusions
The results of our study demonstrated that PRF is a reliable bio-carrier for systemic applied antibiotics and exhibits a large antimicrobial effect.
Clinical relevance
We describe a clinically useful feature of PRF as a bio-carrier for antibiotics. Especially when applied to poorly perfused tissues and bone such as in ONJ, the local release of antibiotics can reduce wound healing disorders like infections.
When interacting with sophisticated digital technologies, people often fall back on the same interaction scripts they apply to the communication with other humans—especially if the technology in question provides strong anthropomorphic cues (e.g., a human-like embodiment). Accordingly, research indicates that observers tend to interpret the body language of social robots in the same way as they would with another human being. Backed by initial evidence, we assumed that a humanoid robot will be considered as more dominant and competent, but also as more eerie and threatening once it strikes a so-called power pose. Moreover, we pursued the research question whether these effects might be accentuated by the robot’s body size. To this end, the current study presented 204 participants with pictures of the robot NAO in different poses (expansive vs. constrictive), while also manipulating its height (child-sized vs. adult-sized). Our results show that NAO’s posture indeed exerted strong effects on perceptions of dominance and competence. Conversely, participants’ threat and eeriness ratings remained statistically independent of the robot’s depicted body language. Further, we found that the machine’s size did not affect any of the measured interpersonal perceptions in a notable way. The study findings are discussed considering limitations and future research directions.
The relevance of user experience in safety–critical domains has been questioned and lacks empirical investigation. Based on previous studies examining user experience in consumer technology, we conducted an online survey on positive experiences with interactive technology in acute care. The participants of the study consisted of anaesthesiologists, nurses, and paramedics (N = 55) from three German cities. We report qualitative and quantitative data examining (1) the relevance and notion of user experience, (2) motivational orientations and psychological need satisfaction, and (3) potential correlates of hedonic, eudaimonic, and extrinsic motivations such as affect or meaning. Our findings reveal that eudaimonia was the most salient aspect in these experiences and that the relevance of psychological needs is differently ranked than in experiences with interactive consumer technology. We conclude that user experience should be considered in safety–critical domains, but research needs to develop further tools and methods to address the domain-specific requirements.
Pilot study of a new freely available computer-aided polyp detection system in clinical practice
(2022)
Purpose
Computer-aided polyp detection (CADe) systems for colonoscopy are already presented to increase adenoma detection rate (ADR) in randomized clinical trials. Those commercially available closed systems often do not allow for data collection and algorithm optimization, for example regarding the usage of different endoscopy processors. Here, we present the first clinical experiences of a, for research purposes publicly available, CADe system.
Methods
We developed an end-to-end data acquisition and polyp detection system named EndoMind. Examiners of four centers utilizing four different endoscopy processors used EndoMind during their clinical routine. Detected polyps, ADR, time to first detection of a polyp (TFD), and system usability were evaluated (NCT05006092).
Results
During 41 colonoscopies, EndoMind detected 29 of 29 adenomas in 66 of 66 polyps resulting in an ADR of 41.5%. Median TFD was 130 ms (95%-CI, 80–200 ms) while maintaining a median false positive rate of 2.2% (95%-CI, 1.7–2.8%). The four participating centers rated the system using the System Usability Scale with a median of 96.3 (95%-CI, 70–100).
Conclusion
EndoMind’s ability to acquire data, detect polyps in real-time, and high usability score indicate substantial practical value for research and clinical practice. Still, clinical benefit, measured by ADR, has to be determined in a prospective randomized controlled trial.
We give a collection of 16 examples which show that compositions \(g\) \(\circ\) \(f\) of well-behaved functions \(f\) and \(g\) can be badly behaved. Remarkably, in 10 of the 16 examples it suffices to take as outer function \(g\) simply a power-type or characteristic function. Such a collection of examples may serve as a source of exercises for a calculus course.
Hyper-IgM syndrome type 2 (HIGM2) is a B cell intrinsic primary immunodeficiency caused by mutations in AICDA encoding activation-induced cytidine deaminase (AID) which impair immunoglobulin class switch recombination (CSR) and somatic hypermutation (SHM). Whereas autosomal-recessive AID-deficiency (AR-AID) affects both CSR and SHM, the autosomal-dominant form (AD-AID) due to C-terminal heterozygous variants completely abolishes CSR but only partially affects SHM. AR-AID patients display enhanced germinal center (GC) reactions and autoimmune manifestations, which are not present in AD-AID, suggesting that SHM but not CSR regulates GC reactions and peripheral B cell tolerance. Herein, we describe two siblings with HIGM2 due to a novel homozygous AICDA mutation (c.428-1G > T) which disrupts the splice acceptor site of exon 4 and results in the sole expression of a truncated AID variant that lacks 10 highly conserved amino acids encoded by exon 4 (AID-ΔE4a). AID-ΔE4a patients suffered from defective CSR and enhanced GC reactions and were therefore indistinguishable from other AR-AID patients. However, the AID-ΔE4a variant only partially affected SHM as observed in AD-AID patients. In addition, AID-ΔE4a but not AD-AID patients revealed impaired targeting of mutational hotspot motives and distorted mutational patterns. Hence, qualitative defects in AID function and altered SHM rather than global decreased SHM activity may account for the disease phenotype in these patients.
FGF/FGFR signaling regulates embryogenesis, angiogenesis, tissue homeostasis and wound repair by modulating proliferation, differentiation, survival, migration and metabolism of target cells. Understandably, compelling evidence for deregulated FGF signaling in the development and progression of different types of tumors continue to emerge and FGFR inhibitors arise as potential targeted therapeutic agents, particularly in tumors harboring aberrant FGFR signaling. There is first evidence of a dual role of the FGF/FGFR system in both organogenesis and tumorigenesis, of which this review aims to provide an overview. FGF-1 and FGF-2 are expressed in the adrenal cortex and are the most powerful mitogens for adrenocortical cells. Physiologically, they are involved in development and maintenance of the adrenal gland and bind to a family of four tyrosine kinase receptors, among which FGFR1 and FGFR4 are the most strongly expressed in the adrenal cortex. The repeatedly proven overexpression of these two FGFRs also in adrenocortical cancer is thus likely a sign of their participation in proliferation and vascularization, though the exact downstream mechanisms are not yet elucidated. Thus, FGFRs potentially offer novel therapeutic targets also for adrenocortical carcinoma, a type of cancer resistant to conventional antimitotic agents.
Composite optimization problems, where the sum of a smooth and a merely lower semicontinuous function has to be minimized, are often tackled numerically by means of proximal gradient methods as soon as the lower semicontinuous part of the objective function is of simple enough structure. The available convergence theory associated with these methods (mostly) requires the derivative of the smooth part of the objective function to be (globally) Lipschitz continuous, and this might be a restrictive assumption in some practically relevant scenarios. In this paper, we readdress this classical topic and provide convergence results for the classical (monotone) proximal gradient method and one of its nonmonotone extensions which are applicable in the absence of (strong) Lipschitz assumptions. This is possible since, for the price of forgoing convergence rates, we omit the use of descent-type lemmas in our analysis.
Immunization of preterm infants: current evidence and future strategies to individualized approaches
(2022)
Preterm infants are at particularly high risk for infectious diseases. As this vulnerability extends beyond the neonatal period into childhood and adolescence, preterm infants benefit greatly from infection-preventive measures such as immunizations. However, there is an ongoing discussion about vaccine safety and efficacy due to preterm infants’ distinct immunological features. A significant proportion of infants remains un- or under-immunized when discharged from primary hospital stay. Educating health care professionals and parents, promoting maternal immunization and evaluating the potential of new vaccination tools are important means to reduce the overall burden from infectious diseases in preterm infants. In this narrative review, we summarize the current knowledge about vaccinations in premature infants. We discuss the specificities of early life immunity and memory function, including the role of polyreactive B cells, restricted B cell receptor diversity and heterologous immunity mediated by a cross-reactive T cell repertoire. Recently, mechanistic studies indicated that tissue-resident memory (Trm) cell populations including T cells, B cells and macrophages are already established in the fetus. Their role in human early life immunity, however, is not yet understood. Tissue-resident memory T cells, for example, are diminished in airway tissues in neonates as compared to older children or adults. Hence, the ability to make specific recall responses after secondary infectious stimulus is hampered, a phenomenon that is transcriptionally regulated by enhanced expression of T-bet. Furthermore, the microbiome establishment is a dominant factor to shape resident immunity at mucosal surfaces, but it is often disturbed in the context of preterm birth. The proposed function of Trm T cells to remember benign interactions with the microbiome might therefore be reduced which would contribute to an increased risk for sustained inflammation. An improved understanding of Trm interactions may determine novel targets of vaccination, e.g., modulation of T-bet responses and facilitate more individualized approaches to protect preterm babies in the future.
Task-based measures that capture neurocognitive processes can help bridge the gap between brain and behavior. To transfer tasks to clinical application, reliability is a crucial benchmark because it imposes an upper bound to potential correlations with other variables (e.g., symptom or brain data). However, the reliability of many task readouts is low. In this study, we scrutinized the retest reliability of a probabilistic reversal learning task (PRLT) that is frequently used to characterize cognitive flexibility in psychiatric populations. We analyzed data from N = 40 healthy subjects, who completed the PRLT twice. We focused on how individual metrics are derived, i.e., whether data were partially pooled across participants and whether priors were used to inform estimates. We compared the reliability of the resulting indices across sessions, as well as the internal consistency of a selection of indices. We found good to excellent reliability for behavioral indices as derived from mixed-effects models that included data from both sessions. The internal consistency was good to excellent. For indices derived from computational modeling, we found excellent reliability when using hierarchical estimation with empirical priors and including data from both sessions. Our results indicate that the PRLT is well equipped to measure individual differences in cognitive flexibility in reinforcement learning. However, this depends heavily on hierarchical modeling of the longitudinal data (whether sessions are modeled separately or jointly), on estimation methods, and on the combination of parameters included in computational models. We discuss implications for the applicability of PRLT indices in psychiatric research and as diagnostic tools.
Due to computational advances in the past decades, so-called intelligent systems can learn from increasingly complex data, analyze situations, and support users in their decision-making to address them. However, in practice, the complexity of these intelligent systems renders the user hardly able to comprehend the inherent decision logic of the underlying machine learning model. As a result, the adoption of this technology, especially for high-stake scenarios, is hampered. In this context, explainable artificial intelligence offers numerous starting points for making the inherent logic explainable to people. While research manifests the necessity for incorporating explainable artificial intelligence into intelligent systems, there is still a lack of knowledge about how to socio-technically design these systems to address acceptance barriers among different user groups. In response, we have derived and evaluated a nascent design theory for explainable intelligent systems based on a structured literature review, two qualitative expert studies, a real-world use case application, and quantitative research. Our design theory includes design requirements, design principles, and design features covering the topics of global explainability, local explainability, personalized interface design, as well as psychological/emotional factors.
Contemporary decision support systems are increasingly relying on artificial intelligence technology such as machine learning algorithms to form intelligent systems. These systems have human-like decision capacity for selected applications based on a decision rationale which cannot be looked-up conveniently and constitutes a black box. As a consequence, acceptance by end-users remains somewhat hesitant. While lacking transparency has been said to hinder trust and enforce aversion towards these systems, studies that connect user trust to transparency and subsequently acceptance are scarce. In response, our research is concerned with the development of a theoretical model that explains end-user acceptance of intelligent systems. We utilize the unified theory of acceptance and use in information technology as well as explanation theory and related theories on initial trust and user trust in information systems. The proposed model is tested in an industrial maintenance workplace scenario using maintenance experts as participants to represent the user group. Results show that acceptance is performance-driven at first sight. However, transparency plays an important indirect role in regulating trust and the perception of performance.
Purpose
To determine whether 24-h IOP monitoring can be a predictor for glaucoma progression and to analyze the inter-eye relationship of IOP, perfusion, and progression parameters.
Methods
We extracted data from manually drawn IOP curves with HIOP-Reader, a software suite we developed. The relationship between measured IOPs and mean ocular perfusion pressures (MOPP) to retinal nerve fiber layer (RNFL) thickness was analyzed. We determined the ROC curves for peak IOP (T\(_{max}\)), average IOP(T\(_{avg}\)), IOP variation (IOP\(_{var}\)), and historical IOP cut-off levels to detect glaucoma progression (rate of RNFL loss). Bivariate analysis was also conducted to check for various inter-eye relationships.
Results
Two hundred seventeen eyes were included. The average IOP was 14.8 ± 3.5 mmHg, with a 24-h variation of 5.2 ± 2.9 mmHg. A total of 52% of eyes with RNFL progression data showed disease progression. There was no significant difference in T\(_{max}\), T\(_{avg}\), and IOP\(_{var}\) between progressors and non-progressors (all p > 0.05). Except for T\(_{avg}\) and the temporal RNFL, there was no correlation between disease progression in any quadrant and T\(_{max}\), T\(_{avg}\), and IOP\(_{var}\). Twenty-four-hour and outpatient IOP variables had poor sensitivities and specificities in detecting disease progression. The correlation of inter-eye parameters was moderate; correlation with disease progression was weak.
Conclusion
In line with our previous study, IOP data obtained during a single visit (outpatient or inpatient monitoring) make for a poor diagnostic tool, no matter the method deployed. Glaucoma progression and perfusion pressure in left and right eyes correlated weakly to moderately with each other.
Key messages
What is known:
● Our prior study showed that manually obtained 24-hour inpatient IOP measurements in right eyes are poor predictors for glaucoma progression. The inter-eye relationship of 24-hour IOP parameters and disease progression on optical coherence tomography (OCT) has not been examined.
What we found:
● 24-hour IOP profiles of left eyes from the same study were a poor diagnostic tool to detect worsening glaucoma.
● Significant inter-eye correlations of various strengths were found for all tested parameters
The surgical treatment of parastomal hernias is considered complex and is known to be prone to complications. Traditionally, this condition was treated using relocation techniques or local suture repairs. Since then, several mesh-based techniques have been proposed and are nowadays used in minimally invasive surgery. Since the introduction of robot-assisted surgery to the field of abdominal wall surgery, several adaptations to these techniques have been made, which may significantly improve patient outcomes. In this contribution, we provide an overview of available techniques in robot-assisted parastomal hernia repair. Technical considerations and preliminary results of robot-assisted modified Sugarbaker repair, robot-assisted Pauli technique, and minimally invasive use of a funnel-shaped mesh in the treatment of parastomal hernias are presented. Furthermore, challenges in robot-assisted ileal conduit parastomal hernia repair are discussed. These techniques are illustrated by photographic and video material. Besides providing a comprehensive overview of robot-assisted parastomal hernia repair, this article focuses on the specific advantages of robot-assisted techniques in the treatment of this condition.
Purpose of Review
We review therapeutic approaches aimed at restoring function of the failing heart by targeting mitochondrial reactive oxygen species (ROS), ion handling, and substrate utilization for adenosine triphosphate (ATP) production.
Recent Findings
Mitochondria-targeted therapies have been tested in animal models of and humans with heart failure (HF). Cardiac benefits of sodium/glucose cotransporter 2 inhibitors might be partly explained by their effects on ion handling and metabolism of cardiac myocytes.
Summary
The large energy requirements of the heart are met by oxidative phosphorylation in mitochondria, which is tightly regulated by the turnover of ATP that fuels cardiac contraction and relaxation. In heart failure (HF), this mechano-energetic coupling is disrupted, leading to bioenergetic mismatch and production of ROS that drive the progression of cardiac dysfunction. Furthermore, HF is accompanied by changes in substrate uptake and oxidation that are considered detrimental for mitochondrial oxidative metabolism and negatively affect cardiac efficiency. Mitochondria lie at the crossroads of metabolic and energetic dysfunction in HF and represent ideal therapeutic targets.
Severe and prolonged liver damage in pityriasis rubra pilaris treated with acitretin: a case report
(2022)
Acitretin is a systemic retinoid that is used in dermatology for treatment of various inflammatory and especially hyperkeratotic diseases. Elevation of liver enzymes may occur occasionally but normally resolves spontaneously, at the latest after termination of acitretin. However, it can very rarely develop into a life-threatening adverse event including drug-induced liver injury (DILI). A 45-year-old man with classical pityriasis rubra pilaris, a frequently severe, inflammatory skin disease, was started on acitretin. After a seemingly harmless elevation of transaminases, a few weeks after initiation of acitretin, the patient experienced a dramatic course of liver injury with hepatic jaundice though acitretin was stopped immediately. Eventually, laboratory values recovered upon high-dose oral prednisolone therapy. Prescribing physicians should keep in mind that acitretin might induce severe liver injury. Even after termination of acitretin laboratory values should be monitored for a while in order to recognize symptomless but harmful drug-induced liver injury in time.
Purpose
A successful focused surgical approach in primary hyperparathyroidism (pHPT) relies on accurate preoperative localization of the parathyroid adenoma (PA). Most often, ultrasound is followed by [\(^{99m}\)Tc]-sestamibi scintigraphy, but the value of this approach is disputed. Here, we evaluated the diagnostic approach in patients with surgically treated pHPT in our center with the aim to further refine preoperative diagnostic procedures.
Methods
A single-center retrospective analysis of patients with pHPT from 01/2005 to 08/2021 was carried out followed by evaluation of the preoperative imaging modalities to localize PA. The localization of the PA had to be confirmed intraoperatively by the fresh frozen section and significant dropping of the intraoperative parathyroid hormone (PTH) levels.
Results
From 658 patients diagnosed with pHPT, 30 patients were excluded from the analysis because of surgery for recurrent or persistent disease. Median age of patients was 58.0 (13–93) years and 71% were female. Neck ultrasound was carried out in 91.7% and localized a PA in 76.6%. In 23.4% (135/576) of the patients, preoperative neck ultrasound did not detect a PA. In this group, [\(^{99m}\)Tc]-sestamibi correctly identified PA in only 25.4% of patients. In contrast, in the same cohort, the use of [\(^{11}\)C]-methionine or [\(^{11}\)C]-choline PET resulted in the correct identification of PA in 79.4% of patients (OR 13.23; 95% CI 5.24–33.56).
Conclusion
[\(^{11}\)C]-Methionine or [\(^{11}\)C]-choline PET/CT are superior second-line imaging methods to select patients for a focused surgical approach when previous ultrasound failed to identify PA.
Background
An intragastric balloon is used to cause weight loss in super-obese patients (BMI > 60 kg/m\(^2\)) prior to bariatric surgery. Whether weight loss from intragastric balloon influences that from bariatric surgery is poorly studied.
Methods
In this retrospective, single-center study, the effects of intragastric balloon in 26 patients (BMI 69.26 ± 6.81) on weight loss after bariatric surgery (primary endpoint), postoperative complications within 30 days, hospital readmission, operation time, and MTL30 (secondary endpoints) were evaluated. Fifty-two matched-pair patients without intragastric balloon prior to bariatric surgery were used as controls.
Results
Intragastric balloon resulted in a weight loss of 17.3 ± 14.1 kg (BMI 5.75 ± 4.66 kg/m\(^2\)) with a nadir after 5 months. Surgical and postoperative outcomes including complications were comparable between both groups. Total weight loss was similar in both groups (29.0% vs. 32.2%, p = 0.362). Direct postoperative weight loss was more pronounced in the control group compared to the gastric balloon group (29.16 ± 7.53% vs 23.78 ± 9.89% after 1 year, p < 0.05 and 32.13 ± 10.5% vs 22.21 ± 10.9% after 2 years, p < 0.05), who experienced an earlier nadir and started to regain weight during the follow-up.
Conclusion
A multi-stage therapeutic approach with gastric balloon prior to bariatric surgery in super-obese patients may be effective to facilitate safe surgery. However, with the gastric balloon, pre-treated patients experienced an attenuated postoperative weight loss with an earlier nadir and earlier body weight regain. This should be considered when choosing the appropriate therapeutic regime and managing patients’ expectations.
The July 2021 heavy rainfall episode in parts of Western Europe caused devastating floods, specifically in Germany. This study examines circulation types (CTs) linked to extreme precipitation in Germany. It was investigated if the classified CTs can highlight the anomaly in synoptic patterns that contributed to the unusual July 2021 heavy rainfall in Germany. The North Atlantic Oscillation was found to be the major climatic mode related to the seasonal and inter-annual variations of most of the classified CTs. On average, wet (dry) conditions in large parts of Germany can be linked to westerly (northerly) moisture fluxes. During spring and summer seasons, the mid-latitude cyclone when located over the North Sea disrupts onshore moisture transport from the North Atlantic Ocean by westerlies driven by the North Atlantic subtropical anticyclone. The CT found to have the highest probability of being associated with above-average rainfall in large part of Germany features (i) enhancement and northward track of the cyclonic system over the Mediterranean; (ii) northward track of the North Atlantic anticyclone, further displacing poleward, the mid-latitude cyclone over the North Sea, enabling band of westerly moisture fluxes to penetrate Germany; (iii) cyclonic system over the Baltic Sea coupled with northeast fluxes of moisture to Germany; (iv) and unstable atmospheric conditions over Germany. In 2021, a spike was detected in the amplitude and frequency of occurrence of the aforementioned wet CT suggesting that in addition to the nearly stationary cut-off low over central Europe, during the July flood episode, anomalies in the CT contributed to the heavy rainfall event.
New U–Pb age and Hf isotope data obtained on detrital zircon grains from Au- and U-bearing Archaean quartz-pebble conglomerates in the Singhbhum Craton, eastern India, specifically the Upper Iron Ore Group in the Badampahar Greenstone Belt and the Phuljhari Formation below the Dhanjori Group provide insights into the zircon provenance and maximum age of sediment deposition. The most concordant, least disturbed \(^{207}\)Pb/\(^{206}\)Pb ages cover the entire range of known magmatic and higher grade metamorphic events in the craton from 3.48 to 3.06 Ga and show a broad maximum between 3.38 and 3.18 Ga. This overlap is also mimicked by Lu–Hf isotope analyses, which returned a wide range in \(_{εHf}\)(t) values from + 6 to − 5, in agreement with the range known from zircon grains in igneous and metamorphic rocks in the Singhbhum Craton. A smaller but distinct age peak centred at 3.06 Ga corresponds to the age of the last major magmatic intrusive event, the emplacement of the Mayurbhanj Granite and associated gabbro, picrite and anorthosite. Thus, these intrusive rocks must form a basement rather than being intrusive into the studied conglomerates as previously interpreted. The corresponding detrital zircon grains all have a subchondritic Hf isotopic composition. The youngest reliable zircon ages of 3.03 Ga in the case of the basal Upper Iron Ore Group in the east of the craton and 3.00 Ga for the Phuljhari Formation set an upper limit on the age of conglomerate sedimentation. Previously published detrital zircon age data from similarly Au-bearing conglomerates in the Mahagiri Quartzite in the Upper Iron Ore Group in the south of the craton gave a somewhat younger maximum age of sedimentation of 2.91 Ga. There, the lower limit on sedimentation is given by an intrusive relationship with a c. 2.8 Ga granite. The time window thus defined for conglomerate deposition on the Singhbhum Craton is almost identical to the age span established for the, in places, Au- and U-rich conglomerates in the Kaapvaal Craton of South Africa: the 2.98–2.78 Ga Dominion Group and Witwatersrand Supergroup in South Africa. Since the recognition of first major concentration of gold on Earth’s surface by microbial activity having taken place at around 2.9 Ga, independent of the nature of the hinterland, the above similarity in age substantially increases the potential for discovering Witwatersrand-type gold and/or uranium deposits on the Singhbhum Craton. Further age constraints are needed there, however, to distinguish between supposedly less fertile (with respect to Au) > 2.9 Ga and more fertile < 2.9 Ga successions.
The effects of drought on tree mortality at forest stands are not completely understood. For assessing their water supply, knowledge of the small-scale distribution of soil moisture as well as its temporal changes is a key issue in an era of climate change. However, traditional methods like taking soil samples or installing data loggers solely collect parameters of a single point or of a small soil volume. Electrical resistivity tomography (ERT) is a suitable method for monitoring soil moisture changes and has rarely been used in forests. This method was applied at two forest sites in Bavaria, Germany to obtain high-resolution data of temporal soil moisture variations. Geoelectrical measurements (2D and 3D) were conducted at both sites over several years (2015–2018/2020) and compared with soil moisture data (matric potential or volumetric water content) for the monitoring plots. The greatest variations in resistivity values that highly correlate with soil moisture data were found in the main rooting zone. Using the ERT data, temporal trends could be tracked in several dimensions, such as the interannual increase in the depth of influence from drought events and their duration, as well as rising resistivity values going along with decreasing soil moisture. The results reveal that resistivity changes are a good proxy for seasonal and interannual soil moisture variations. Therefore, 2D- and 3D-ERT are recommended as comparatively non-laborious methods for small-spatial scale monitoring of soil moisture changes in the main rooting zone and the underlying subsurface of forested sites. Higher spatial and temporal resolution allows a better understanding of the water supply for trees, especially in times of drought.
Background
Remote monitoring of patients with New York Heart Association (NYHA) functional class III heart failure (HF) using daily transmission of pulmonary artery (PA) pressure values has shown a reduction in HF-related hospitalizations and improved quality of life in patients.
Objectives
PASSPORT-HF is a prospective, randomized, open, multicenter trial evaluating the effects of a hemodynamic-guided, HF nurse-led care approach using the CardioMEMS™ HF-System on clinical end points.
Methods and results
The PASSPORT-HF trial has been commissioned by the German Federal Joint Committee (G-BA) to ascertain the efficacy of PA pressure-guided remote care in the German health-care system. PASSPORT-HF includes adult HF patients in NYHA functional class III, who experienced an HF-related hospitalization within the last 12 months. Patients with reduced ejection fraction must be on stable guideline-directed pharmacotherapy. Patients will be randomized centrally 1:1 to implantation of a CardioMEMS™ sensor or control. All patients will receive post-discharge support facilitated by trained HF nurses providing structured telephone-based care. The trial will enroll 554 patients at about 50 study sites. The primary end point is a composite of the number of unplanned HF-related rehospitalizations or all-cause death after 12 months of follow-up, and all events will be adjudicated centrally. Secondary end points include device/system-related complications, components of the primary end point, days alive and out of hospital, disease-specific and generic health-related quality of life including their sub-scales, and laboratory parameters of organ damage and disease progression.
Conclusions
PASSPORT-HF will define the efficacy of implementing hemodynamic monitoring as a novel disease management tool in routine outpatient care.
Trial registration
ClinicalTrials.gov; NCT04398654, 13-MAY-2020.
A fuzzy classification scheme that results in physically interpretable meteorological patterns associated with rainfall generation is applied to classify homogeneous regions of boreal summer rainfall anomalies in Germany. Four leading homogeneous regions are classified, representing the western, southeastern, eastern, and northern/northwestern parts of Germany with some overlap in the central parts of Germany. Variations of the sea level pressure gradient across Europe, e.g., between the continental and maritime regions, is the major phenomenon that triggers the time development of the rainfall regions by modulating wind patterns and moisture advection. Two regional climate models (REMO and CCLM4) were used to investigate the capability of climate models to reproduce the observed summer rainfall regions. Both regional climate models (RCMs) were once driven by the ERA-Interim reanalysis and once by the MPI-ESM general circulation model (GCM). Overall, the RCMs exhibit good performance in terms of the regionalization of summer rainfall in Germany; though the goodness-of-match with the rainfall regions/patterns from observational data is low in some cases and the REMO model driven by MPI-ESM fails to reproduce the western homogeneous rainfall region. Under future climate change, virtually the same leading modes of summer rainfall occur, suggesting that the basic synoptic processes associated with the regional patterns remain the same over Germany. We have also assessed the added value of bias-correcting the MPI-ESM driven RCMs using a simple linear scaling approach. The bias correction does not significantly alter the identification of homogeneous rainfall regions and, hence, does not improve their goodness-of-match compared to the observed patterns, except for the one case where the original RCM output completely fails to reproduce the observed pattern. While the linear scaling method improves the basic statistics of precipitation, it does not improve the simulated meteorological patterns represented by the precipitation regimes.
Performance of a regional climate model with interactive vegetation (REMO-iMOVE) over Central Asia
(2022)
The current study evaluates the regional climate model REMO (v2015) and its new version REMO-iMOVE, including interactive vegetation and plant functional types (PFTs), over two Central Asian domains for the period of 2000–2015 at two different horizontal resolutions (0.44° and 0.11°). Various statistical metrices along with mean bias patterns for precipitation, temperature, and leaf area index have been used for the model evaluation. A better representation of the spatial pattern of precipitation is found at 0.11° resolution over most of Central Asia. Regarding the mean temperature, both model versions show a high level of agreement with the validation data, especially at the higher resolution. This also reduces the biases in maximum and minimum temperature. Generally, REMO-iMOVE shows an improvement regarding the temperature bias but produces a larger precipitation bias compared to the REMO conventional version with interannually static vegetation. Since the coupled version is capable to simulate the mean climate of Central Asia like its parent version, both can be used for impact studies and future projections. However, regarding the new vegetation scheme and its spatiotemporal representation exemplified by the leaf area index, REMO-iMOVE shows a clear advantage over REMO. This better simulation is caused by the implementation of more realistic and interactive vegetation and related atmospheric processes which consequently add value to the regional climate model.
Purpose
Surgery is a standard therapy for tympanojugular paragangliomas (TJP). Maintaining the quality of life (QoL) requires functional preservation. The flexible CO\(_2\) laser allows contact-free tumor removal. This retrospective study compares the postoperative functional outcomes of TJP surgery with and without the flexible CO\(_2\) laser.
Methods
Between 2005 and 2019, 51 patients with TJP were surgically treated at a tertiary hospital. Until 2012, 17 patients received conventional surgery. Thereafter, the flexible laser was used in 34 patients. Tumor extend, pre- and postoperative cranial nerve function, and complications were compared between the groups.
Results
The cohort consisted of 33 class A and B tumors and 18 class C and D tumors. Preoperative embolization was performed in 17 cases. Class C/D TJP were usually removed via an infratemporal fossa type A approach. Gross total tumor removal was achieved in 14/18 class C/D tumors. 3/51 patients suffered from long-term partial or complete facial palsy. No differences in post-therapeutic cranial nerve function or complications were noted between the conventional and laser group. One recurrence was observed after complete tumor resection.
Conclusion
The flexible CO\(_2\) laser was shown to be a safe and effective alternative to conventional bipolar cauterization, which is appreciated by the surgeon in these highly vascularized tumors. Both techniques allowed a high tumor control rate and good long-term results also from a functional point of view.
Learning is a central component of human life and essential for personal development. Therefore, utilizing new technologies in the learning context and exploring their combined potential are considered essential to support self-directed learning in a digital age. A learning environment can be expanded by various technical and content-related aspects. Gamification in the form of elements from video games offers a potential concept to support the learning process. This can be supplemented by technology-supported learning. While the use of tablets is already widespread in the learning context, the integration of a social robot can provide new perspectives on the learning process. However, simply adding new technologies such as social robots or gamification to existing systems may not automatically result in a better learning environment. In the present study, game elements as well as a social robot were integrated separately and conjointly into a learning environment for basic Spanish skills, with a follow-up on retained knowledge. This allowed us to investigate the respective and combined effects of both expansions on motivation, engagement and learning effect. This approach should provide insights into the integration of both additions in an adult learning context. We found that the additions of game elements and the robot did not significantly improve learning, engagement or motivation. Based on these results and a literature review, we outline relevant factors for meaningful integration of gamification and social robots in learning environments in adult learning.
Xylem embolism resistance has been identified as a key trait with a causal relation to drought-induced tree mortality, but not much is known about its intra-specific trait variability (ITV) in dependence on environmental variation. We measured xylem safety and efficiency in 300 European beech (Fagus sylvatica L.) trees across 30 sites in Central Europe, covering a precipitation reduction from 886 to 522 mm year−1. A broad range of variables that might affect embolism resistance in mature trees, including climatic and soil water availability, competition, and branch age, were examined. The average P50 value varied by up to 1 MPa between sites. Neither climatic aridity nor structural variables had a significant influence on P50. However, P50 was less negative for trees with a higher soil water storage capacity, and positively related to branch age, while specific conductivity (Ks) was not significantly associated with either of these variables. The greatest part of the ITV for xylem safety and efficiency was attributed to random variability within populations. We conclude that the influence of site water availability on P50 and Ks is low in European beech, and that the high degree of within-population variability for P50, partly due to variation in branch age, hampers the identification of a clear environmental signal.
“I tried to control my emotions”: nursing home care workers’ experiences of emotional labor in China
(2022)
Despite dramatic expansions in the Chinese nursing home sector in meeting the increasing care needs of a rapidly aging population, direct care work in China remains largely devalued and socially unrecognized. Consequently, scant attention has been given to the caregiving experiences of direct care workers (DCWs) in Chinese nursing homes. In particular, given the relational nature of care work, there is little knowledge as to how Chinese DCWs manage emotions and inner feelings through their emotional labor. This article examines the emotional labor of Chinese DCWs through ethnographic data collected with 20 DCWs in one nursing home located in an urban setting in central China. Data were analyzed using conventional content analysis and constant comparison. Participants’ accounts of sustaining a caring self, preserving professional identity, and hoping for reciprocity revealed implicit meanings about the often-conflicting nature of emotional labor and the nonreciprocal elements of care work under constrained working conditions. Importantly, the moral-cultural notion of bao (报 norm of reciprocity) was found to be central among DCWs in navigating strained resources and suggested their agency in meaning-construction. However, their constructed moral buffers may be insufficient if emotional labor continues to be made invisible by care organizations.
Background
Endoscopic vacuum therapy (EVT) is an effective treatment option for leakage of the upper gastrointestinal (UGI) tract. The aim of this study was to evaluate the clinical impact of quality improvements in EVT management on patients’ outcome.
Methods
All patients treated by EVT at our center during 2012–2021 were divided into two consecutive and equal-sized cohorts (period 1 vs. period 2). Over time several quality improvement strategies were implemented including the earlier diagnosis and EVT treatment and technical optimization of endoscopy. The primary endpoint was defined as the composite score MTL30 (mortality, transfer, length-of-stay > 30 days). Secondary endpoints included EVT efficacy, complications, in-hospital mortality, length-of-stay (LOS) and nutrition status at discharge.
Results
A total of 156 patients were analyzed. During the latter period the primary endpoint MTL30 decreased from 60.8 to 39.0% (P = .006). EVT efficacy increased from 80 to 91% (P = .049). Further, the need for additional procedures for leakage management decreased from 49.9 to 29.9% (P = .013) and reoperations became less frequent (38.0% vs.15.6%; P = .001). The duration of leakage therapy and LOS were shortened from 25 to 14 days (P = .003) and 38 days to 25 days (P = .006), respectively. Morbidity (as determined by the comprehensive complication index) decreased from 54.6 to 46.5 (P = .034). More patients could be discharged on oral nutrition (70.9% vs. 84.4%, P = .043).
Conclusions
Our experience confirms the efficacy of EVT for the successful management of UGI leakage. Our quality improvement analysis demonstrates significant changes in EVT management resulting in accelerated recovery, fewer complications and improved functional outcome.
Purpose
In selected cases of severe Cushing’s syndrome due to uncontrolled ACTH secretion, bilateral adrenalectomy appears unavoidable. Compared with unilateral adrenalectomy (for adrenal Cushing’s syndrome), bilateral adrenalectomy has a perceived higher perioperative morbidity. The aim of the current study was to compare both interventions in endogenous Cushing’s syndrome regarding postoperative outcomes.
Methods
We report a single-center, retrospective cohort study comparing patients with hypercortisolism undergoing bilateral vs. unilateral adrenalectomy during 2008–2021. Patients with adrenal Cushing’s syndrome due to adenoma were compared with patients with ACTH-dependent Cushing’s syndrome (Cushing’s disease and ectopic ACTH production) focusing on postoperative morbidity and mortality as well as long-term survival.
Results
Of 83 patients with adrenalectomy for hypercortisolism (65.1% female, median age 53 years), the indication for adrenalectomy was due to adrenal Cushing’s syndrome in 60 patients (72.2%; 59 unilateral and one bilateral), and due to hypercortisolism caused by Cushing’s disease (n = 16) or non-pituitary uncontrolled ACTH secretion of unknown origin (n = 7) (27.7% of all adrenalectomies). Compared with unilateral adrenalectomy (n = 59), patients with bilateral adrenalectomy (n = 24) had a higher rate of severe complications (0% vs. 33%; p < 0.001) and delayed recovery (median: 10.2% vs. 79.2%; p < 0.001). Using the MTL30 marker, patients with bilateral adrenalectomy fared worse than patients after unilateral surgery (MTL30 positive: 7.2% vs. 25.0% p < 0.001). Postoperative mortality was increased in patients with bilateral adrenalectomy (0% vs. 8.3%; p = 0.081).
Conclusion
While unilateral adrenalectomy for adrenal Cushing’s syndrome represents a safe and definitive therapeutic option, bilateral adrenalectomy to control ACTH-dependent extra-adrenal Cushing’s syndrome or Cushing’s disease is a more complicated intervention with a mortality of nearly 10%.
Introduction
Low-grade appendiceal mucinous neoplasms (LAMN) are semi-malignant tumors of the appendix which are incidentally found in up to 1% of appendectomy specimen. To this day, no valid descriptive analysis on LAMN is available for the German population.
Methods
Data of LAMN (ICD-10: D37.3) were collected from the population-based cancer registries in Germany, provided by the German Center for Cancer Registry Data (Zentrum für Krebsregisterdaten—ZfKD). Data was anonymized and included gender, age at diagnosis, tumor staging according to the TNM-classification, state of residence, information on the performed therapy, and survival data.
Results
A total of 612 cases were reported to the ZfKD between 2011 and 2018. A total of 63.07% were female and 36.93% were male. Great inhomogeneity in reporting cases was seen in the federal states of Germany including the fact that some federal states did not report any cases at all. Age distribution showed a mean age of 62.03 years (SD 16.15) at diagnosis. However, data on tumor stage was only available in 24.86% of cases (n = 152). A total of 49.34% of these patients presented with a T4-stage. Likewise, information regarding performed therapy was available in the minority of patients: 269 patients received surgery, 22 did not and for 312 cases no information was available. Twenty-four patients received chemotherapy, 188 did not, and for 400 cases, no information was available. Overall 5-year survival was estimated at 79.52%. Patients below the age of 55 years at time of diagnosis had a significantly higher 5-year survival rate compared to patients above the age of 55 years (85.77% vs. 73.27%).
Discussion
In this study, we observed an incidence of LAMN in 0.13% of all appendectomy specimen in 2018. It seems likely that not all cases were reported to the ZfKD; therefore, case numbers may be considered underestimated. Age and gender distribution goes in line with international studies with females being predominantly affected. Especially regarding tumor stage and therapy in depth information cannot be provided through the ZfKD-database. This data analysis emphasizes the need for further studies and the need for setting up a specialized registry for this unique tumor entity to develop guidelines for the appropriate treatment and follow-up.
Background
Pancreatic adenocarcinoma (PDAC) patients with preoperative carbohydrate antigen 19-9 (CA19-9) serum levels higher than 500 U/ml are classified as biologically borderline resectable (BR-B). To date, the impact of cholestasis on preoperative CA19-9 serum levels in these patients has remained unquantified.
Methods
Data on 3079 oncologic pancreatic resections due to PDAC that were prospectively acquired by the German Study, Documentation and Quality (StuDoQ) registry were analyzed in relation to preoperative CA19-9 and bilirubin serum values. Preoperative CA19-9 values were adjusted according to the results of a multivariable linear regression analysis of pathologic parameters, bilirubin, and CA19-9 values.
Results
Of 1703 PDAC patients with tumor located in the pancreatic head, 420 (24.5 %) presented with a preoperative CA19-9 level higher than 500 U/ml. Although receiver operating characteristics (ROC) analysis failed to determine exact CA19-9 cut-off values for prognostic indicators (R and N status), the T, N, and G status; the UICC stage; and the number of simultaneous vein resections increased with the level of preoperative CA19-9, independently of concurrent cholestasis. After adjustment of preoperative CA19-9 values, 18.5 % of patients initially staged as BR-B showed CA19-9 values below 500 U/ml. However, the postoperative pathologic results for these patients did not change compared with the patients who had CA19-9 levels higher than 500 U/ml after bilirubin adjustment.
Conclusions
In this multicenter dataset of PDAC patients, elevation of preoperative CA19-9 correlated with well-defined prognostic pathologic parameters. Bilirubin adjustment of CA19-9 is feasible but does not affect the prognostic value of CA19-9 in jaundiced patients.
Purpose
Anaemia is common in patients presenting with aneurysmal subarachnoid (aSAH) and intracerebral haemorrhage (ICH). In surgical patients, anaemia was identified as an idenpendent risk factor for postoperative mortality, prolonged hospital length of stay (LOS) and increased risk of red blood cell (RBC) transfusion. This multicentre cohort observation study describes the incidence and effects of preoperative anaemia in this critical patient collective for a 10-year period.
Methods
This multicentre observational study included adult in-hospital surgical patients diagnosed with aSAH or ICH of 21 German hospitals (discharged from 1 January 2010 to 30 September 2020). Descriptive, univariate and multivariate analyses were performed to investigate the incidence and association of preoperative anaemia with RBC transfusion, in-hospital mortality and postoperative complications in patients with aSAH and ICH.
Results
A total of n = 9081 patients were analysed (aSAH n = 5008; ICH n = 4073). Preoperative anaemia was present at 28.3% in aSAH and 40.9% in ICH. RBC transfusion rates were 29.9% in aSAH and 29.3% in ICH. Multivariate analysis revealed that preoperative anaemia is associated with a higher risk for RBC transfusion (OR = 3.25 in aSAH, OR = 4.16 in ICH, p < 0.001), for in-hospital mortality (OR = 1.48 in aSAH, OR = 1.53 in ICH, p < 0.001) and for several postoperative complications.
Conclusions
Preoperative anaemia is associated with increased RBC transfusion rates, in-hospital mortality and postoperative complications in patients with aSAH and ICH.
PURPOSE
The threat of national and international terrorism remains high. Preparation is the key requirement for the resilience of hospitals and out-of-hospital rescue forces. The scientific evidence for defining medical and tactical strategies often feeds on the analysis of real incidents and the lessons learned derived from them. This systematic review of the literature aims to identify and systematically report lessons learned from terrorist attacks since 2001.
METHODS
PubMed was used as a database using predefined search strategies and eligibility criteria. All countries that are part of the Organization for Economic Cooperation and Development (OECD) were included. The time frame was set between 2001 and 2018.
RESULTS
Finally 68 articles were included in the review. From these, 616 lessons learned were extracted and summarized into 15 categories. The data shows that despite the difference in attacks, countries, and casualties involved, many of the lessons learned are similar. We also found that the pattern of lessons learned is repeated continuously over the time period studied.
CONCLUSIONS
The lessons from terrorist attacks since 2001 follow a certain pattern and remained constant over time. Therefore, it seems to be more accurate to talk about lessons identified rather than lessons learned. To save as many victims as possible, protect rescue forces from harm, and to prepare hospitals at the best possible level it is important to implement the lessons identified in training and preparation.
With the increasing adaptability and complexity of advisory artificial intelligence (AI)-based agents, the topics of explainable AI and human-centered AI are moving close together. Variations in the explanation itself have been widely studied, with some contradictory results. These could be due to users’ individual differences, which have rarely been systematically studied regarding their inhibiting or enabling effect on the fulfillment of explanation objectives (such as trust, understanding, or workload). This paper aims to shed light on the significance of human dimensions (gender, age, trust disposition, need for cognition, affinity for technology, self-efficacy, attitudes, and mind attribution) as well as their interplay with different explanation modes (no, simple, or complex explanation). Participants played the game Deal or No Deal while interacting with an AI-based agent. The agent gave advice to the participants on whether they should accept or reject the deals offered to them. As expected, giving an explanation had a positive influence on the explanation objectives. However, the users’ individual characteristics particularly reinforced the fulfillment of the objectives. The strongest predictor of objective fulfillment was the degree of attribution of human characteristics. The more human characteristics were attributed, the more trust was placed in the agent, advice was more likely to be accepted and understood, and important needs were satisfied during the interaction. Thus, the current work contributes to a better understanding of the design of explanations of an AI-based agent system that takes into account individual characteristics and meets the demand for both explainable and human-centered agent systems.
The Moroccan locust has been considered one of the most dangerous agricultural pests in the Mediterranean region. The economic importance of its outbreaks diminished during the second half of the 20th century due to a high degree of agricultural industrialization and other human-caused transformations of its habitat. Nevertheless, in Sardinia (Italy) from 2019 on, a growing invasion of this locust species is ongoing, being the worst in over three decades. Locust swarms destroyed crops and pasture lands of approximately 60,000 ha in 2022. Drought, in combination with increasing uncultivated land, contributed to forming the perfect conditions for a Moroccan locust population upsurge. The specific aim of this paper is the quantification of land cover land use (LCLU) influence with regard to the recent locust outbreak in Sardinia using remote sensing data. In particular, the role of untilled, fallow, or abandoned land in the locust population upsurge is the focus of this case study. To address this objective, LCLU was derived from Sentinel-2A/B Multispectral Instrument (MSI) data between 2017 and 2021 using time-series composites and a random forest (RF) classification model. Coordinates of infested locations, altitude, and locust development stages were collected during field observation campaigns between March and July 2022 and used in this study to assess actual and previous land cover situation of these locations. Findings show that 43% of detected locust locations were found on untilled, fallow, or uncultivated land and another 23% within a radius of 100 m to such areas. Furthermore, oviposition and breeding sites are mostly found in sparse vegetation (97%). This study demonstrates that up-to-date remote sensing data and target-oriented analyses can provide valuable information to contribute to early warning systems and decision support and thus to minimize the risk concerning this agricultural pest. This is of particular interest for all agricultural pests that are strictly related to changing human activities within transformed habitats.
A novel method for detecting and delineating coppice trees in UAV images to monitor tree decline
(2022)
Monitoring tree decline in arid and semi-arid zones requires methods that can provide up-to-date and accurate information on the health status of the trees at single-tree and sample plot levels. Unmanned Aerial Vehicles (UAVs) are considered as cost-effective and efficient tools to study tree structure and health at small scale, on which detecting and delineating tree crowns is the first step to extracting varied subsequent information. However, one of the major challenges in broadleaved tree cover is still detecting and delineating tree crowns in images. The frequent dominance of coppice structure in degraded semi-arid vegetation exacerbates this problem. Here, we present a new method based on edge detection for delineating tree crowns based on the features of oak trees in semi-arid coppice structures. The decline severity in individual stands can be analyzed by extracting relevant information such as texture from the crown area. Although the method presented in this study is not fully automated, it returned high performances including an F-score = 0.91. Associating the texture indices calculated in the canopy area with the phenotypic decline index suggested higher correlations of the GLCM texture indices with tree decline at the tree level and hence a high potential to be used for subsequent remote-sensing-assisted tree decline studies.
High rates of land conversion due to urbanization are causing fragmented and dispersed spatial patterns in the wildland-urban interface (WUI) worldwide. The occurrence of anthropogenic fires in the WUI represents an important environmental and social issue, threatening not only vegetated areas but also periurban inhabitants, as is the case in many Latin American cities. However, research has not focused on the dynamics of the local climate in the WUI. This study analyzes whether wildfires contribute to the increase in land surface temperature (LST) in the WUI of the metropolitan area of the city of Guanajuato (MACG), a semi-arid Mexican city. We estimated the pre- and post-fire LST for 2018–2021. Spatial clusters of high LST were detected using hot spot analysis and examined using ANOVA and Tukey’s post-hoc statistical tests to assess whether LST is related to the spatial distribution of wildfires during our study period. Our results indicate that the areas where the wildfires occurred, and their surroundings, show higher LST. This has negative implications for the local ecosystem and human population, which lacks adequate infrastructure and services to cope with the effects of rising temperatures. This is the first study assessing the increase in LST caused by wildfires in a WUI zone in Mexico.
Background: Phenprocoumon has been used as an oral anticoagulant in patients with thromboembolic disease for more than 40 years. So far its pharmacokinetics have not been analyzed in emergency situations. Methods: Phenprocoumon-treated patients with major bleeding or urgent surgery were included in a prospective, observational registry. Phenprocoumon drug concentrations were analyzed in samples, collected as part of routine care using ultraperformance liquid chromatography tandem mass spectrometry. Moreover, anticoagulant intensity and drug half-life (t1/2) were calculated. Results: 115 patients were included. Phenprocoumon levels declined over time with a half-life of 5.27 and 5.29 days in patients with major bleedings (n = 82) and with urgent surgery (n = 33). Baseline phenprocoumon levels were 2.2 times higher in the bleeding group compared to the surgery group (1.92 vs. 0.87 ng/mL, p < 0.0001). International normalized ratio (INR) values decreased rapidly during the first 24 h. In 27.6% of patients a rebound of INR (recurrent increase > 1.5) was observed which was associated with significantly increased bleeding rates (22% vs. 4.2% in patients with or without INR rebound, p = 0.012). Conclusions: In emergency situations, the long half-life of phenprocoumon may cause INR rebound and associated recurrent bleedings. Optimal management may need to include repeated vitamin K supplementation over days.
Ruxolitinib (RUX) is approved for the treatment of steroid-refractory acute and chronic graft versus host disease (GvHD). It is predominantly metabolized via cytochrome P450 (CYP) 3A4. As patients with GvHD have an increased risk of invasive fungal infections, RUX is frequently combined with posaconazole (POS), a strong CYP3A4 inhibitor. Knowledge of RUX exposure under concomitant POS treatment is scarce and recommendations on dose modifications are inconsistent. A physiologically based pharmacokinetic (PBPK) model was developed to investigate the drug–drug interaction (DDI) between POS and RUX. The predicted RUX exposure was compared to observed concentrations in patients with GvHD in the clinical routine. PBPK models for RUX and POS were independently set up using PK-Sim\(^®\) Version 11. Plasma concentration-time profiles were described successfully and all predicted area under the curve (AUC) values were within 2-fold of the observed values. The increase in RUX exposure was predicted with a DDI ratio of 1.21 (C\(_{max}\)) and 1.59 (AUC). Standard dosing in patients with GvHD led to higher RUX exposure than expected, suggesting further dose reduction if combined with POS. The developed model can serve as a starting point for further simulations of the implemented DDI and can be extended to further perpetrators of CYP-mediated PK-DDIs or disease-specific physiological changes.
Chemical warfare or terrorism attacks with organophosphates may place intoxicated subjects under immediate life-threatening and psychologically demanding conditions. Antidotes, such as the oxime HI-6, which must be formulated as a powder for reconstitution reflecting the molecule’s light sensitivity and instability in aqueous solutions, dramatically improve recovery—but only if used soon after exposure. Muscle tremors, anxiety, and loss of consciousness after exposure jeopardize proper administration, translating into demanding specifications for the dissolution of HI-6. Reflecting the patients’ catastrophic situation and anticipated desire to react immediately to chemical weapon exposure, the dissolution should be completed within ten seconds. We are developing multi-dose and single-dose autoinjectors to reliably meet these dissolution requirements. The temporal and spatial course of dissolution within the various autoinjector designs was profiled colorimetrically. Based on these colorimetric insights with model dyes, we developed experimental setups integrating online conductometry to push experiments toward the relevant molecule, HI-6. The resulting blueprints for autoinjector designs integrated small-scale rotor systems, boosting dissolution across a wide range of viscosities, and meeting the required dissolution specifications driven by the use of these drug products in extreme situations.
The 2- and 2,7- substituted para-N-methylpyridinium pyrene cations show high-affinity intercalation into ds-DNAs, whereas their non-methylated analogues interacted with ds-DNA/RNA only in the protonated form (at pH 5), but not at physiological conditions (pH 7). The fluorescence from non-methylated analogues was strongly dependent on the protonation of the pyridines; consequently, they act as fluorescence ratiometric probes for simultaneous detection of both ds-DNA and BSA at pH 5, relying on the ratio between intensities at 420 nm (BSA specific) and 520 nm (DNA specific), whereby exclusively ds-DNA sensing could be switched-off by adjustment to pH 7. Only methylated, permanently charged pyrenes show photoinduced cleavage of circular DNA, attributed to pyrene-mediated irradiation-induced production of singlet oxygen. Consequently, the moderate toxicity of these cations against human cell lines is strongly increased upon irradiation. Detailed studies revealed increased total ROS production in cells treated by the compounds studied, accompanied by cell swelling and augmentation of cellular complexity. The most photo-active 2-para-N-methylpyridinium pyrene showed significant localization at mitochondria, its photo-bioactivity likely due to mitochondrial DNA damage. Other derivatives were mostly non-selectively distributed between various cytoplasmic organelles, thus being less photoactive.
Overexpressed c-Myc sensitizes cells to TH1579, a mitotic arrest and oxidative DNA damage inducer
(2022)
Previously, we reported that MTH1 inhibitors TH588 and TH1579 selectively induce oxidative damage and kill Ras-expressing or -transforming cancer cells, as compared to non-transforming immortalized or primary cells. While this explains the impressive anti-cancer properties of the compounds, the molecular mechanism remains elusive. Several oncogenes induce replication stress, resulting in under replicated DNA and replication continuing into mitosis, where TH588 and TH1579 treatment causes toxicity and incorporation of oxidative damage. Hence, we hypothesized that oncogene-induced replication stress explains the cancer selectivity. To test this, we overexpressed c-Myc in human epithelial kidney cells (HA1EB), resulting in increased proliferation, polyploidy and replication stress. TH588 and TH1579 selectively kill c-Myc overexpressing clones, enforcing the cancer cell selective killing of these compounds. Moreover, the toxicity of TH588 and TH1579 in c-Myc overexpressing cells is rescued by transcription, proteasome or CDK1 inhibitors, but not by nucleoside supplementation. We conclude that the molecular toxicological mechanisms of how TH588 and TH1579 kill c-Myc overexpressing cells have several components and involve MTH1-independent proteasomal degradation of c-Myc itself, c-Myc-driven transcription and CDK activation.
Staphylococcus aureus asymptomatically colonizes the nasal cavity of mammals, but it is also a leading cause of life-threatening infections. Most human nasal isolates carry Sa3 phages, which integrate into the bacterial hlb gene encoding a sphingomyelinase. The virulence factor-encoding genes carried by the Sa3-phages are highly human-specific, and most animal strains are Sa3 negative. Thus, both insertion and excision of the prophage could potentially confer a fitness advantage to S. aureus. Here, we analyzed the phage life cycle of two Sa3 phages, Φ13 and ΦN315, in different phage-cured S. aureus strains. Based on phage transfer experiments, strains could be classified into low (8325-4, SH1000, and USA300c) and high (MW2c and Newman-c) transfer strains. High-transfer strains promoted the replication of phages, whereas phage adsorption, integration, excision, or recA transcription was not significantly different between strains. RNASeq analyses of replication-deficient lysogens revealed no strain-specific differences in the CI/Mor regulatory switch. However, lytic genes were significantly upregulated in the high transfer strain MW2c Φ13 compared to strain 8325-4 Φ13. By transcriptional start site prediction, new promoter regions within the lytic modules were identified, which are likely targeted by specific host factors. Such host-phage interaction probably accounts for the strain-specific differences in phage replication and transfer frequency. Thus, the genetic makeup of the host strains may determine the rate of phage mobilization, a feature that might impact the speed at which certain strains can achieve host adaptation.
Blue nevus is a benign melanocytic lesion, typically asymptomatic and of unknown etiology. Several histologic and clinical variants have been distinguished, the most frequent being common blue nevus, cellular blue nevus, and combined blue nevus. Although melanocytic nevi with a satellite lesion are usually suggestive of locally advanced malignant melanoma, very few cases of blue nevi with satellite lesions have been reported. The diagnosis of common or cellular blue nevi is generally straightforward; however, the presence of structures such as irregular edges or satellitosis are highly suggestive for malignancy, and differential diagnoses such as locally advanced malignant melanoma and malignant blue nevus should be considered. Recurrent blue nevi can display atypical features not seen in the primary lesion, such as pleomorphism and mitotic activity. They usually tend to follow a benign course; however, in some cases, recurrence may indicate malignant transformation. We here report the unique case of a 64-year-old woman with a recurrent cellular blue nevus accompanied by satellite lesions. Such a biological behavior resulting in a clinical presentation as a melanoma-like lesion is a rarity in blue nevus and has not been described before.
Background: This randomized clinical trial was conducted to assess whether sleep bruxism (SB) is associated with an increased rate of technical complications (ceramic defects) in lithium disilicate (LiDi) or zirconia (Z) molar single crowns (SCs). Methods: Adult patients were classified as affected or unaffected by SB based on structured questionnaires, clinical signs, and overnight portable electromyography (BruxOff) and block randomized into four groups according to SB status and crown material (LiDi or Z): LiDi-SB (n = 29), LiDi-no SB (n = 24), Z-SB (n = 23), and Z-no SB (n = 27). Differences in technical complications (main outcome) and survival and success rates (secondary outcomes) one year after crown cementation were assessed using Fisher’s exact test with significance level α = 0.05. Results: No technical complications occurred. Restoration survival rates were 100% in the LiDi-SB and LiDi-no SB groups, 95.7% in the Z-SB group, and 96.3% in the Z-no SB group (p > 0.999). Success rates were 96.6% in the LiDi-SB group, 95.8% in the LiDi-no SB group (p > 0.999), 91.3% in the Z-SB group, and 96.3% in the Z-no SB group (p ≥ 0.588). Conclusions: With a limited observation time and sample size, no effect of SB on technical complication, survival, and success rates of molar LiDi and Z SCs was detected.
Background: Extracorporeal hemadsorption eliminates proinflammatory mediators in critically ill patients with hyperinflammation. The use of a pumpless extracorporeal hemadsorption technique allows its early usage prior to organ failure and the need for an additional medical device. In our animal model, we investigated the feasibility of pumpless extracorporeal hemadsorption over a wide range of mean arterial pressures (MAP). Methods: An arteriovenous shunt between the femoral artery and femoral vein was established in eight pigs. The hemadsorption devices were inserted into the shunt circulation; four pigs received CytoSorb\(^®\) and four Oxiris\(^®\) hemadsorbers. Extracorporeal blood flow was measured in a range between mean arterial pressures of 45–85 mmHg. Mean arterial pressures were preset using intravenous infusions of noradrenaline, urapidil, or increased sedatives. Results: Extracorporeal blood flows remained well above the minimum flows recommended by the manufacturers throughout all MAP steps for both devices. Linear regression resulted in CytoSorb\(^®\) blood flow [mL/min] = 4.226 × MAP [mmHg] − 3.496 (R-square 0.8133) and Oxiris\(^®\) blood flow [mL/min] = 3.267 × MAP [mmHg] + 57.63 (R-square 0.8708), respectively. Conclusion: Arteriovenous pumpless extracorporeal hemadsorption resulted in sufficient blood flows through both the CytoSorb\(^®\) and Oxiris\(^®\) devices over a wide range of mean arterial blood pressures and is likely an intriguing therapeutic option in the early phase of septic shock or hyperinflammatory syndromes.
Active vitamin D (1,25(OH)2D3) is known to exert direct anti-cancer actions on various malignant tissues through binding to the vitamin D receptor (VDR). These effects have been demonstrated in breast, prostate, renal and thyroid cancers, which all have a high propensity to metastasise to bone. In addition, there is evidence that vitamin D catabolism via 24-hydroxylase (CYP24A1) is altered in tumour cells, thus, reducing local active vitamin D levels in cancer cells. The aim of this study was to assess VDR and CYP24A1 expression in various types of bone metastases by using immunohistochemistry. Overall, a high total VDR protein expression was detected in 59% of cases (39/66). There was a non-significant trend of high-grade tumours towards the low nuclear VDR expression (p = 0.07). Notably, patients with further distant metastases had a reduced nuclear VDR expression (p = 0.03). Furthermore, a high CYP24A1 expression was detected in 59% (39/66) of bone metastases. There was a significant positive correlation between nuclear VDR and CYP24A1 expression (p = 0.001). Collectively, the VDR and CYP24A1 were widely expressed in a multitude of bone metastases, pointing to a potential role of vitamin D signalling in cancer progression. This is of high clinical relevance, as vitamin D deficiency is frequent in patients with bone metastases.
The variable regions (V1–V9) of the 18S rDNA are routinely used in barcoding and phylogenetics. In handling these data for trypanosomes, we have noticed a misunderstanding that has apparently taken a life of its own in the literature over the years. In particular, in recent years, when studying the phylogenetic relationship of trypanosomes, the use of V7/V8 was systematically established. However, considering the current numbering system for all other organisms (including other Euglenozoa), V7/V8 was never used. In Maia da Silva et al. [Parasitology 2004, 129, 549–561], V7/V8 was promoted for the first time for trypanosome phylogenetics, and since then, more than 70 publications have replicated this nomenclature and even discussed the benefits of the use of this region in comparison to V4. However, the primers used to amplify the variable region of trypanosomes have actually amplified V4 (concerning the current 18S rDNA numbering system).
Complementary currencies have spread to many places around the world at the beginning of the 21st century. Creating sustainable economic cycles and short transport routes are often the goals of introducing them. Due to their manageability, regional currencies can be embedded in debates of regional economics and sustainability. Above all, they are suitable for democratic experiments that can show in real environments whether currency designs work as examples of collaborative communities and research. One of these monetary experiments is the climate bonus, which is linked to the local currency Chiemgauer. The research path goes into the daily routine of a real laboratory to find out which methods would be effective enough to deliver carbon savings. The climate bonus creates a monetary network where people can try out new behaviors in a protected space. As a result, three years after the initiation of the project, carbon reductions are above expectations.
The Niger Delta belongs to the largest swamp and mangrove forests in the world hosting many endemic and endangered species. Therefore, its conservation should be of highest priority. However, the Niger Delta is confronted with overexploitation, deforestation and pollution to a large extent. In particular, oil spills threaten the biodiversity, ecosystem services, and local people. Remote sensing can support the detection of spills and their potential impact when accessibility on site is difficult. We tested different vegetation indices to assess the impact of oil spills on the land cover as well as to detect accumulations (hotspots) of oil spills. We further identified which species, land cover types, and protected areas could be threatened in the Niger Delta due to oil spills. The results showed that the Enhanced Vegetation Index, the Normalized Difference Vegetation Index, and the Soil Adjusted Vegetation Index were more sensitive to the effects of oil spills on different vegetation cover than other tested vegetation indices. Forest cover was the most affected land-cover type and oil spills also occurred in protected areas. Threatened species are inhabiting the Niger Delta Swamp Forest and the Central African Mangroves that were mainly affected by oil spills and, therefore, strong conservation measures are needed even though security issues hamper the monitoring and control.
Family relationships in selective mutism — a comparison group study of children and adolescents
(2022)
Selective mutism (SM) mostly develops early in childhood and this has led to interest into whether there could be differences in relationships in families with SM compared to a control group without SM. Currently, there are merely few empirical studies examining family relationships in SM. A sample of 28 children and adolescents with SM was compared to 33 controls without SM. The groups were investigated using self-report questionnaires (Selective Mutism Questionnaire, Child-Parent Relationship Test—Child Version) for the assessment of SM and family relationships. Children with SM did not report a significantly different relationship to their mothers compared with the control group without SM. However, the scores in respect to the relationship to their fathers were significantly lower in cohesion, identification and autonomy compared with children without SM. Relationships in families with SM should be considered more in therapy.
Serotonin (5-hydroxytryptamine, 5-HT) as well as noradrenaline (NA) are key modulators of various fundamental brain functions including the control of appetite. While manipulations that alter brain serotoninergic signaling clearly affect body weight, studies implicating 5-HT transporters and NA transporters (5-HTT and NAT, respectively) as a main drug treatment target for human obesity have not been conclusive. The aim of this positron emission tomography (PET) study was to investigate how these central transporters are associated with changes of body weight after 6 months of dietary intervention or Roux-en-Y gastric bypass (RYGB) surgery in order to assess whether 5-HTT as well as NAT availability can predict weight loss and consequently treatment success. The study population consisted of two study cohorts using either the 5-HTT-selective radiotracer [\(^{11}\)C]DASB to measure 5-HTT availability or the NAT-selective radiotracer [\(^{11}\)C]MRB to assess NAT availability. Each group included non-obesity healthy participants, patients with severe obesity (body mass index, BMI, >35 kg/m\(^2\)) following a conservative dietary program (diet) and patients undergoing RYGB surgery within a 6-month follow-up. Overall, changes in BMI were not associated with changes of both 5-HTT and NAT availability, while 5-HTT availability in the dorsal raphe nucleus (DRN) prior to intervention was associated with substantial BMI reduction after RYGB surgery and inversely related with modest BMI reduction after diet. Taken together, the data of our study indicate that 5-HTT and NAT are involved in the pathomechanism of obesity and have the potential to serve as predictors of treatment outcomes.
Towards a consensus on an ICF-based classification system for horizontal sound-source localization
(2022)
The study aimed to develop a consensus classification system for the reporting of sound localization testing results, especially in the field of cochlear implantation. Against the background of an overview of the wide variations present in localization testing procedures and reporting metrics, a novel classification system was proposed to report localization errors according to the widely accepted International Classification of Functioning, Disability and Health (ICF) framework. The obtained HEARRING_LOC_ICF scale includes the ICF graded scale: 0 (no impairment), 1 (mild impairment), 2 (moderate impairment), 3 (severe impairment), and 4 (complete impairment). Improvement of comparability of localization results across institutes, localization testing setups, and listeners was demonstrated by applying the classification system retrospectively to data obtained from cohorts of normal-hearing and cochlear implant listeners at our institutes. The application of our classification system will help to facilitate multi-center studies, as well as allowing better meta-analyses of data, resulting in improved evidence-based practice in the field.
Inpatient rehabilitation (IR) is a common postoperative protocol after total knee replacement (TKA). Because IR is expensive and should therefore be justified, this study determined the difference in knee function one year after TKA in patients treated with IR or outpatient rehabilitation, fast-track rehabilitation (FTR) in particular, which also entails a reduced hospital length of stay. A total of 205 patients were included in this multi-center prospective cohort study. Of the patients, 104 had primary TKA at a German university hospital and received IR, while 101 had primary TKA at a Canadian university hospital and received FTR. Patients receiving IR or FTR were matched by pre-operative demographics and knee function. Oxford Knee Score (OKS), Western Ontario and McMaster Universities Arthritis Index (WOMAC), and EuroQol visual analogue scale (EQ-VAS) determined knee function one year after surgery. Patients receiving IR had a 2.8-point lower improvement in OKS (p = 0.001), a 6.7-point lower improvement in WOMAC (p = 0.063), and a 12.3-point higher improvement in EQ-VAS (p = 0.281) than patients receiving FTR. IR does not provide long-term benefits to patient recovery after primary uncomplicated TKA under the current rehabilitation regime.
Background: A concern about kinematically aligned (KA) total knee arthroplasty (TKA) is that it relies on femoral components designed for mechanical alignment (MAd-FC) that could affect patellar tracking, in part, because of a trochlear groove orientation that is typically 6° from vertical. KA sets the femoral component coincident to the patient’s pre-arthritic distal and posterior femoral joint lines and restores the Q-angle, which varies widely. Relative to KA and the native knee, aligning the femoral component with MA changes most distal joint lines and Q-angles, and rotates the posterior joint line externally laterally covering the anterior femoral resection. Whether switching from a MAd- to a KAd-FC with a wider trochlear groove orientation of 20.5° from vertical results in radiographic measures known to promote patellar tracking is unknown. The primary aim was to determine whether a KAd-FC sets the trochlear groove lateral to the quadriceps line of force (QLF), better laterally covers the anterior femoral resection, and reduces lateral patella tilt relative to a MAd-FC. The secondary objective was to determine at six weeks whether the KAd-FC resulted in a higher complication rate, less knee extension and flexion, and lower clinical outcomes. Methods: Between April 2019 and July 2022, two surgeons performed sequential bilateral unrestricted caliper-verified KA TKA with manual instruments on thirty-six patients with a KAd- and MAd-FC in opposite knees. An observer measured the angle between a line best-fit to the deepest valley of the trochlea and a line representing the QLF that indicated the patient’s Q-angle. When the trochlear groove was lateral or medial relative to the QLF, the angle is denoted + or −, and the femoral component included or excluded the patient’s Q-angle, respectively. Software measured the lateral undercoverage of the anterior femoral resection on a Computed Tomography (CT) scan, and the patella tilt angle (PTA) on a skyline radiograph. Complications, knee extension and flexion measurements, Oxford Knee Score, KOOS Jr, and Forgotten Joint Score were recorded pre- and post-operatively (at 6 weeks). A paired Student’s T-test determined the difference between the KA TKAs with a KAd-FC and MAd-FC with a significance set at p < 0.05. Results: The final analysis included thirty-five patients. The 20.5° trochlear groove of the KAd-FC was lateral to the QLF in 100% (15 ± 3°) of TKAs, which was greater than the 69% (1 ± 3°) lateral to the QLF with the 6° trochlear groove of the MAd-FC (p < 0.001). The KAd-FC’s 2 ± 1.9 mm lateral undercoverage of the anterior femoral resection was less than the 4.4 ± 1.5 mm for the MAd-FC (p < 0.001). The PTA, complication rate, knee extension and flexion, and clinical outcome measures did not differ between component designs. Conclusions: The KA TKA with a KAd-FC resulted in a trochlear groove lateral to the QLF that included the Q-angle in all patients, and negligible lateral undercoverage of the anterior femoral resection. These newly described radiographic parameters could be helpful when investigating femoral components designed for KA with the intent of promoting patellofemoral kinematics.
Ionic liquids-assisted ring opening of three-membered heterocycles with thio- and seleno-silanes
(2022)
Ring opening reactions of strained heterocycles (epoxides, aziridines, thiiranes) by silyl chalcogenides, such as thiosilanes and selenosilanes, can be efficiently performed in a variety of ionic liquids, which can behave as reaction media and in some cases also as catalysts. This protocol enables an alternative access to β-functionalized sulfides and selenides under mild conditions.
Introduction: 2–8% of all gastric cancer occurs at a younger age, also known as early-onset gastric cancer (EOGC). The aim of the present work was to use clinical registry data to classify and characterize the young cohort of patients with gastric cancer more precisely. Methods: German Cancer Registry Group of the Society of German Tumor Centers—Network for Care, Quality and Research in Oncology (ADT)was queried for patients with gastric cancer from 2000–2016. An approach that stratified relative distributions of histological subtypes of gastric adenocarcinoma according to age percentiles was used to define and characterize EOGC. Demographics, tumor characteristics, treatment and survival were analyzed. Results: A total of 46,110 patients were included. Comparison of different groups of age with incidences of histological subtypes showed that incidence of signet ring cell carcinoma (SRCC) increased with decreasing age and exceeded pooled incidences of diffuse and intestinal type tumors in the youngest 20% of patients. We selected this group with median age of 53 as EOGC. The proportion of female patients was lower in EOGC than that of elderly patients (43% versus 45%; p < 0.001). EOGC presented more advanced and undifferentiated tumors with G3/4 stages in 77% versus 62%, T3/4 stages in 51% versus 48%, nodal positive tumors in 57% versus 53% and metastasis in 35% versus 30% (p < 0.001) and received less curative treatment (42% versus 52%; p < 0.001). Survival of EOGC was significantly better (five-years survival: 44% versus 31% (p < 0.0001), with age as independent predictor of better survival (HR 0.61; p < 0.0001). Conclusion: With this population-based registry study we were able to objectively define a cohort of patients referred to as EOGC. Despite more aggressive/advanced tumors and less curative treatment, survival was significantly better compared to elderly patients, and age was identified as an independent predictor for better survival.
As radiotherapy is an important part of the treatment in a variety of pediatric tumors of the central nervous system (CNS), proton beam therapy (PBT) plays an evolving role due to its potential benefits attributable to the unique dose distribution, with the possibility to deliver high doses to the target volume while sparing surrounding tissue. Children receiving PBT for an intracranial tumor between August 2013 and October 2017 were enrolled in the prospective registry study KiProReg. Patient’s clinical data including treatment, outcome, and follow-up were analyzed using descriptive statistics, Kaplan–Meier, and Cox regression analysis. Adverse events were scored according to the Common Terminology Criteria for Adverse Events (CTCAE) 4.0 before, during, and after PBT. Written reports of follow-up imaging were screened for newly emerged evidence of imaging changes, according to a list of predefined keywords for the first 14 months after PBT. Two hundred and ninety-four patients were enrolled in this study. The 3-year overall survival of the whole cohort was 82.7%, 3-year progression-free survival was 67.3%, and 3-year local control was 79.5%. Seventeen patients developed grade 3 adverse events of the CNS during long-term follow-up (new adverse event n = 7; deterioration n = 10). Two patients developed vision loss (CTCAE 4°). This analysis demonstrates good general outcomes after PBT.
(1) Background: The recurrence of glioblastoma multiforme (GBM) is mainly due to invasion of the surrounding brain tissue, where organic solutes, including glucose and inositol, are abundant. Invasive cell migration has been linked to the aberrant expression of transmembrane solute-linked carriers (SLC). Here, we explore the role of glucose (SLC5A1) and inositol transporters (SLC5A3) in GBM cell migration. (2) Methods: Using immunofluorescence microscopy, we visualized the subcellular localization of SLC5A1 and SLC5A3 in two highly motile human GBM cell lines. We also employed wound-healing assays to examine the effect of SLC inhibition on GBM cell migration and examined the chemotactic potential of inositol. (3) Results: While GBM cell migration was significantly increased by extracellular inositol and glucose, it was strongly impaired by SLC transporter inhibition. In the GBM cell monolayers, both SLCs were exclusively detected in the migrating cells at the monolayer edge. In single GBM cells, both transporters were primarily localized at the leading edge of the lamellipodium. Interestingly, in GBM cells migrating via blebbing, SLC5A1 and SLC5A3 were predominantly detected in nascent and mature blebs, respectively. (4) Conclusion: We provide several lines of evidence for the involvement of SLC5A1 and SLC5A3 in GBM cell migration, thereby complementing the migration-associated transportome. Our findings suggest that SLC inhibition is a promising approach to GBM treatment.
Cutaneous squamous cell carcinoma (cSCC) is a common malignancy of the skin and has an overall favorable outcome, except for patients with an advanced stage of the disease. The efficacy of checkpoint inhibitors (CPI) for advanced cSCC has been demonstrated in recent clinical studies, but data from real-world cohorts and trial-ineligible cSCC patients are limited. We retrospectively investigated patients with advanced cSCC who have been treated with CPI in a first-line setting at eight German skin cancer centers registered within the multicenter registry ADOReg. Clinical outcome parameters including response, progression-free (PFS) and overall survival (OS), time-to-next-treatment (TTNT), and toxicity were analyzed and have been stratified by the individual immune status. Among 39 evaluable patients, the tumor response rate (rwTRR) was 48.6%, the median PFS was 29.0 months, and the median OS was not reached. In addition, 9 patients showed an impaired immune status due to immunosuppressive medication or hematological diseases. Our data demonstrated that CPI also evoked tumor responses among immunocompromised patients (rwTRR: 48.1 vs. 50.0%), although these responses less often resulted in durable remissions. In line with this, the median PFS (11 vs. 40 months, p = 0.059), TTNT (12 months vs. NR, p = 0.016), and OS (29 months vs. NR, p < 0.001) were significantly shorter for this patient cohort. CPI therapy was well tolerated in both subcohorts with 15% discontinuing therapy due to toxicity. Our real-world data show that first-line CPI therapy produced strong and durable responses among patients with advanced cSCC. Immunocompromised patients were less likely to achieve long-term benefit from anti-PD1 treatment, despite similar tumor response rates.
Current data show that resilience is an important factor in cancer patients’ well-being. We aim to explore the resilience of patients with lower grade glioma (LGG) and the potentially influencing factors. We performed a cross-sectional assessment of adult patients with LGG who were enrolled in the LoG-Glio registry. By phone interview, we administered the following measures: Resilience Scale (RS-13), distress thermometer, Montreal Cognitive Assessment Test for visually impaired patients (MoCA-Blind), internalized stigmatization by brain tumor (ISBI), Eastern Cooperative Oncological Group performance status (ECOG), patients’ perspective questionnaire (PPQ) and typical clinical parameters. We calculated correlations and multivariate regression models. Of 74 patients who were assessed, 38% of those showed a low level of resilience. Our results revealed significant correlations of resilience with distress (p < 0.001, −0.49), MOCA (p = 0.003, 0.342), ECOG (p < 0.001, −0.602), stigmatization (p < 0.001, −0.558), pain (p < 0.001, −0.524), and occupation (p = 0.007, 0.329). In multivariate analyses, resilience was negatively associated with elevated ECOG (p = 0.020, β = −0.383) and stigmatization levels (p = 0.008, β = −0.350). Occupation showed a tendency towards a significant association with resilience (p = 0.088, β = −0.254). Overall, low resilience affected more than one third of our cohort. Low functional status is a specific risk factor for low resilience. The relevant influence of stigmatization on resilience is a novel finding for patients suffering from a glioma and should be routinely identified and targeted in clinical routine.
Despite some critical voices, in German linguistics the concept of confix can meanwhile be considered as an established morpheme category. Schmidt (1987) introduced the term into German to describe bound morphemes that are lexical, but not inflectable. Since the 2000s, an increasing number of publications deal with the phenomenon and the term has begun to enter linguistic reference works as well. In French, the situation is completely different due to the structure of the language (poor in compounds and mostly post-determinative). Although the term and the concept have originall y been coined by the French structuralist André Martinet ([1961] \(^3\)1980 ), the denomination itself is barely present in Romance linguistics. French researchers usually take different approaches to discuss the phenomenon (e.g., neoclassical compounds, constructed lexemes). In Italian, the denominations confisso/ confissazione are first used by De Mauro (1999), who adopts both the term and concept directly from Martinet; moreover, they can be found in some contributions on word formation and lexicology (e.g., Adamo/Della Valle 2008). Nevertheless, the Italian termino-logy remains heterogeneous, with some researchers still using the terms prefissoide/suffissoide coined by Migliorini (1963). As I will show by comparing the languages in question, the terminology and the concept of confixes vary greatly between Romance and Germanic languages.
Background: Primary cutaneous follicular B-cell lymphoma (PCFBCL) represents an indolent subtype of Non-Hodgkin’s lymphomas, being clinically characterized by slowly growing tumors of the skin and common cutaneous relapses, while only exhibiting a low propensity for systemic dissemination or fatal outcome. Up to now, only few studies have investigated underlying molecular alterations of PCFBCL with respect to somatic mutations. Objectives: Our aim was to gain deeper insight into the pathogenesis of PCFBCL and to delineate discriminatory molecular features of this lymphoma subtype. Methods: We performed hybridization-based panel sequencing of 40 lymphoma-associated genes of 10 cases of well-characterized PCFBCL. In addition, we included two further ambiguous cases of atypical B-cell-rich lymphoid infiltrate/B-cell lymphoma of the skin for which definite subtype attribution had not been possible by routine investigations. Results: In 10 out of 12 analyzed cases, we identified genetic alterations within 15 of the selected 40 target genes. The most frequently detected alterations in PCFBCL affected the TNFRSF14, CREBBP, STAT6 and TP53 genes. Our analysis unrevealed novel mutations of the BCL2 gene in PCFBCL. All patients exhibited an indolent clinical course. Both the included arbitrary cases of atypical B-cell-rich cutaneous infiltrates showed somatic mutations within the FAS gene. As these mutations have previously been designated as subtype-specific recurrent alterations in primary cutaneous marginal zone lymphoma (PCMZL), we finally favored the diagnosis of PCMZL in these two cases based on these molecular findings. Conclusions: To conclude, our molecular data support that PCFBCL shows distinct somatic mutations which may aid to differentiate PCFBCL from pseudo-lymphoma as well as from other indolent and aggressive cutaneous B-cell lymphomas. While the detected genetic alterations of PCFBCL did not turn out to harbor any prognostic value in our cohort, our molecular data may add adjunctive discriminatory features for diagnostic purposes on a molecular level.
(1) Background: molecular tumor boards (MTBs) are crucial instruments for discussing and allocating targeted therapies to suitable cancer patients based on genetic findings. Currently, limited evidence is available regarding the regional impact and the outreach component of MTBs; (2) Methods: we analyzed MTB patient data from four neighboring Bavarian tertiary care oncology centers in Würzburg, Erlangen, Regensburg, and Augsburg, together constituting the WERA Alliance. Absolute patient numbers and regional distribution across the WERA-wide catchment area were weighted with local population densities; (3) Results: the highest MTB patient numbers were found close to the four cancer centers. However, peaks in absolute patient numbers were also detected in more distant and rural areas. Moreover, weighting absolute numbers with local population density allowed for identifying so-called white spots—regions within our catchment that were relatively underrepresented in WERA MTBs; (4) Conclusions: investigating patient data from four neighboring cancer centers, we comprehensively assessed the regional impact of our MTBs. The results confirmed the success of existing collaborative structures with our regional partners. Additionally, our results help identifying potential white spots in providing precision oncology and help establishing a joint WERA-wide outreach strategy.
Li-Fraumeni-syndrome (LFS) is a rare, highly penetrant cancer predisposition syndrome (CPS) caused by pathogenic variants (PVs) in TP53. Physical activity (PA) and a Mediterranean diet lead to cancer reduction or survival benefits and increased quality of life (QoL), but this is yet unstudied among LFS. TP53 PV carriers (PVC) and their relatives were questioned on dietary patterns (Mediterranean Diet Adherence Screener), PA (Freiburg Questionnaire), QoL (Short-form-Health-Survey-12), smoking, alcohol consumption and perception of cancer risk in a German bi-centric study from March 2020–June 2021. The study enrolled 70 PVC and 43 relatives. Women compared to men (6.49 vs. 5.38, p = 0.005) and PVC to relatives (6.59 vs. 5.51; p = 0.006) showed a healthier diet, associated with participation in surveillance (p = 0.04) and education (diet p = 0.02 smoking p = 0.0003). Women smoked less (2.91 vs. 5.91 packyears; p = 0.03), psychological well-being was higher among men (SF-12: males 48.06 vs. females 41.94; p = 0.004). PVC rated their own cancer risk statistically higher than relatives (72% vs. 38%, p < 0.001) however, cancer risk of the general population was rated lower (38% vs. 70%, p < 0.001). A relative’s cancer-related death increased the estimated personal cancer risk (p = 0.01). The possibilities of reducing cancer through self-determined health behavior among PVC and relatives has not yet been exhausted. Educating families with a CPS on cancer-preventive behavior requires further investigation with regard to acceptance and real-life implementation.
Alzheimer’s disease (AD), the most common cause of dementia in the elderly, is a neurodegenerative disorder associated with neurovascular dysfunction, cognitive decline, and the accumulation of amyloid β peptide (Aβ) in the brain and tau-related lesions in neurons termed neurofibrillary tangles (NFTs). Aβ deposits and NFT formation are the central pathological hallmarks in AD brains, and the majority of AD cases have been shown to exhibit a complex combination of systemic comorbidities. While AD is the foremost common cause of dementia in the elderly, age-related hearing loss (ARHL) is the most predominant sensory deficit in the elderly. During aging, chronic inflammation and resulting endothelial dysfunction have been described and might be key contributors to AD; we discuss an intriguing possible link between inner ear strial microvascular pathology and blood–brain barrier pathology and present ARHL as a potentially modifiable and treatable risk factor for AD development. We present compelling evidence that ARHL might well be seen as an important risk factor in AD development: progressive hearing impairment, leading to social isolation, and its comorbidities, such as frailty, falls, and late-onset depression, link ARHL with cognitive decline and increased risk of dementia, rendering it tempting to speculate that ARHL might be a potential common molecular and pathological trigger for AD. Additionally, one could speculate that amyloid-beta might damage the blood–labyrinth barrier as it does to the blood–brain barrier, leading to ARHL pathology. Finally, there are options for the treatment of ARHL by targeted neurotrophic factor supplementation to the cochlea to improve cognitive outcomes; they can also prevent AD development and AD-related comorbidity in the future.
Survival motor neuron (SMN) is an essential and ubiquitously expressed protein that participates in several aspects of RNA metabolism. SMN deficiency causes a devastating motor neuron disease called spinal muscular atrophy (SMA). SMN forms the core of a protein complex localized at the cytoplasm and nuclear gems and that catalyzes spliceosomal snRNP particle synthesis. In cultured motor neurons, SMN is also present in dendrites and axons, and forms part of the ribonucleoprotein transport granules implicated in mRNA trafficking and local translation. Nevertheless, the distribution, regulation, and role of SMN at the axons and presynaptic motor terminals in vivo are still unclear. By using conventional confocal microscopy and STED super-resolution nanoscopy, we found that SMN appears in the form of granules distributed along motor axons at nerve terminals. Our fluorescence in situ hybridization and electron microscopy studies also confirmed the presence of β-actin mRNA, ribosomes, and polysomes in the presynaptic motor terminal, key elements of the protein synthesis machinery involved in local translation in this compartment. SMN granules co-localize with the microtubule-associated protein 1B (MAP1B) and neurofilaments, suggesting that the cytoskeleton participates in transporting and positioning the granules. We also found that, while SMN granules are physiologically downregulated at the presynaptic element during the period of postnatal maturation in wild-type (non-transgenic) mice, they accumulate in areas of neurofilament aggregation in SMA mice, suggesting that the high expression of SMN at the NMJ, together with the cytoskeletal defects, contribute to impairing the bi-directional traffic of proteins and organelles between the axon and the presynaptic terminal.
Alzheimer’s disease (AD) is considered a chronic and debilitating neurological illness that is increasingly impacting older-age populations. Some proteins, including clusterin (CLU or apolipoprotein J) transporter, can be linked to AD, causing oxidative stress. Therefore, its activity can affect various functions involving complement system inactivation, lipid transport, chaperone activity, neuronal transmission, and cellular survival pathways. This transporter is known to bind to the amyloid beta (Aβ) peptide, which is the major pathogenic factor of AD. On the other hand, this transporter is also active at the blood–brain barrier (BBB), a barrier that prevents harmful substances from entering and exiting the brain. Therefore, in this review, we discuss and emphasize the role of the CLU transporter and CLU-linked molecular mechanisms at the BBB interface in the pathogenesis of AD.
Distinguishing composite remnants from tooth structure after trauma splint removal can be challenging. This study aimed to compare the Fluorescence-aided Identification Technique (FIT) with conventional light illumination (CONV) in terms of accuracy and time required for the detection of composite remnants after trauma splint removal. Ten bovine tooth models containing anterior teeth from 12 to 22 with composite remnants after trauma splint removal were used. These models were examined by 10 students and 10 general dentists. Each examiner assessed the 10 models using CONV or FIT three times with an interval of 2 weeks each using a prototype fluorescence-inducing headlamp with a spectral bandwidth of (405 ± 7) nm for FIT and a dental unit lamp for CONV. The examiners charted the location of identified composite remnants, and the procedure time needed for each method was recorded. Statistical analysis was performed with R 3.2.2 software with a significance level of α = 5%. FIT was more accurate and less time-consuming than CONV (p < 0.001). There were no significant differences between dentists and students concerning accuracy (CONV: p = 0.26; FIT: p = 0.73). Students performed FIT significantly faster than the dentists (p < 0.001). FIT is a quick and reliable method of identifying composite remnants after trauma splint removal.
The surface urban heat island (SUHI) affects the quality of urban life. Because varying urban structures have varying impacts on SUHI, it is crucial to understand the impact of land use/land cover characteristics for improving the quality of life in cities and urban health. Satellite-based data on land surface temperatures (LST) and derived land use/cover pattern (LUCP) indicators provide an efficient opportunity to derive the required data at a large scale. This study explores the seasonal and diurnal variation of spatial associations from LUCP and LST employing Pearson correlation and ordinary least squares regression analysis. Specifically, Landsat-8 images were utilized to derive LSTs in four seasons, taking Berlin as a case study. The results indicate that: (1) in terms of land cover, hot spots are mainly distributed over transportation, commercial and industrial land in the daytime, while wetlands were identified as hot spots during nighttime; (2) from the land composition indicators, the normalized difference built-up index (NDBI) showed the strongest influence in summer, while the normalized difference vegetation index (NDVI) exhibited the biggest impact in winter; (3) from urban morphological parameters, the building density showed an especially significant positive association with LST and the strongest effect during daytime.
Mitochondria are central organelles in the homeostasis of the cardiovascular system via the integration of several physiological processes, such as ATP generation via oxidative phosphorylation, synthesis/exchange of metabolites, calcium sequestration, reactive oxygen species (ROS) production/buffering and control of cellular survival/death. Mitochondrial impairment has been widely recognized as a central pathomechanism of almost all cardiovascular diseases, rendering these organelles important therapeutic targets. Mitochondrial dysfunction has been reported to occur in the setting of drug-induced toxicity in several tissues and organs, including the heart. Members of the drug classes currently used in the therapeutics of cardiovascular pathologies have been reported to both support and undermine mitochondrial function. For the latter case, mitochondrial toxicity is the consequence of drug interference (direct or off-target effects) with mitochondrial respiration/energy conversion, DNA replication, ROS production and detoxification, cell death signaling and mitochondrial dynamics. The present narrative review aims to summarize the beneficial and deleterious mitochondrial effects of common cardiovascular medications as described in various experimental models and identify those for which evidence for both types of effects is available in the literature.
Cyclodextrins (CDs) are cyclic oligosaccharide structures that could be used for theranostic applications in personalized medicine. These compounds have been widely utilized not only for enhancing drug solubility, stability, and bioavailability but also for controlled and targeted delivery of small molecules. These compounds can be complexed with various biomolecules, such as peptides or proteins, via host-guest interactions. CDs are amphiphilic compounds with water-hating holes and water-absorbing surfaces. Architectures of CDs allow the drawing and preparation of CD-based polymers (CDbPs) with optimal pharmacokinetic and pharmacodynamic properties. These polymers can be cloaked with protein corona consisting of adsorbed plasma or extracellular proteins to improve nanoparticle biodistribution and half-life. Besides, CDs have become famous in applications ranging from biomedicine to environmental sciences. In this review, we emphasize ongoing research in biomedical fields using CD-based centered, pendant, and terminated polymers and their interactions with protein corona for theranostic applications. Overall, a perusal of information concerning this novel approach in biomedicine will help to implement this methodology based on host-guest interaction to improve therapeutic and diagnostic strategies.