Refine
Year of publication
Document Type
- Preprint (689)
- Article (460)
- Conference Proceeding (4)
- Report (3)
- Review (1)
- Working Paper (1)
Has Fulltext
- yes (1158)
Is part of the Bibliography
- no (1158)
Keywords
- Heavy Ion Experiments (21)
- Hadron-Hadron Scattering (11)
- Hadron-Hadron scattering (experiments) (11)
- LHC (9)
- Heavy-ion collision (6)
- ALICE experiment (4)
- Collective Flow (4)
- Jets (4)
- Quark-Gluon Plasma (4)
- ALICE (3)
- Epilepsy (3)
- Frieden (3)
- Friedenskonferenz (3)
- Heavy Ions (3)
- Heavy Quark Production (3)
- Jets and Jet Substructure (3)
- MSC (3)
- MSC2013 (3)
- Prostate cancer (3)
- Sicherheitskonferenz (3)
- TAVI (3)
- pp collisions (3)
- radical prostatectomy (3)
- security conference (3)
- Beauty production (2)
- Bipolar disorder (2)
- Charm physics (2)
- Diagnostic markers (2)
- Elliptic flow (2)
- Experimental nuclear physics (2)
- Experimental particle physics (2)
- Heavy-ion collisions (2)
- Lepton-Nucleon Scattering (experiments) (2)
- Machine learning (2)
- München (2)
- Oncology (2)
- Particle Correlations and Fluctuations (2)
- Particle and resonance production (2)
- Particle correlations and fluctuations (2)
- Pb–Pb collisions (2)
- QCD (2)
- Seizure (2)
- Single electrons (2)
- aortic stenosis (2)
- biomarker (2)
- functional outcome (2)
- pelvic packing (2)
- penile cancer (2)
- prostate cancer (2)
- targeted therapy (2)
- 900 GeV (1)
- ACE inhibitor (1)
- AIS (1)
- AKT (1)
- ALICE detector (1)
- AT1 receptor antagonist (1)
- ATM (1)
- Accelerators & Beams (1)
- Accelerators & storage rings (1)
- Alcohol consumption (1)
- Angiomyolipoma (1)
- Anti-nuclei (1)
- Anti-seizure medication (1)
- Anticonvulsant (1)
- Aortic stenosis (1)
- Artesunate (1)
- Artificial Intelligence (1)
- Artificial intelligence (1)
- Atomic & molecular beams (1)
- Atomic and Molecular Physics (1)
- Atomic, Molecular & Optical (1)
- Awareness campaign (1)
- B-slope (1)
- BESIII (1)
- BPDCN (1)
- BPH (1)
- Beam loss (1)
- Benutzeroberfläche (1)
- Biodiversity Data (1)
- Biomarker (1)
- Biomarkers (1)
- Biomedical engineering (1)
- Biomonitoring (1)
- Blood pressure (1)
- Bone cement implantation syndrome (1)
- Boosted Jets (1)
- Botanical Collections (1)
- Breast cancer (1)
- C-clamp (1)
- CDKN2A (1)
- CRPC (1)
- CT (1)
- CVID (1)
- Cancer (1)
- Cancer check up (1)
- Cancer detection and diagnosis (1)
- Cell-to-Cell Spread (1)
- Centrality Class (1)
- Centrality Selection (1)
- Cerebral oxygen saturation (1)
- Cerebrovascular disorders (1)
- Charge-transfer collisions (1)
- Charm quark spatial diffusion coefficient (1)
- Children (1)
- Circadian (1)
- Circular accelerators (1)
- Clinical study (1)
- Coalescence (1)
- Collective Flow, (1)
- Collectivity (1)
- Comparison with QCD (1)
- Computerlinguistik (1)
- Conservation (1)
- Conservation biogeography (1)
- Correlation (1)
- Costs (1)
- Critical point (1)
- Deuteron production (1)
- Diagnostic differentiation (1)
- Diffraction (1)
- Digitization (1)
- Elastic scattering (1)
- Electromagnetic form factors (1)
- Electron-pion identification (1)
- Electronic transitions (1)
- Electroweak interaction (1)
- Esophageal adenocarcinoma (1)
- Europe (1)
- European Society for Immunodeficiencies (ESID) (1)
- Everolimus (1)
- Eyes (1)
- FFLU (1)
- Falciparum (1)
- Femtoscopy (1)
- Fibre/foam sandwich radiator (1)
- Functional outcomes (1)
- FungiScope® registry (1)
- GFAP (1)
- Gadobutrol (1)
- Gadopentate dimeglumine (1)
- Genetic causes of cancer (1)
- Genetic testing (1)
- Genetic wildlife monitoring (1)
- Genetics (1)
- Genetics research (1)
- German PID-NET registry (1)
- Glaucoma (1)
- Gleason Grade Group (1)
- HBT (1)
- HCC (1)
- HNSCC (1)
- Hadron production (1)
- Hadron-Hadron Scattering Heavy (1)
- Hadron-hadron interactions (1)
- Hair sampling (1)
- Hard Scattering (1)
- Heavy Ion Experiment (1)
- Heavy flavor production (1)
- Heavy flavour production (1)
- Heavy ions (1)
- Heavy-Ion Collision (1)
- Heavy-flavor decay electron (1)
- Heavy-flavour decay muons (1)
- Heavy-flavour production (1)
- Herbaria (1)
- Higher moments (1)
- Hip hemiarthroplasty (1)
- Histology (1)
- HoLEP (1)
- Human genetics (1)
- ICU (1)
- IL-10 (1)
- IL-6 (1)
- ISS (1)
- IgG substitution therapy (1)
- Inclusive spectra (1)
- Initial state radiation (1)
- Injury Severity Score (ISS) (1)
- Intensity interferometry (1)
- Invariant Mass Distribution (1)
- Invasive fungal infections (1)
- Ionisation energy loss (1)
- Issue 96 (1)
- Jet Physics (1)
- Jet Substructure (1)
- KRAS (1)
- Lee-type (1)
- Local therapy (1)
- Lomentospora prolificans (1)
- Low & intermediate-energy accelerators (1)
- Lure sticks (1)
- MRI (1)
- MTOR inhibitor (1)
- Malaria (1)
- Material budget (1)
- Medicine (1)
- Metastasis-directed therapy (1)
- Mid-rapidity (1)
- MinION (1)
- Minimum Bias (1)
- Mitochondria (1)
- Monte Carlo (1)
- Morphometry (1)
- Multi-Parton Interactions (1)
- Multi-strange baryons (1)
- Multi-wire proportional drift chamber (1)
- Multiparametric MRI (1)
- NIRS (1)
- NRAS (1)
- NSE (1)
- NVBP (1)
- Nerve fibers (1)
- Neural network (1)
- Noninferiority (1)
- Noninvasive genetic sampling (1)
- Nuclear astrophysics (1)
- Nuclear modification factor (1)
- Nuclear physics of explosive environments (1)
- Nuclear reactions (1)
- Oligometastatic (1)
- Outcome (1)
- Ovarian cancer (1)
- PID prevalence (1)
- PSA screening (1)
- PSA-Screening (1)
- PYTHIA (1)
- Palacos reaction (1)
- Particle and Resonance Production (1)
- Pb–Pb (1)
- Pediatric patients (1)
- Percutaneous (1)
- Photon counting (1)
- Plasmodium (1)
- Pneumonia (1)
- Preclinical research (1)
- Prediction (1)
- Predictive markers (1)
- Preventive medicine (1)
- Production Cross Section (1)
- Properties of Hadrons (1)
- Prostata-specific antigen (1)
- Prostataspezifisches Antigen (1)
- Proteins (1)
- Proteomics (1)
- Proton (1)
- Proton–proton (1)
- Proton–proton collisions (1)
- Prävention (1)
- Psychiatry (1)
- Quantitative features (1)
- Quark Deconfinement (1)
- Quark Gluon Plasma (1)
- Quark Production (1)
- Quark gluon plasma (1)
- Quarkonium (1)
- Quinine (1)
- Radiative capture (1)
- Radical prostatectomy (1)
- Radiomics (1)
- Radiotherapy (1)
- Rapidity Range (1)
- Relativistic heavy ion physics (1)
- Relativistic heavy-ion collisions (1)
- Renal lesions (1)
- Renal replacement therapy (1)
- Research Infrastructure (1)
- Resolution Parameter (1)
- Rhabdomyoma (1)
- Risk factors (1)
- S100b (1)
- SARS-CoV-2 (1)
- SNORD95 (1)
- SR-BI (1)
- SVR (1)
- Scedosporium spp. (1)
- Seasonal variation (1)
- Semantics (1)
- Severe malaria (1)
- Shear viscosity (1)
- Single muons (1)
- Sociodemographic characteristics (1)
- Solar insolation (1)
- Statistical analysis (1)
- Stroke (1)
- Subependymal giant cell astrocytoma (1)
- Suchmaschine (1)
- Suicide (1)
- Sunlight (1)
- Surgery (1)
- Surgical oncology (1)
- Systematic Uncertainty (1)
- Systemic therapy (1)
- TACE (1)
- TILs (1)
- TR (1)
- TSC (1)
- TURP (1)
- Taxonomy (1)
- Thermal model (1)
- Thoracic trauma (1)
- Time Projection Chamber (1)
- Tinnitus (1)
- Tomography (1)
- Tracking (1)
- Transition radiation detector (1)
- Transverse momentum (1)
- Trigger (1)
- Urinary continence (1)
- Urinary incontinence (1)
- VISTA (1)
- Valvular cardiomyopathy (1)
- Vector Boson Production (1)
- Voriconazole (1)
- Vorsorgeuntersuchung (1)
- Xenon-based gas mixture (1)
- adverse events (1)
- algorithm (1)
- allogeneic stem cell transplant (1)
- angiography (1)
- antibiotic resistance (1)
- apex (1)
- assembly (1)
- atherosclerosis (1)
- biopsy cores (1)
- bladder neck stenosis (1)
- blastic plasmacytoid dendritic cell neoplasm (1)
- bloodstream infections (1)
- bundle (1)
- c-MET (1)
- cabozantinib (1)
- cardiac events (1)
- cardiac magnetic resonance (1)
- castration resistance (1)
- cell barrier integrity (1)
- cell lines (1)
- cetuximab (1)
- chemotherapy (1)
- clinical stage (1)
- complications (1)
- confirmatory factor analysis (1)
- coronary calcium (1)
- coronary computed-tomography angiography (CCTA) (1)
- coronary plaques (1)
- cuticular hydrocarbons (1)
- dE/dx (1)
- decision tree (1)
- delirium (1)
- desaturase (1)
- detector (1)
- direct-acting antivirals (1)
- dislocation (1)
- e-scooter (1)
- early tumor stages (1)
- electric scooter (1)
- elongase (1)
- embolization (1)
- endourology (1)
- experimental results (1)
- external fixation (1)
- fixed-links modeling (1)
- fluid intelligence (1)
- formalin-fixed and paraffin-embedded tissue (FFPE) (1)
- formicine (1)
- fracture (1)
- head-and-neck cancer (1)
- heavy ion experiments (1)
- hemodynamic instability (1)
- hemorrhage (1)
- hepatic fibrosis (1)
- hepatic stellate cells (1)
- hepatitis C virus (1)
- hepatocellular cancer (1)
- histone deacetylase 5 (1)
- hospital length of stay (1)
- in vitro models (1)
- incontinence (1)
- insulin resistance (1)
- intensive care admission and mortality (1)
- lactate (1)
- laser-capture microdissection (1)
- leukemia (1)
- lung cancer (1)
- mTOR (1)
- mTOR inhibitor (1)
- management (1)
- marker (1)
- membranous urethra (1)
- metastasis (1)
- metastatic prostate cancer (1)
- miR-142-3p (1)
- miRNA (1)
- mid-term urinary continence (1)
- mortality (1)
- multiparametric magnetic resonance imaging (1)
- multiple trauma (1)
- mutually exclusive mutations (1)
- myocardial fibrosis (1)
- myocyte enhancer factor 2 (1)
- nerve-sparing surgery (1)
- next generation sequencing (1)
- nocardia (1)
- nocardiosis (1)
- oxLDL (1)
- p21-activated kinase 2 (1)
- pad-test (1)
- patient-reported outcomes (1)
- pediatric patients (1)
- pelvic injury (1)
- pelvic ring fracture (1)
- plasma (1)
- polytrauma (1)
- posttraumatic inflammation (1)
- prediction (1)
- prevention (1)
- primary immunodeficiency (PID) (1)
- prognosis (1)
- prostaglandin E2 (1)
- protein kinase D (1)
- proteomics (1)
- pulmonary nocardiosis (1)
- quantitative mass spectrometry (1)
- quark gluon plasma (1)
- re-irradiation (1)
- recurrent mutations (1)
- registry for primary immunodeficiency (1)
- resistant cell lines (1)
- risk group (1)
- risk prediction (1)
- scar (1)
- serum (1)
- solid tumors (1)
- sorafenib (1)
- spectra (1)
- spike-in SILAC (1)
- spine (1)
- squamous cell carcinoma (1)
- stage migration (1)
- steatosis (1)
- stroke (1)
- surgery (1)
- survival (1)
- tivantinib (1)
- traffic accident (1)
- transportation (1)
- traumatic brain injury (1)
- traumatic brain injury (TBI) (1)
- traumaticbraininjury(TBI) (1)
- treatment (1)
- urinary incontinence (1)
- vertebroplasty (1)
- working memory capacity (1)
- x-ray techniques (1)
- Öffentlichkeit (1)
- √sN N = 2.76 TeV (1)
- fibrogenesis (1)
Institute
The success of social insects is largely intertwined with their highly advanced chemical communication system that facilitates recognition and discrimination of species and nest-mates, recruitment, and division of labor. Hydrocarbons, which cover the cuticle of insects, not only serve as waterproofing agents but also constitute a major component of this communication system. Two cryptic Crematogaster species, which share their nest with Camponotus ants, show striking diversity in their cuticular hydrocarbon (CHC) profile. This mutualistic system therefore offers a great opportunity to study the genetic basis of CHC divergence between sister species. As a basis for further genome-wide studies high-quality genomes are needed. Here, we present the annotated draft genome for Crematogaster levior A. By combining the three most commonly used sequencing techniques—Illumina, PacBio, and Oxford Nanopore—we constructed a high-quality de novo ant genome. We show that even low coverage of long reads can add significantly to overall genome contiguity. Annotation of desaturase and elongase genes, which play a role in CHC biosynthesis revealed one of the largest repertoires in ants and a higher number of desaturases in general than in other Hymenoptera. This may provide a mechanistic explanation for the high diversity observed in C. levior CHC profiles.
Myocardial fibrosis and inflammation by CMR predict cardiovascular outcome in people living with HIV
(2021)
Objectives_: The goal of this study was to examine prognostic relationships between cardiac imaging measures and cardiovascular outcome in people living with human immunodeficiency virus (HIV) (PLWH) on highly active antiretroviral therapy (HAART).
Background: PLWH have a higher prevalence of cardiovascular disease and heart failure (HF) compared with the noninfected population. The pathophysiological drivers of myocardial dysfunction and worse cardiovascular outcome in HIV remain poorly understood.
Methods: This prospective observational longitudinal study included consecutive PLWH on long-term HAART undergoing cardiac magnetic resonance (CMR) examination for assessment of myocardial volumes and function, T1 and T2 mapping, perfusion, and scar. Time-to-event analysis was performed from the index CMR examination to the first single event per patient. The primary endpoint was an adjudicated adverse cardiovascular event (cardiovascular mortality, nonfatal acute coronary syndrome, an appropriate device discharge, or a documented HF hospitalization).
Results: A total of 156 participants (62% male; age [median, interquartile range]: 50 years [42 to 57 years]) were included. During a median follow-up of 13 months (9 to 19 months), 24 events were observed (4 HF deaths, 1 sudden cardiac death, 2 nonfatal acute myocardial infarction, 1 appropriate device discharge, and 16 HF hospitalizations). Patients with events had higher native T1 (median [interquartile range]: 1,149 ms [1,115 to 1,163 ms] vs. 1,110 ms [1,075 to 1,138 ms]); native T2 (40 ms [38 to 41 ms] vs. 37 ms [36 to 39 ms]); left ventricular (LV) mass index (65 g/m2 [49 to 77 g/m2] vs. 57 g/m2 [49 to 64 g/m2]), and N-terminal pro–B-type natriuretic peptide (109 pg/l [25 to 337 pg/l] vs. 48 pg/l [23 to 82 pg/l]) (all p < 0.05). In multivariable analyses, native T1 was independently predictive of adverse events (chi-square test, 15.9; p < 0.001; native T1 [10 ms] hazard ratio [95% confidence interval]: 1.20 [1.08 to 1.33]; p = 0.001), followed by a model that also included LV mass (chi-square test, 17.1; p < 0.001). Traditional cardiovascular risk scores were not predictive of the adverse events.
Conclusions: Our findings reveal important prognostic associations of diffuse myocardial fibrosis and LV remodeling in PLWH. These results may support development of personalized approaches to screening and early intervention to reduce the burden of HF in PLWH (International T1 Multicenter Outcome Study; NCT03749343).
Background: Surgical complications are associated with a significant burden to patients and hospitals and are increasingly discussed in recent literature. This cohort study reviewed surgery-related complications in a Level I trauma center. The effect of a complication avoidance care bundle on the rate of surgical complications was analyzed. Methods: All complications (surgical and nonsurgical) that occur in our trauma department are prospectively captured using a standardized documentation form and are discussed and analyzed in a weekly trauma Morbidity and Mortality (M&M) conference. Surgical complication rates are calculated using the annual surgical procedure numbers. Based on discussions in the M&M conference, a complication avoidance care bundle consisting of five measures was established: (1) Improving team situational awareness; (2) reducing operating room traffic by staff members and limiting door-opening events; (3) preoperative screening for infectious foci; (4) adapted preoperative antibiotic prophylaxis in anatomic regions with a high risk of infectious complications; and (5) use of iodine-impregnated adhesive drape. Results: The number of surgical procedures steadily increased over the study years, from 3587 in 2015 to 3962 in 2019 (an increase of 10.5%). Within this 5-year study period, the overall rate of surgical complications was 0.8%. Surgical site infections were the most frequently found complications (n = 40, 24.8% of all surgical complications), followed by screw malposition (n = 20, 12.4%), postoperative dislocations of arthroplasties (n = 18, 11.2%), and suboptimal fracture reduction (n = 18, 11.2%). Following implementation of the complication avoidance care bundle, the overall rate of surgical complications significantly decreased, from 1.14% in the year 2016 to 0.56% in the study year 2019, which represents a reduction of 51% within a 3-year time period. Conclusions: A multimodal strategy targeted at reducing the surgical complication rate can be successfully established based on a transparent discussion of adverse surgical outcomes. The combination of the different preventive measures was associated with reducing the overall complication rate by half within a 3-year time period.
Treatment options of locoregional recurrent head and neck squamous cell cancer (HNSCC) include both local strategies as surgery or re-radiotherapy and systemic therapy. In this prospective, multi-center, non-interventional study, patients were treated either with platinum-based chemotherapy and cetuximab (CT + Cet) or re-radiotherapy and cetuximab (RT + Cet). In the current analysis, progression-free survival (PFS) and overall survival (OS) were compared in patients with locoregional recurrence. Four hundred seventy patients were registered in 97 German centers. After exclusion of patients with distant metastases, a cohort of 192 patients was analyzed (129 CT + Cet, 63 RT + Cet). Radiotherapy was delivered as re-irradiation to 70% of the patients. The mean radiation dose was 51.8 Gy, whereas a radiation dose of ≥60 Gy was delivered in 33% of the patients. Chemotherapy mainly consisted of cisplatin/5-flurouracil (40%) or carboplatin/5-flurouracil (29%). The median PFS was 9.2 months in the RT + Cet group versus 5.1 months in the CT + Cet group (hazard ratio for disease progression or death, 0.40, 95% CI, 0.27–0.57, p < 0.0001). Median OS was 12.8 months in the RT + Cet group versus 7.9 months in the CT + Cet group (hazard ratio for death, 0.50, 95% CI, 0.33–0.75, p = 0.0008). In conclusion, radiotherapy combined with cetuximab improved survival compared to chemotherapy combined with cetuximab in locally recurrent HNSCC.
Background. Transcatheter aortic valve implantation (TAVI) is currently recommended for patients with severe aortic stenosis at intermediate or high surgical risk. The decision process during TAVI evaluation includes a thorough benefit-risk assessment, and knowledge about long-term benefits and outcomes may improve patients’ expectation management. Objective. To evaluate patients’ perceived health status and self-reported long-term outcome more than 5 years after TAVI. Methods and Results. Demographic and procedure data were obtained from all patients treated with TAVI at our institution from 2006 to 2012. A cross-sectional survey was conducted on the patients alive, measuring health status, including the EQ-5D-5L questionnaire, and clinical outcomes. 103 patients (22.8%) were alive at a median follow-up period of 7 years (5.4–9.8). 99 (96%) of the 103 patients were included in the final analysis. The mean age at follow-up was 86.5 years ± 8.0 years, and 56.6% were female. Almost all patients (93.9%) described an improvement of their quality of life after receiving TAVI. At late follow-up, the mean utility index and EQ-VAS score were 0.80 ± 0.20 and 58.49 ± 11.49, respectively. Mobility was found to be the most frequently reported limitation (85.4%), while anxiety/depression was the least frequently reported limitation (19.8%). With respect to functional class, 64.7% were in New York Heart Association (NYHA) class III or IV, compared to 67.0% prior to TAVI (p = 0.51). Self-reported long-term outcomes revealed mainly low long-term complication rates. 74 total hospitalizations were reported after TAVI, and among those 43% for cardiovascular reasons. Within cardiovascular rehospitalizations, new pacemaker implantations were the most frequently reported (18.9%), followed by cardiac decompensation and coronary heart disease (15.6%). Conclusion. The majority of the patients described an improvement of health status after TAVI. More than five years after TAVI, the patients’ perceived health status was satisfactory, and the incidence of clinical events and hospitalizations was very low.
Background: Cerebral O2 saturation (ScO2) reflects cerebral perfusion and can be measured noninvasively by near-infrared spectroscopy (NIRS). Objectives: In this pilot study, we describe the dynamics of ScO2 during TAVI in nonventilated patients and its impact on procedural outcome. Methods and Results: We measured ScO2 of both frontal lobes continuously by NIRS in 50 consecutive analgo-sedated patients undergoing transfemoral TAVI (female 58%, mean age 80.8 years). Compared to baseline ScO2 dropped significantly during RVP (59.3% vs. 53.9%, p < .01). Five minutes after RVP ScO2 values normalized (post RVP 62.6% vs. 53.9% during RVP, p < .01; pre 61.6% vs. post RVP 62.6%, p = .53). Patients with an intraprocedural pathological ScO2 decline of >20% (n = 13) had higher EuroSCORE II (3.42% vs. 5.7%, p = .020) and experienced more often delirium (24% vs. 62%, p = .015) and stroke (0% vs. 23%, p < .01) after TAVI. Multivariable logistic regression revealed higher age and large ScO2 drops as independent risk factors for delirium. Conclusions: During RVP ScO2 significantly declined compared to baseline. A ScO2 decline of >20% is associated with a higher incidence of delirium and stroke and a valid cut-off value to screen for these complications. NIRS measurement during TAVI procedure may be an easy to implement diagnostic tool to detect patients at high risks for cerebrovascular complications and delirium.
In-depth analyses of cancer cell proteomes are needed to elucidate oncogenic pathomechanisms, as well as to identify potential drug targets and diagnostic biomarkers. However, methods for quantitative proteomic characterization of patient-derived tumors and in particular their cellular subpopulations are largely lacking. Here we describe an experimental set-up that allows quantitative analysis of proteomes of cancer cell subpopulations derived from either liquid or solid tumors. This is achieved by combining cellular enrichment strategies with quantitative Super-SILAC-based mass spectrometry followed by bioinformatic data analysis. To enrich specific cellular subsets, liquid tumors are first immunophenotyped by flow cytometry followed by FACS-sorting; for solid tumors, laser-capture microdissection is used to purify specific cellular subpopulations. In a second step, proteins are extracted from the purified cells and subsequently combined with a tumor-specific, SILAC-labeled spike-in standard that enables protein quantification. The resulting protein mixture is subjected to either gel electrophoresis or Filter Aided Sample Preparation (FASP) followed by tryptic digestion. Finally, tryptic peptides are analyzed using a hybrid quadrupole-orbitrap mass spectrometer, and the data obtained are processed with bioinformatic software suites including MaxQuant. By means of the workflow presented here, up to 8,000 proteins can be identified and quantified in patient-derived samples, and the resulting protein expression profiles can be compared among patients to identify diagnostic proteomic signatures or potential drug targets.
Malignant germ cell tumors (GCT) are the most common malignant tumors in young men between 18 and 40 years. The correct identification of histological subtypes, in difficult cases supported by immunohistochemistry, is essential for therapeutic management. Furthermore, biomarkers may help to understand pathophysiological processes in these tumor types. Two GCT cell lines, TCam-2 with seminoma-like characteristics, and NTERA-2, an embryonal carcinoma-like cell line, were compared by a quantitative proteomic approach using high-resolution mass spectrometry (MS) in combination with stable isotope labelling by amino acid in cell culture (SILAC). We were able to identify 4856 proteins and quantify the expression of 3936. 347 were significantly differentially expressed between the two cell lines. For further validation, CD81, CBX-3, PHF6, and ENSA were analyzed by western blot analysis. The results confirmed the MS results. Immunohistochemical analysis on 59 formalin-fixed and paraffin-embedded (FFPE) normal and GCT tissue samples (normal testis, GCNIS, seminomas, and embryonal carcinomas) of these proteins demonstrated the ability to distinguish different GCT subtypes, especially seminomas and embryonal carcinomas. In addition, siRNA-mediated knockdown of these proteins resulted in an antiproliferative effect in TCam-2, NTERA-2, and an additional embryonal carcinoma-like cell line, NCCIT. In summary, this study represents a proteomic resource for the discrimination of malignant germ cell tumor subtypes and the observed antiproliferative effect after knockdown of selected proteins paves the way for the identification of new potential drug targets.
The transcription factor Meis1 drives myeloid leukemogenesis in the context of Hox gene overexpression but is currently considered undruggable. We therefore investigated whether myeloid progenitor cells transformed by Hoxa9 and Meis1 become addicted to targetable signaling pathways. A comprehensive (phospho)proteomic analysis revealed that Meis1 increased Syk protein expression and activity. Syk upregulation occurs through a Meis1-dependent feedback loop. By dissecting this loop, we show that Syk is a direct target of miR-146a, whose expression is indirectly regulated by Meis1 through the transcription factor PU.1. In the context of Hoxa9 overexpression, Syk signaling induces Meis1, recapitulating several leukemogenic features of Hoxa9/Meis1-driven leukemia. Finally, Syk inhibition disrupts the identified regulatory loop, prolonging survival of mice with Hoxa9/Meis1-driven leukemia.
The endoplasmic reticulum–mitochondria encounter structure (ERMES) connects the mitochondrial outer membrane with the ER. Multiple functions have been linked to ERMES, including maintenance of mitochondrial morphology, protein assembly and phospholipid homeostasis. Since the mitochondrial distribution and morphology protein Mdm10 is present in both ERMES and the mitochondrial sorting and assembly machinery (SAM), it is unknown how the ERMES functions are connected on a molecular level. Here we report that conserved surface areas on opposite sides of the Mdm10 β-barrel interact with SAM and ERMES, respectively. We generated point mutants to separate protein assembly (SAM) from morphology and phospholipid homeostasis (ERMES). Our study reveals that the β-barrel channel of Mdm10 serves different functions. Mdm10 promotes the biogenesis of α-helical and β-barrel proteins at SAM and functions as integral membrane anchor of ERMES, demonstrating that SAM-mediated protein assembly is distinct from ER-mitochondria contact sites.
hintergrund: Männer in Deutschland sterben früher als Frauen und nehmen weniger häufig Krebsvorsorgeuntersuchungen wahr.
Fragestellung: Ziel war die prospektive Evaluation einer „Movember-Gesundheitsinitiative“ am Universitätsklinikum Frankfurt (UKF) im November 2019.
Methoden: Im Rahmen der „Movember-Gesundheitsinitiative“ wurde allen männlichen Mitarbeitern des UKF ab dem 45. Lebensjahr und bei erstgradiger familiärer Vorbelastung eines Prostatakarzinoms ab dem 40. Lebensjahr im November 2019 gemäß S3-Leitlinien der Deutschen Gesellschaft für Urologie (DGU) eine Prostatakarzinom-Vorsorgeuntersuchung angeboten.
Ergebnisse: Insgesamt nahmen 14,4 % der Mitarbeiter teil. Eine familiäre Vorbelastung gaben insgesamt 14,0 % Teilnehmer an. Das mediane Alter betrug 54 Jahre. Der mediane PSA(prostataspezifisches Antigen)-Wert lag bei 0,9 ng/ml, der mediane PSA-Quotient bei 30 %. Bei 5 % (n = 6) zeigte sich ein suspekter Tastbefund in der DRU (digital-rektale Untersuchung). Nach Altersstratifizierung (≤ 50 vs. > 50 Lebensjahre) zeigten sich signifikante Unterschiede im medianen PSA-Wert (0,7 ng/ml vs. 1,0 ng/ml, p < 0,01) und der bereits zuvor durchgeführten urologischen Vorsorge (12,1 vs. 42,0 %, p < 0,01). Vier Teilnehmer (3,3 %) zeigten erhöhte Gesamt-PSA-Werte. Bei 32,2 % der Teilnehmer zeigte sich mindestens ein kontrollbedürftiger Befund. Insgesamt wurden 6 Prostatabiopsien durchgeführt. Hierbei zeigte sich in einem Fall ein intermediate-risk Prostatakarzinom (Gleason 3 + 4, pT3a, pPn1, pNx, R0).
Schlussfolgerungung: Im Rahmen der UKF-Movember-Gesundheitsinitiative 2019 konnten durch ein Vorsorgeangebot 121 Männer für eine Prostatakrebs-Vorsorge inklusive PSA-Testung gewonnen werden. Auffällige/kontrollbedürftige Befunde zeigten sich bei 32,2 %. Bei einem Mitarbeiter wurde ein therapiebedürftiges Prostatakarzinom entdeckt und therapiert.
Background: The potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC. Methods: The study is an open-labelled, randomised, RCT comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing LT for HCC. Patients with a histologically confirmed HCC diagnosis are randomised into 2 groups within 4-6 weeks after LT; one arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol and the second arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol for the first 4-6 weeks, at which time sirolimus is initiated. A 3-year recruitment phase is planned with a 5-year follow-up, testing HCC-free survival as the primary endpoint. Our hypothesis is that sirolimus use in the second arm of the study will improve HCC-free survival. The study is a non-commercial investigator-initiated trial (IIT) sponsored by the University Hospital Regensburg and is endorsed by the European Liver and Intestine Transplant Association; 13 countries within Europe, Canada and Australia are participating. Discussion: If our hypothesis is correct that mTOR inhibition can reduce HCC tumour growth while simultaneously providing immunosuppression to protect the liver allograft from rejection, patients should experience less post-transplant problems with HCC recurrence, and therefore could expect a longer and better quality of life. A positive outcome will likely change the standard of posttransplant immunosuppressive care for LT patients with HCC. (trial registered at www.clinicaltrials.gov: NCT00355862) (EudraCT Number: 2005-005362-36)
Creatinine and proteinuria are used to monitor kidney transplant patients. However, renal biopsies are needed to diagnose renal graft rejection. Here, we assessed whether the quantification of different urinary cells would allow non-invasive detection of rejection. Urinary cell numbers of CD4+ and CD8+ T cells, monocytes/macrophages, tubular epithelial cells (TEC), and podocalyxin(PDX)-positive cells were determined using flow cytometry and were compared to biopsy results. Urine samples of 63 renal transplant patients were analyzed. Patients with transplant rejection had higher amounts of urinary T cells than controls; however, patients who showed worsening graft function without rejection had similar numbers of T cells. T cells correlated with histological findings (interstitial inflammation p = 0.0005, r = 0.70; tubulitis p = 0.006, r = 0.58). Combining the amount of urinary T cells and TEC, or T cells and PDX+ cells, yielded a significant segregation of patients with rejection from patients without rejection (all p < 0.01, area under the curve 0.89–0.91). Urinary cell populations analyzed by flow cytometry have the potential to introduce new monitoring methods for kidney transplant patients. The combination of urinary T cells, TEC, and PDX-positive cells may allow non-invasive detection of transplant rejection.
This demo abstract describes the SmartWeb Ontology-based Information Extraction System (SOBIE). A key feature of SOBIE is that all information is extracted and stored with respect to the SmartWeb ontology. In this way, other components of the systems, which use the same ontology, can access this information in a straightforward way. We will show how information extracted by SOBIE is visualized within its original context, thus enhancing the browsing experience of the end user.
Background: Cerebral oxygen saturation (ScO2) can be measured non-invasively by near-infrared spectroscopy (NIRS) and correlates with cerebral perfusion. We investigated cerebral saturation during transfemoral transcatheter aortic valve implantation (TAVI) and its impact on outcome.
Methods and results: Cerebral oxygenation was measured continuously by NIRS in 173 analgo-sedated patients during transfemoral TAVI (female 47%, mean age 81 years) with self-expanding (39%) and balloon-expanding valves (61%). We investigated the periprocedural dynamics of cerebral oxygenation. Mean ScO2 at baseline without oxygen supply was 60%. During rapid ventricular pacing, ScO2 dropped significantly (before 64% vs. after 55%, p < 0.001). ScO2 at baseline correlated positively with baseline left-ventricular ejection fraction (0.230, p < 0.006) and hemoglobin (0.327, p < 0.001), and inversely with EuroSCORE-II ( − 0.285, p < 0.001) and length of in-hospital stay ( − 0.229, p < 0.01). Patients with ScO2 < 56% despite oxygen supply at baseline had impaired 1 year survival (log-rank test p < 0.01) and prolonged in-hospital stay (p = 0.03). Furthermore, baseline ScO2 was found to be a predictor for 1 year survival independent of age and sex (multivariable adjusted Cox regression, p = 0.020, hazard ratio (HR 0.94, 95% CI 0.90–0.99) and independent of overall perioperative risk estimated by EuroSCORE-II and hemoglobin (p = 0.03, HR 0.95, 95% CI 0.91–0.99).
Conclusions: Low baseline ScO2 not responding to oxygen supply might act as a surrogate for impaired cardiopulmonary function and is associated with worse 1 year survival and prolonged in-hospital stay after transfemoral TAVI. ScO2 monitoring is an easy to implement diagnostic tool to screen patients at risk with a potential preserved recovery and worse outcome after TAVI.
Background: To determine the correlation between urine loss in PAD-test after catheter removal, and early urinary continence (UC) in RP treated patients. Methods: Urine loss was measured by using a standardized, validated PAD-test within 24 h after removal of the transurethral catheter, and was grouped as a loss of <1, 1–10, 11–50, and >50 g of urine, respectively. Early UC (median: 3 months) was defined as the usage of no or one safety-pad. Uni- and multivariable logistic regression models tested the correlation between PAD-test results and early UC. Covariates consisted of age, BMI, nerve-sparing approach, prostate volume, and extraprostatic extension of tumor. Results: From 01/2018 to 03/2021, 100 patients undergoing RP with data available for a PAD-test and early UC were retrospectively identified. Ultimately, 24%, 47%, 15%, and 14% of patients had a loss of urine <1 g, 1–10 g, 11–50 g, and >50 g in PAD-test, respectively. Additionally, 59% of patients reported to be continent. In multivariable logistic regression models, urine loss in PAD-test predicted early UC (OR: 0.21 vs. 0.09 vs. 0.03; for urine loss 1–10 g vs. 11–50 g vs. >50 g, Ref: <1 g; all p < 0.05). Conclusions: Urine loss after catheter removal strongly correlated with early continence as well as a severity in urinary incontinence.
Background: We aimed to determine the concordance between the radiologic stage (rT), using multiparametric magnetic resonance imaging (mpMRI), and pathologic stage (pT) in patients with high-risk prostate cancer and its influence on nerve-sparing surgery compared to the use of the intraoperative frozen section technique (IFST). Methods: The concordance between rT and pT and the rates of nerve-sparing surgery and positive surgical margin were assessed for patients with high-risk prostate cancer who underwent radical prostatectomy. Results: The concordance between the rT and pT stages was shown in 66.4% (n = 77) of patients with clinical high-risk prostate cancer. The detection of patients with extraprostatic disease (≥pT3) by preoperative mpMRI showed a sensitivity, negative predictive value and accuracy of 65.1%, 51.7% and 67.5%. In addition to the suspicion of extraprostatic disease in mpMRI (≥rT3), 84.5% (n = 56) of patients with ≥rT3 underwent primary nerve-sparing surgery with IFST, resulting in 94.7% (n = 54) of men with at least unilateral nerve-sparing surgery after secondary resection with a positive surgical margin rate related to an IFST of 1.8% (n = 1). Conclusion: Patients with rT3 should not be immediately excluded from nerve-sparing surgery, as by using IFST some of these patients can safely undergo nerve-sparing surgery.
Blood-pressure-lowering drugs are proposed to foster SARS-CoV-2 infection by pharmacological upregulation of angiotensin-converting enzyme 2 (ACE2), the binding partner of the virus spike (S) protein, located on the surface of the host cells. Conversely, it is postulated that angiotensin–renin system antagonists may prevent lung damage caused by SARS-CoV-2 infection, by reducing angiotensin II levels, which can induce permeability of lung endothelial barrier via its interaction with the AT1 receptor (AT1R). Methods: We have investigated the influence of the ACE inhibitors (lisinopril, captopril) and the AT1 antagonists (telmisartan, olmesartan) on the level of ACE2 mRNA and protein expression as well as their influence on the cytopathic effect of SARS-CoV-2 and on the cell barrier integrity in a Caco-2 cell model. Results: The drugs revealed no effect on ACE2 mRNA and protein expression. ACE inhibitors and AT1R antagonist olmesartan did not influence the infection rate of SARS-CoV-2 and were unable to prevent the SARS-CoV-2-induced cell barrier disturbance. A concentration of 25 µg/mL telmisartan significantly reduced the virus replication rate. Conclusion: ACE inhibitors and AT1R antagonist showed neither beneficial nor detrimental effects on SARS-CoV-2-infection and cell barrier integrity in vitro at pharmacologically relevant concentrations.
Objectives: Current knowledge on infections caused by Scedosporium spp. and Lomentospora prolificans in children is scarce. We therefore aim to provide an overview of risk groups, clinical manifestation and treatment strategies of these infections.
Methods: Pediatric patients (age ≤18 years) with proven/probable Scedosporium spp. or L. prolificans infection were identified in PubMed and the FungiScope® registry. Data on diagnosis, treatment and outcome were collected.
Results: Fifty-five children (median age 9 years [IQR: 5–14]) with invasive Scedosporium spp. (n = 33) or L. prolificans (n = 22) infection were identified between 1990 and 2019. Malignancy, trauma and near drowning were the most common risk factors. Infections were frequently disseminated. Most patients received systemic antifungal therapy, mainly voriconazole and amphotericin B, plus surgical treatment.
Overall, day 42 mortality was 31%, higher for L. prolificans (50%) compared to Scedosporium spp. (18%). L. prolificans infection was associated with a shorter median survival time compared to Scedosporium spp. (6 days [IQR: 3–28] versus 61 days [IQR: 16–148]). Treatment for malignancy and severe disseminated infection were associated with particularly poor outcome (HR 8.33 [95% CI 1.35–51.40] and HR 6.12 [95% CI 1.52–24.66], respectively). Voriconazole use at any time and surgery for antifungal treatment were associated with improved clinical outcome (HR 0.33 [95% CI 0.11–0.99] and HR 0.09 [95% CI 0.02–0.40], respectively).
Conclusions: Scedosporium spp. and L. prolificans infections in children are associated with high mortality despite comprehensive antifungal therapy. Voriconazole usage and surgical intervention are associated with successful outcome.
Background: The aim of this study was to identify pre-operative parameters able to predict length of stay (LoS) based on clinical data and patient-reported outcome measures (PROMs) from a scorecard database in patients with significant aortic stenosis who underwent TAVI (transfemoral aortic valve implantation). Methods: 302 participants (51.7% males, age range 78.2–84.2 years.) were prospectively recruited. After computing the median LoS value (=6 days, range = 5–8 days), we implemented a decision tree algorithm by setting dichotomized values at median LoS as the dependent variable and assessed baseline clinical variables and PROMs (Clinical Frailty Scale (CFS), EuroQol-5 Dimension-5 Levels (EQ-5D) and Kansas City Cardiomyopathy Questionnaire (KCCQ)) as potential predictors. Results: Among clinical parameters, only peripheral arterial disease (p = 0.029, HR = 1.826) and glomerular filtration rate (GFR, cut-off < 33 mL/min/1.73 m2, p = 0.003, HR = 2.252) were predictive of LoS. Additionally, two PROMs (CFS; cut-off = 3, p < 0.001, HR = 1.324 and KCCQ; cut-off = 30, p = 0.003, HR = 2.274) were strong predictors. Further, a risk score for LoS (RS_LoS) was calculated based on these predictors. Patients with RS_LoS = 0 had a median LoS of 5 days; patients RS_LoS ≥ 3 had a median LoS of 8 days. Conclusions: based on the pre-operative values of the above four predictors, a personalized prediction of LoS after TAVI can be achieved.