Vena contracta area for severity grading in functional and degenerative mitral regurgitation: a transoesophageal 3D colour Doppler analysis in 500 patients.

Aims: Vena contracta area (VCA3D), derived by 3D colour Doppler echocardiography, has already been validated against cardiac magnetic resonance imaging, but the number of clinical studies to define cut-off values for grading of mitral regurgitation (MR) is limited. Aim of the study was to assess VCA3D in a large population of patients with functional (FMR) and degenerative MR (DMR).

Methods And Results: Transoesophageal echocardiography was performed in 500 patients with MR.

Difference optimization: Automatic correction of relative frequency and phase for mean non-edited and edited GABA H MEGA-PRESS spectra.

Phase and frequency corrections of magnetic resonance spectroscopic data are of major importance to obtain reliable and unambiguous metabolite estimates as validated in recent research for single-shot scans with the same spectral fingerprint. However, when using the J-difference editing technique H MEGA-PRESS, misalignment between mean edited (ON‾) and non-edited (OFF‾) spectra that may remain even after correction of the corresponding individual single-shot scans results in subtraction artefacts compromising reliable GABA quantitation. We present a fully automatic routine that iteratively optimizes simultaneously relative frequencies and phases between the mean ON‾ and OFF‾H MEGA-PRESS spectra while minimizing the sum of the magnitude of the difference spectrum (L norm).

Fatal abdominal injuries in a bicycle-pedestrian collision - Reconstruction using multibody simulation.

Fatal bicycle-pedestrian collisions do not occur frequently and thus are rarely reported in literature. Pedestrians in bicycle-pedestrian accidents often sustain severe craniocerebral injuries caused by a collision induced fall with head impact on the road surface. We describe a case where a pedestrian crossing a road was hit by a bicycle.

Changes of deep gray matter magnetic susceptibility over 2 years in multiple sclerosis and healthy control brain.

In multiple sclerosis, pathological changes of both tissue iron and myelin occur, yet these factors have not been characterized in a longitudinal fashion using the novel iron- and myelin-sensitive quantitative susceptibility mapping (QSM) MRI technique. We investigated disease-relevant tissue changes associated with myelin loss and iron accumulation in multiple sclerosis deep gray matter (DGM) over two years. One-hundred twenty (120) multiple sclerosis patients and 40 age- and sex-matched healthy controls were included in this prospective study.

Cardiac 4D phase-contrast CMR at 9.4 T using self-gated ultra-short echo time (UTE) imaging.

Background: Time resolved 4D phase contrast (PC) cardiovascular magnetic resonance (CMR) in mice is challenging due to long scan times, small animal ECG-gating and the rapid blood flow and cardiac motion of small rodents. To overcome several of these technical challenges we implemented a retrospectively self-gated 4D PC radial ultra-short echo-time (UTE) acquisition scheme and assessed its performance in healthy mice by comparing the results with those obtained with an ECG-triggered 4D PC fast low angle shot (FLASH) sequence.

Methods: Cardiac 4D PC CMR images were acquired at 9.

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.

Nanoparticle-based hyperthermia distinctly impacts production of ROS, expression of Ki-67, TOP2A, and TPX2, and induction of apoptosis in pancreatic cancer.

So far, the therapeutic outcome of hyperthermia has shown heterogeneous responses depending on how thermal stress is applied. We studied whether extrinsic heating (EH, hot air) and intrinsic heating (magnetic heating [MH] mediated by nanoparticles) induce distinct effects on pancreatic cancer cells (PANC-1 and BxPC-3 cells). The impact of MH (100 µg magnetic nanoparticles [MNP]/mL; H=23.

An improved FSL-FIRST pipeline for subcortical gray matter segmentation to study abnormal brain anatomy using quantitative susceptibility mapping (QSM).

Accurate and robust segmentation of subcortical gray matter (SGM) nuclei is required in many neuroimaging applications. FMRIB's Integrated Registration and Segmentation Tool (FIRST) is one of the most popular software tools for automated subcortical segmentation based on T-weighted (T1w) images. In this work, we demonstrate that FIRST tends to produce inaccurate SGM segmentation results in the case of abnormal brain anatomy, such as present in atrophied brains, due to a poor spatial match of the subcortical structures with the training data in the MNI space as well as due to insufficient contrast of SGM structures on T1w images.

Enrichment of putative PAX8 target genes at serous epithelial ovarian cancer susceptibility loci.

Background: Genome-wide association studies (GWAS) have identified 18 loci associated with serous ovarian cancer (SOC) susceptibility but the biological mechanisms driving these findings remain poorly characterised. Germline cancer risk loci may be enriched for target genes of transcription factors (TFs) critical to somatic tumorigenesis.

Methods: All 615 TF-target sets from the Molecular Signatures Database were evaluated using gene set enrichment analysis (GSEA) and three GWAS for SOC risk: discovery (2196 cases/4396 controls), replication (7035 cases/21 693 controls; independent from discovery), and combined (9627 cases/30 845 controls; including additional individuals).

Automatic CT-based finite element model generation for temperature-based death time estimation: feasibility study and sensitivity analysis.

Temperature-based death time estimation is based either on simple phenomenological models of corpse cooling or on detailed physical heat transfer models. The latter are much more complex but allow a higher accuracy of death time estimation, as in principle, all relevant cooling mechanisms can be taken into account.Here, a complete workflow for finite element-based cooling simulation is presented.

The Processing of Somatosensory Information Shifts from an Early Parallel into a Serial Processing Mode: A Combined fMRI/MEG Study.

The question regarding whether somatosensory inputs are processed in parallel or in series has not been clearly answered. Several studies that have applied dynamic causal modeling (DCM) to fMRI data have arrived at seemingly divergent conclusions. However, these divergent results could be explained by the hypothesis that the processing route of somatosensory information changes with time.

Metacarpal bone loss in patients with rheumatoid arthritis estimated by a new Digital X-ray Radiogrammetry method - initial results.

Background: The Digital X-ray Radiogrammetry (DXR) method measures the cortical bone thickness in the shafts of the metacarpals and has demonstrated its relevance in the assessment of hand bone loss caused by rheumatoid arthritis (RA). The aim of this study was to validate a novel approach of the DXR method in comparison with the original version considering patients with RA.

Method: The study includes 49 patients with verified RA.

Susceptibility Sensitive Magnetic Resonance Imaging Displays Pallidofugal and Striatonigral Fiber Tracts.

Background: The pallidofugal and striatonigral fiber tracts form a functional part of the basal ganglionic neuronal networks. For deep brain stimulation, a surgical procedure applied in the treatment of Parkinson disease and dystonia, precise localization of pallidofugal pathways may be of particular clinical relevance for correct electrode positioning.

Objective: To investigate whether the pallidofugal and striatonigral pathways can be visualized with magnetic resonance imaging in vivo by exploiting their intrinsic magnetic susceptibility.

Platinum(ii) O,S complexes as potential metallodrugs against Cisplatin resistance.

We report on platinum(ii) complexes with different cinnamic acid derivatives as ligands with cytotoxic activity against Cisplatin resistant ovarian cancer cell line subcultures of SKOV3 and A2780. A typical mechanism of action for platinum(ii) complexes as Cisplatin itself is binding to the DNA and inducing double-strand breaks. We examined the biological behavior of these potential drugs with 9-methylguanine using NMR spectroscopic methods and their DNA damage potential including γH2AX-foci analyses.

Peripheral nerve ultrasound scoring systems: benchmarking and comparative analysis.

Ultrasound of the nerves is an additive diagnostic tool to evaluate polyneuropathy. Recently, the need for standardized scoring systems has widely been discussed; different scores are described so far. Therefore, 327 patients with polyneuropathy were analyzed by ultrasound in our laboratory.

Vertigo and the processing of vestibular information: A review in the context of predictive coding.

This article investigates the processing of vestibular information by interpreting current experimental knowledge in the framework of predictive coding. We demonstrate that this theoretical framework give us insights into several important questions regarding specific properties of the vestibular system. Particularly, we discuss why the vestibular network is more spatially distributed than other sensory networks, why a mismatch in the vestibular system is more clinically disturbing than in other sensory systems, why the vestibular system is only marginally affected by most cerebral lesions, and whether there is a primary vestibular cortex.

Nonlinear Structured Illumination Using a Fluorescent Protein Activating at the Readout Wavelength.

Structured illumination microscopy (SIM) is a wide-field technique in fluorescence microscopy that provides fast data acquisition and two-fold resolution improvement beyond the Abbe limit. We observed a further resolution improvement using the nonlinear emission response of a fluorescent protein. We demonstrated a two-beam nonlinear structured illumination microscope by introducing only a minor change into the system used for linear SIM (LSIM).

Psoriatic arthritis is associated with bone loss of the metacarpals.

Background: BoneXpert (BX) is a newly developed medical device based on digital X-ray radiogrammetry to measure human cortical bone thickness. The aim of this study was to quantify cortical bone loss of the metacarpals in patients with psoriatic arthritis (PsA) and compare these findings with other radiological scoring methods.

Methods: The study includes 104 patients with verified PsA.

MK2/3 Are Pivotal for IL-33-Induced and Mast Cell-Dependent Leukocyte Recruitment and the Resulting Skin Inflammation.

The IL-1R family member IL-33R mediates Fcε-receptor-I (FcεRI)-independent activation of mast cells leading to NF-κB activation and consequently the production of cytokines. IL-33 also induces the activation of MAPKs, such as p38. We aimed to define the relevance of the p38-targets, the MAPK-activated protein kinases 2 and 3 (MK2 and MK3) in IL-33-induced signaling and the resulting mast cell effector functions in vitro and in vivo.

Dataset on FAP-induced emergence of spontaneous metastases and on the preparation of activatable FAP-targeting immunoliposomes to detect the metastases.

The underlying data demonstrates that fibroblast activation protein (FAP) paves the way for fibrosarcoma cells, which require the proteolysis of the extracellular matrix (ECM) and basement membranes to intravasate from implanted subcutaneous primary tumors into blood vessels, be transported to distant organs where they extravasate from the blood vessels, reattach and proliferate to metastases. The data additionally shows that FAP, when overexpressed on fibrosarcoma cells induces their invasion and formation of spontaneous metastases in multiple organs, particularly after subcutaneous co-implantation of the FAP-expressing and wildtype fibrosarcoma. The raw and processed data presented herein is related to a research article entitled "Potential of activatable FAP-targeting immunoliposomes in intraoperative imaging of spontaneous metastases" (F.

Association of vitamin D levels and risk of ovarian cancer: a Mendelian randomization study.

Background: In vitro and observational epidemiological studies suggest that vitamin D may play a role in cancer prevention. However, the relationship between vitamin D and ovarian cancer is uncertain, with observational studies generating conflicting findings. A potential limitation of observational studies is inadequate control of confounding.

Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer.

Background: Regulatory T (Treg) cells, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and, thus, variants in genes encoding Treg cell immune molecules could be associated with ovarian cancer.

Methods: In a population of 15,596 epithelial ovarian cancer (EOC) cases and 23,236 controls, we measured genetic associations of 1,351 SNPs in Treg cell pathway genes with odds of ovarian cancer and tested pathway and gene-level associations, overall and by histotype, for the 25 genes, using the admixture likelihood (AML) method. The most significant single SNP associations were tested for correlation with expression levels in 44 ovarian cancer patients.

Quantitative Non-canonical Amino Acid Tagging (QuaNCAT) Proteomics Identifies Distinct Patterns of Protein Synthesis Rapidly Induced by Hypertrophic Agents in Cardiomyocytes, Revealing New Aspects of Metabolic Remodeling.

Cardiomyocytes undergo growth and remodeling in response to specific pathological or physiological conditions. In the former, myocardial growth is a risk factor for cardiac failure and faster protein synthesis is a major factor driving cardiomyocyte growth. Our goal was to quantify the rapid effects of different pro-hypertrophic stimuli on the synthesis of specific proteins in ARVC and to determine whether such effects are caused by alterations on mRNA abundance or the translation of specific mRNAs.

Overview of quantitative susceptibility mapping.

Magnetic susceptibility describes the magnetizability of a material to an applied magnetic field and represents an important parameter in the field of MRI. With the recently introduced method of quantitative susceptibility mapping (QSM) and its conceptual extension to susceptibility tensor imaging (STI), the non-invasive assessment of this important physical quantity has become possible with MRI. Both methods solve the ill-posed inverse problem to determine the magnetic susceptibility from local magnetic fields.

Unusual mode of protein binding by a cytotoxic π-arene ruthenium(ii) piano-stool compound containing an O,S-chelating ligand.

A new pseudo-octahedral π-arene ruthenium(ii) piano-stool compound, containing an O,S-bidentate ligand (compound 1) and showing significant cytotoxic activity in vitro, was synthesized and characterized. In solution stability and interaction with the model protein bovine pancreatic ribonuclease (RNase A) were investigated by using UV-Vis absorption spectroscopy. Its crystal structure and that of the adduct formed upon reaction with RNase A were obtained by X-ray crystallography.