Fetal whole-heart 4D imaging using motion-corrected multi-planar real-time MRI

Purpose: To develop a MRI acquisition and reconstruction framework for volumetric cine visualisation of the fetal heart and great vessels in the presence of maternal and fetal motion. Methods: Four-dimensional depiction was achieved using a highly-accelerated multi-planar real-time balanced steady state free precession acquisition combined with retrospective image-domain techniques for motion correction, cardiac synchronisation and outlier rejection. The framework was evaluated and optimised using a numerical phantom, and evaluated in a study of 20 mid- to late-gestational age human fetal subjects. Reconstructed cine volumes were evaluated by experienced cardiologists and compared with matched ultrasound. A preliminary assessment of flow-sensitive reconstruction using the velocity information encoded in the phase of dynamic images is included. Results: Reconstructed cine volumes could be visualised in any 2D plane without the need for highly-specific scan plane prescription prior to acquisition or for maternal breath hold to minimise motion. Reconstruction was fully automated aside from user-specified masks of the fetal heart and chest. The framework proved robust when applied to fetal data and simulations confirmed that spatial and temporal features could be reliably recovered. Expert evaluation suggested the reconstructed volumes can be used for comprehensive assessment of the fetal heart, either as an adjunct to ultrasound or in combination with other MRI techniques. Conclusion: The proposed methods show promise as a framework for motion-compensated 4D assessment of the fetal heart and great vessels

Fully automated planning for anatomical fetal brain MRI on 0.55T

Purpose: Widening the availability of fetal MRI with fully automatic real-time planning of radiological brain planes on 0.55T MRI. Methods: Deep learning-based detection of key brain landmarks on a whole-uterus EPI scan enables the subsequent fully automatic planning of the radiological single-shot Turbo Spin Echo acquisitions. The landmark detection pipeline was trained on over 120 datasets from varying field strength, echo times and resolutions and quantitatively evaluated. The entire automatic planning solution was tested prospectively in nine fetal subjects between 20 and 37 weeks. Comprehensive evaluation of all steps, the distance between manual and automatic landmarks, the planning quality and the resulting image quality was conducted. Results: Prospective automatic planning was performed in real-time without latency in all subjects. The landmark detection accuracy was 4.21+-2.56 mm for the fetal eyes and 6.47+-3.23 for the cerebellum, planning quality was 2.44/3 (compared to 2.56/3 for manual planning) and diagnostic image quality was 2.14 compared to 2.07 for manual planning. Conclusions: Real-time automatic planning of all three key fetal brain planes was successfully achieved and will pave the way towards simplifying the acquisition of fetal MRI thereby widening the availability of this modality in non-specialist centres.Comment: 17 pages, 8 figures, 1 table, MR

A genome-wide meta-analysis of palmoplantar pustulosis implicates TH2 responses and cigarette smoking in disease pathogenesis

\ua9 2024 The AuthorsBackground: Palmoplantar pustulosis (PPP) is an inflammatory skin disorder that mostly affects smokers and manifests with painful pustular eruptions on the palms and soles. Although the disease can present with concurrent plaque psoriasis, TNF and IL-17/IL-23 inhibitors show limited efficacy. There is therefore a pressing need to uncover PPP disease drivers and therapeutic targets. Objectives: We sought to identify genetic determinants of PPP and investigate whether cigarette smoking contributes to disease pathogenesis. Methods: We performed a genome-wide association meta-analysis of 3 North-European cohorts (n = 1,456 PPP cases and 402,050 controls). We then used the scGWAS program to investigate the cell-type specificity of the association signals. We also undertook genetic correlation analyses to examine the similarities between PPP and other immune-mediated diseases. Finally, we applied Mendelian randomization to analyze the causal relationship between cigarette smoking and PPP. Results: We found that PPP is not associated with the main genetic determinants of plaque psoriasis. Conversely, we identified genome-wide significant associations with the FCGR3A/FCGR3B and CCHCR1 loci. We also observed 13 suggestive (P < 5 7 10−6) susceptibility regions, including the IL4/IL13 interval. Accordingly, we demonstrated a significant genetic correlation between PPP and TH2-mediated diseases such as atopic dermatitis and ulcerative colitis. We also found that genes mapping to PPP-associated intervals were preferentially expressed in dendritic cells and often implicated in T-cell activation pathways. Finally, we undertook a Mendelian randomization analysis, which supported a causal role of cigarette smoking in PPP. Conclusions: The first genome-wide association study of PPP points to a pathogenic role for deregulated TH2 responses and cigarette smoking

Heterologous expression of cytotoxic sesquiterpenoids from the medicinal mushroom Lignosus rhinocerotis in yeast

Background: Genome mining facilitated by heterologous systems is an emerging approach to access the chemical diversity encoded in basidiomycete genomes. In this study, three sesquiterpene synthase genes, GME3634, GME3638, and GME9210, which were highly expressed in the sclerotium of the medicinal mushroom Lignosus rhinocerotis, were cloned and heterologously expressed in a yeast system. Results: Metabolite profile analysis of the yeast culture extracts by GC-MS showed the production of several sesquiterpene alcohols (C 15 H 26 O), including cadinols and germacrene D-4-ol as major products. Other detected sesquiterpenes include selina-6-en-4-ol, ß-elemene, ß-cubebene, and cedrene. Two purified major compounds namely (+)-torreyol and a-cadinol synthesised by GME3638 and GME3634 respectively, are stereoisomers and their chemical structures were confirmed by 1 H and 13 C NMR. Phylogenetic analysis revealed that GME3638 and GME3634 are a pair of orthologues, and are grouped together with terpene synthases that synthesise cadinenes and related sesquiterpenes. (+)-Torreyol and a-cadinol were tested against a panel of human cancer cell lines and the latter was found to exhibit selective potent cytotoxicity in breast adenocarcinoma cells (MCF7) with IC 50 value of 3.5 ± 0.58 µg/ml while a-cadinol is less active (IC 50 = 18.0 ± 3.27 µg/ml). Conclusions: This demonstrates that yeast-based genome mining, guided by transcriptomics, is a promising approach for uncovering bioactive compounds from medicinal mushrooms

Buckling analysis on the hull of the historic paddle steamer ‘Medway Queen’

This study presents modelling and finite element simulation and the subsequent buckling analysis on the the historic Medway Queen paddle steamer ship which is under reconstruction now. The objective of this study is to assess buckling strength of the hull plate due to the longitudinal stress in the hull plates of the Medway Queen under various sea and live load conditions. A beam finite element analysis with structural elements is utilised to assess shear stress and bending moments of the ship structure. The model predictions for longitudinal stresses in hull plates are combined with buckling assessments on the hull plates in different, judged to be the most critical, locations along the ship's length. The structural beam model is utilised to simulate the ship's stress behaviour under hogging and sagging conditions with three different wave heights and four sets of live loads. From the longitudinal bending moment and shear force of all 24 simulation cases, extreme locations are identified and critical buckling stress on the plates close to these locations is predicted and compared with actual axial and shear stresses on the hull plate to predict the condition at which the buckling structural failure occurs