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Can Diffusion Models Bridge the Domain Gap in Cardiac MR Imaging?
No full textMagnetic resonance (MR) imaging, including cardiac MR, is prone to domain shift due to variations in imaging devices and acquisition protocols. This challenge limits the deployment of trained AI models in real-world scenarios, where performance degrades on unseen domains. Traditional solutions involve increasing the size of the dataset through ad-hoc image augmentation or additional online training/transfer learning, which have several limitations. Synthetic data offers a promising alternative, but anatomical/structural consistency constraints limit the effectiveness of generative models in creating image-label pairs. To address this, we propose a diffusion model (DM) trained on a source domain that generates synthetic cardiac MR images that resemble a given reference. The synthetic data maintains spatial and structural fidelity, ensuring similarity to the source domain and compatibility with the segmentation masks. We assess the utility of our generative approach in multi-centre cardiac MR segmentation, using the 2D nnU-Net, 3D nnU-Net and vanilla U-Net segmentation networks. We explore domain generalisation, where, domain-invariant segmentation models are trained on synthetic source domain data, and domain adaptation, where, we shift target domain data towards the source domain using the DM. Both strategies significantly improved segmentation performance on data from an unseen target domain, in terms of surface-based metrics (Welch’s t-test, p < 0.01), compared to training segmentation models on real data alone. The proposed method ameliorates the need for transfer learning or online training to address domain shift challenges in cardiac MR image analysis, especially useful in data-scarce settings
A randomised, placebo-controlled trial in healthy humans of modified cellulose or psyllium evaluating the role of gelation in altering colonic gas production during inulin co-administration
Get PDFDietary fibre is vital for a healthy diet, yet many people avoid it because of symptoms induced by colonic gas. Slowing rapid fermentation decreases colonic distention and reduces symptoms, allowing for better tolerance of prebiotics. Co-administration of inulin, a fermentable fibre, with psyllium, a gel-forming fibre, reduces gas production in irritable bowel syndrome patients compared to administering inulin alone, but the underlying mechanism is unclear. We hypothesise that psyllium polysaccharides’ physically cross-linked gel resists gastrointestinal shear forces and impairs microbial access to inulin, thereby delaying fermentation. Methylcellulose is another physically cross-linked fibre ingredient, widely used in food production for its tunability and affordability. Our aim was to develop a preparation of methylcellulose of comparable functionality to psyllium. A formulation of methylcellulose with comparable rheological and inulin release behaviour was developed in vitro. We subsequently performed a randomised, three-way, placebo-controlled non-inferiority study with healthy volunteers (n = 30), comparing the slowing of fermentation of inulin by co-administering with psyllium, methylcellulose or a control maltodextrin. Fermentation in vivo was assessed by breath hydrogen measurements for 24 hours after ingestion. While psyllium significantly reduced initial breath hydrogen production compared to the placebo, a non-inferior effect on reduction in initial breath hydrogen with methylcellulose was not demonstrated. Despite similar physicochemical properties, psyllium and methylcellulose hydrogels exhibited different transit behaviour based on the breath hydrogen time to rise >10 ppm and time to peak. We hypothesise that the fast reformation of psyllium's polysaccharide network or “self-healing” properties after deformation by intestinal pressure waves may underpin its effectiveness in slowing fermentation. The clinical trial registry number is NCT05911347 (https://clinicaltrials.gov)
Detecting social differences in diet in medieval towns:isotopic evidence from Cambridge, England, c. AD 940–1538
Get PDFThe analysis of stable carbon and nitrogen isotopes in bone collagen can reveal aspects of diet and how this may change between periods and places. Here, the authors apply a ‘whole-town’ approach to isotopic analysis, to characterise and explore variation in diet within medieval Cambridge and its hinterland. By adopting this approach, and a robust isotopic baseline, the authors argue that the number of confounding variables that typically plague archaeometric research are reduced, allowing for more nuanced interpretation of data. For medieval Cambridge, this nuance comes in the form of inter-site comparisons in the lived experience of social differentiation
Single versus repeated intravenous oncolytic reovirus infusions: Implications for immune modulation and rationalised scheduling of therapy in hepatocellular carcinoma
Get PDFScheduling of oncolytic virus (OV) therapy has never been correlated with immunological/clinical response. In hepatocellular carcinoma (HCC) patients, where background liver is frequently chronically injured, repeated dosing may have deleterious implications, resulting in off-target immune-mediated damage, thereby tipping the balance between favourable clinical response and hepatotoxicity. Elucidation of the optimum dosing regime is paramount to ensure therapy, whilst limiting damage to background liver. We expand upon our experience in neoadjuvant OV therapy to compare immunological responses from single versus repeated doses of reovirus in cancer patients. The impact of OV on HCC outcomes was examined in vivo following a high-fat diet or induced liver fibrosis in the context of abnormal background liver. Furthermore, we assess the potential immune-mediated toxicity of single versus multiple virus infusions in combination with PD-1/PD-L1 blockade. Data indicate that a single dose of reovirus is equivalent or superior to repeated doses in achieving: (a) induction of an inflammatory cytokine/chemokine response; (b) peripheral blood immune cell activation; (c) migration of activated CD8+ CTLs. Repeated doses on consecutive days do not improve the amplitude of the immune response following virus infusion. Furthermore, without improving therapeutic efficacy, repeated viral dosing leads to an unwanted influx of activated T-cells into background liver, alongside elevated liver enzymes associated with aberrant liver function. A single dose of reovirus is as effective as multiple doses when combined with anti-PD-L1 therapy in limiting tumour growth and extending survival in vivo, whilst simultaneously avoiding undesirable toxicities in background liver, in the context of HCC
Characterising the shear, stretch and in-plane bending response of a pure-unidirectional non-crimp fabric
No full textThe in-plane deformation kinematics of a pure-Unidirectional Non-Crimp Fabric (pure-UDNCF) is investigated using novel and existing experimental methods to characterise its shear, tensile, and in-plane bending responses under controlled loading. A pure-UDNCF is defined as a fabric in which stabilising tows are absent in the transverse direction relative to the primary tow orientation. The stitching threads in this fabric are made of polyamide, a highly compliant material that allows significant stretch, introducing a low-energy deformation mode that is relatively absent in biaxial engineering fabrics and quasi-UDNCFs (UDNCFs with inextensible stitching and transverse stabilising fibres). To fully characterise its forming behaviour, several novel testing methods are introduced that generate well-defined combinations of fabric shear, in-plane bending and stitch tensile strain. The total normalised axial force measured in the tests is subsequently decoupled into three contributions from shear, tensile strain in the stitch direction, and in-plane bending of the tows. An important finding is that when tested in the picture frame test, in-plane bending generates more resistance to specimen deformation than shearing of the fabric. The testing protocol and resulting data can be used to create appropriate constitutive models for pure-UDNCFs
Tuning surface microtopography for optimum thermocompression bonding performance: structure, process parameters, and mechanisms on microfluidic chips
Get PDFThe widespread application of microfluidic chips in biomedicine, life sciences, and food safety has generated industrialization demands, making it necessary to address key challenges in production costs and scalability. This work proposes the fabrication of an innovative microstructure in microfluidic chips to enhance thermocompression bonding performance. Through simulation, the stress mitigation effect of the energy-gathering rib (ER) and the resulting microchannel deformation are analyzed. This analysis subsequently feeds a redesign of the initial reference microchannel structure, acting as a guide. Experimental validation follows to confirm the enhancement of bonding performance by the ER. Results demonstrate that compared to the initial microchannel, the new design increases bonding strength by 123 % and reduces microchannel deformation by 6–8.46 %. Further analysis reveals that bonding strength increases by 160 % in the pressure range of 0.6–1.56 MPa. Additionally, this work advances the general understanding of the bonding strength formation mechanism by clearly elucidating the evolutionary behavior of interfacial morphology at the bonded interface. The generated knowledge accelerates the commercialization of microfluidic chips by directly improving the economic efficiency and sustainability of the fabrication process
Commentary: Autoimmune/Autoinflammatory Syndrome Induced by Adjuvants (ASIA Syndrome) After Polypropylene Mesh Implantation – Protocol of a Pilot Study for Diagnostics and Treatment
Get PDFParallel evolution of plant alkaloid biosynthesis from bacterial-like decarboxylases
Get PDFAlkaloids are nitrogen-containing natural products derived from amino acids. The basic amino acids lysine and ornithine are precursors to a wide range of alkaloids including the bioactive compounds nicotine, hyoscyamine and securinine. Isotope feeding experiments have shown that the amino acids can be incorporated into alkaloids in a symmetric or nonsymmetric manner. The symmetric pathway is catalysed by two enzymes, a decarboxylase and oxidase, forming a cyclic iminium which acts as the electrophile in the scaffold forming step. Here, we describe the ornithine/lysine/arginine decarboxylase-oxidases (OLADOs), PLP-dependent enzymes responsible for the nonsymmetric pathway, catalysing the single step decarboxylative oxidative deamination of lysine, ornithine or arginine. These enzymes are part of the group III ornithine/lysine/arginine decarboxylase-like family (OLADLs), previously exclusively associated with prokaryotes. We reveal OLADLs to be widespread in plants and show that OLADOs have repeatedly emerged through parallel evolution from OLADLs, via similar active site substitutions. This investigation introduces a new class of eukaryotic decarboxylases, and describes enzymes involved in multiple alkaloid biosynthesis pathways. It furthermore demonstrates how the principle of parallel evolution at a genomic and enzymatic level can be leveraged for gene discovery across multiple lineages
Deep-ultraviolet ptychographic pocket-scope (DART): mesoscale lensless molecular imaging with label-free spectroscopic contrast
Get PDFThe mesoscale characterization of biological specimens has traditionally required compromises between resolution, field-of-view, depth-of-field, and molecular specificity, with most approaches relying on external labels. Here we present the Deep-ultrAviolet ptychogRaphic pockeT-scope (DART), a handheld platform that transforms label-free molecular imaging through intrinsic deep-ultraviolet spectroscopic contrast. By leveraging biomolecules’ natural absorption fingerprints and combining them with lensless ptychographic microscopy, DART resolves down to 308-nm linewidths across centimeter-scale areas while maintaining millimeter-scale depth-of-field. The system’s virtual error-bin methodology effectively eliminates artifacts from limited temporal coherence and other optical imperfections, enabling high-fidelity molecular imaging without lenses. Through differential spectroscopic imaging at deep-ultraviolet wavelengths, DART quantitatively maps nucleic acid and protein distributions with femtogram sensitivity, providing an intrinsic basis for explainable virtual staining. We demonstrate DART’s capabilities through imaging of tissue sections, cytopathology specimens, blood cells, and neural populations, revealing detailed molecular contrast without external labels. The combination of high-resolution molecular mapping and broad mesoscale imaging in a portable platform opens new possibilities from rapid clinical diagnostics, tissue analysis, to biological characterization in space exploration
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