Temporal diffeomorphic Free Form Deformation to quantify changes induced by left and right bundle branch block and pacing

International audienceThis paper presents motion and deformation quantification results obtained from synthetic and in vitro phantom data provided by the second cardiac Motion Analysis Challenge at STACOM-MICCAI. We applied the Temporal Diffeomorphic Free Form Deformation (TDFFD) algorithm to the datasets. This algorithm builds upon a diffeomorphic version of the FFD, to provide a 3D + t continuous and differentiable transform. The similarity metric includes a comparison between consecutive images, and between a reference and each of the following images. Motion and strain accuracy were evaluated on synthetic 3D ultrasound sequences with known ground truth motion. Experiments were also conducted on in vitro acquisitions

Incompressible image registration using divergence-conforming B-splines

Anatomically plausible image registration often requires volumetric preservation. Previous approaches to incompressible image registration have exploited relaxed constraints, ad hoc optimisation methods or practically intractable computational schemes. Divergence-free velocity fields have been used to achieve incompressibility in the continuous domain, although, after discretisation, no guarantees have been provided. In this paper, we introduce stationary velocity fields (SVFs) parameterised by divergence-conforming B-splines in the context of image registration. We demonstrate that sparse linear constraints on the parameters of such divergence-conforming B-Splines SVFs lead to being exactly divergence-free at any point of the continuous spatial domain. In contrast to previous approaches, our framework can easily take advantage of modern solvers for constrained optimisation, symmetric registration approaches, arbitrary image similarity and additional regularisation terms. We study the numerical incompressibility error for the transformation in the case of an Euler integration, which gives theoretical insights on the improved accuracy error over previous methods. We evaluate the proposed framework using synthetically deformed multimodal brain images, and the STACOM11 myocardial tracking challenge. Accuracy measurements demonstrate that our method compares favourably with state-of-the-art methods whilst achieving volume preservation.Comment: Accepted at MICCAI 201

Fumarate drives EMT in renal cancer

Medical Research Counci

COVID-19 Roundtable

The past year was an unprecedentedly challenging period to humanity. The very concept of a pandemic indicates a profound impact across different regions and societal strata, rendering the idea of unscathed human lives almost unimaginable. Still, this image of COVID-19 as a global threat menacing us all must not be allowed to efface the specificity of individual or communal struggles. This caveat is particularly relevant in the context of gender and diversity studies – the pertinence of which has been underscored countlessly over the past months, especially in policy recommendations to the COVID-19 pandemic. From the disproportionately severe measures aggravating isolation and destitution among the elderly to the coalescence of sanitary regulations and the BLM protests or the fire in the Moria refugee camp and the resulting urgency to address the wellbeing of displaced people: issues that relate intimately to notions of marginalization continually surface adjacent to the health crisis proper. Whether explicitly or implicitly, these circumstances call for gender and diversity scholars to commit their expertise to the benefit of those inordinately affected by COVID-19 and the array of responses it has evoked worldwide. At the same time, the conditions affecting these groups and individuals also affect research activities and advocacy work on gender and diversity, inhibiting the active commitment and scholarly involvement the situation demands. In this Spring 2021 General Issue, the Journal of Diversity and Gender Studies (DiGeSt) sought to explore the paradoxes, contradictions and tensions scholars in our field have faced and continue to face during the current COVID-19 crisis. Transcending a formally academic register, the roundtable includes personal, situated accounts that engage tensions between the pandemic and scholarly work in diversity and gender studies

Pits and fissures: etch resistance in prismless enamel walls

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.Background: In a previous study to examine the nature of etching on the walls of fissures, there was a consistent result of resistance to deep etching on parts of the walls and a zone of lesser etching on part of the walls as evidenced by the uptake of stain. The staining had been used to examine the nature of the etch pattern. The aims of this study were to define the nature of this etch resistant area. Methods: A sample of 55 teeth, both molars and premolars, were divided into three groups. In the first group the wetting of fissures by the etchant was examined; the second group tested for the effects of pellicle-cuticle-debris or air entrapment on the etching process. The final group looked at alternative mechanical treatments of the fissure prior to etching. Results: The specimens split along the fissures showed clearly that the etch resistant zone was not due to lack of contact with the etchant or the presence of a pellicle-cuticle-debris covering, but to the presence of a prismless enamel structure. This study showed that this zone inhibited tag development on the fissure walls. Conclusions: The mechanical removal of this prismless layer of enamel within the fissure system should result in an improved bonding of a fissure sealant through better tag development, in turn leading to a reduction in the failure rate of a sealant used to prevent caries.MF Burrow, JF Burrow and OF Makinso

Fumarate is an epigenetic modifier that elicits epithelial-to-mesenchymal transition.

Mutations of the tricarboxylic acid cycle enzyme fumarate hydratase cause hereditary leiomyomatosis and renal cell cancer. Fumarate hydratase-deficient renal cancers are highly aggressive and metastasize even when small, leading to a very poor clinical outcome. Fumarate, a small molecule metabolite that accumulates in fumarate hydratase-deficient cells, plays a key role in cell transformation, making it a bona fide oncometabolite. Fumarate has been shown to inhibit α-ketoglutarate-dependent dioxygenases that are involved in DNA and histone demethylation. However, the link between fumarate accumulation, epigenetic changes, and tumorigenesis is unclear. Here we show that loss of fumarate hydratase and the subsequent accumulation of fumarate in mouse and human cells elicits an epithelial-to-mesenchymal-transition (EMT), a phenotypic switch associated with cancer initiation, invasion, and metastasis. We demonstrate that fumarate inhibits Tet-mediated demethylation of a regulatory region of the antimetastatic miRNA cluster mir-200ba429, leading to the expression of EMT-related transcription factors and enhanced migratory properties. These epigenetic and phenotypic changes are recapitulated by the incubation of fumarate hydratase-proficient cells with cell-permeable fumarate. Loss of fumarate hydratase is associated with suppression of miR-200 and the EMT signature in renal cancer and is associated with poor clinical outcome. These results imply that loss of fumarate hydratase and fumarate accumulation contribute to the aggressive features of fumarate hydratase-deficient tumours.This work was supported by the Medical Research Council (UK). S.F. was supported by a Herchel Smith Research Studentship and K.F. by an MRC Career Development Award. E.R.M is supported by the ERC Advanced Researcher award 323004–ONCOTREAT. P.H.M. is supported by Senior Investigator Awards from the Wellcome Trust and NIHR. The Cambridge Human Research Tissue Bank and A.W. are supported by the NIHR Cambridge Biomedical Research Centre.This is the author accepted manuscript. The final version is available from Nature Publishing at http://dx.doi.org/10.1038/nature19353

SNAI1 expression and the mesenchymal phenotype: an immunohistochemical study performed on 46 cases of oral squamous cell carcinoma

Abstract Background SNAI1 can initiate epithelial-mesenchymal transition (EMT), leading to loss of epithelial characteristics and, in cancer, to invasion and metastasis. We hypothesized that SNAI1 reactivation occurs in oral squamous cell carcinoma (OSCC) where it might also be associated with focal adhesion kinase (FAK) expression and p63 loss. Methods Immunohistochemistry was performed on 46 tumors and 26 corresponding lymph node metastases. Full tissue sections were examined to account for rare and focal expression. Clinical outcome data were collected and analyzed. Results SNAI1-positivity (nuclear, ≥ 5% tumor cells) was observed in 10 tumors and 5 metastases (n = 12 patients). Individual SNAI1(+) tumor cells were seen in primary tumors of 30 patients. High level SNAI1 expression (>10% tumor cells) was rare, but significantly associated with poor outcome. Two cases displayed a sarcomatoid component as part of the primary tumor with SNAI1(+)/FAK(+)/E-cadherin(-)/p63(-) phenotype, but disparate phenotypes in corresponding metastases. All cases had variable SNAI1(+) stroma. A mesenchymal-like immunoprofile in primary tumors characterized by E-cadherin loss (n = 29, 63%) or high cytoplasmic FAK expression (n = 10, 22%) was associated with N(+) status and tumor recurrence/new primary, respectively. Conclusions SNAI1 is expressed, although at low levels, in a substantial proportion of OSCC. High levels of SNAI1 may herald a poor prognosis and circumscribed SNAI1 expression can indicate the presence of a sarcomatoid component. Absence of p63 in this context does not exclude squamous tumor origin. Additional EMT inducers may contribute to a mesenchymal-like phenotype and OSCC progression

Key signalling nodes in mammary gland development and cancer. The Snail1-Twist1 conspiracy in malignant breast cancer progression

Breast cancer is the most common cancer among women, and despite significant advances in diagnosing and treating it, metastatic spread of cancer cells results in a high mortality rate. Epithelial-to-mesenchymal transition (EMT) is an embryonic program in which epithelial cells lose their characteristics and gain mesenchymal features. Therefore, EMT might play a very important role during malignant tumour progression. In this review we summarise recent advances in breast cancer research with a particular focus on the transcription factors Snail1 and Twist1. Besides discussing the role of EMT in normal mammary gland development, we describe regulatory mechanisms involving newly discovered upstream regulators and microRNAs, the association of EMT with breast cancer stem cells, and the involvement of the tumour microenvironment in breast cancer progression

Atlas construction and image analysis using statistical cardiac models

International audienceThis paper presents a brief overview of current trends in the construction of population and multi-modal heart atlases in our group and their application to atlas-based cardiac image analysis. The technical challenges around the construction of these atlases are organized around two main axes: groupwise image registration of anatomical, motion and fiber images and construction of statistical shape models. Application-wise, this paper focuses on the extraction of atlas-based biomarkers for the detection of local shape or motion abnormalities, addressing several cardiac applications where the extracted information is used to study and grade different pathologies. The paper is concluded with a discussion about the role of statistical atlases in the integration of multiple information sources and the potential this can bring to in-silico simulations