Non‐coding RNAs in bone remodelling and bone metastasis : mechanisms of action and translational relevance

Bone metastases are frequent complications in patients with advanced cancer, which can be fatal or may rapidly impede the quality of life of patients. Current treatments for patients with bone metastases are palliative. Therefore, a better understanding of the molecular mechanisms that precede the overt development of skeletal lesions could lead to better therapeutic interventions. In this review, we present evidence that non‐coding RNAs (ncRNAs) such as long non‐coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs) are emerging as master regulators of bone metastasis formation. We highlight potential opportunities for the therapeutic targeting of ncRNAs. Furthermore, we discuss the possibility that ncRNAs may be used as biomarkers in the context of bone metastases, which might provide insight for improving the response to current bone‐targeting therapies

Practical quad mesh simplification

In this paper we present an innovative approach to incremental quad mesh simplification, i.e. the task of producing a low complexity quad mesh starting from a high complexity one. The process is based on a novel set of strictly local operations which preserve quad structure. We show how good tessellation quality (e.g. in terms of vertex valencies) can be achieved by pursuing uniform length and canonical proportions of edges and diagonals. The decimation process is interleaved with smoothing in tangent space. The latter strongly contributes to identify a suitable sequence of local modification operations. The method is naturally extended to manage preservation of feature lines (e.g. creases) and varying (e.g. adaptive) tessellation densities. We also present an original Triangle-to-Quad conversion algorithm that behaves well in terms of geometrical complexity and tessellation quality, which we use to obtain the initial quad mesh from a given triangle mesh

Practical quad mesh simplification

In this paper we present an innovative approach to incremental quad mesh simplification, i.e. the task of producing a low complexity quad mesh starting from a high complexity one. The process is based on a novel set of strictly local operations which preserve quad structure. We show how good tessellation quality (e.g. in terms of vertex valencies) can be achieved by pursuing uniform length and canonical proportions of edges and diagonals. The decimation process is interleaved with smoothing in tangent space. The latter strongly contributes to identify a suitable sequence of local modification operations. The method is naturally extended to manage preservation of feature lines (e.g. creases) and varying (e.g. adaptive) tessellation densities. We also present an original Triangle-to-Quad conversion algorithm that behaves well in terms of geometrical complexity and tessellation quality, which we use to obtain the initial quad mesh from a given triangle mesh

Loopy Cuts: Surface-Field Aware Block Decomposition for Hex-Meshing.

We present a new fully automatic block-decomposition hexahedral meshing algorithm capable of producing high quality meshes that strictly preserve feature curve networks on the input surface and align with an input surface cross-field. We produce all-hex meshes on the vast majority of inputs, and introduce localized non-hex elements only when the surface feature network necessitates those. The input to our framework is a closed surface with a collection of geometric or user-demarcated feature curves and a feature-aligned surface cross-field. Its output is a compact set of blocks whose edges interpolate these features and are loosely aligned with this cross-field. We obtain this block decomposition by cutting the input model using a collection of simple cutting surfaces bounded by closed surface loops. The set of cutting loops spans the input feature curves, ensuring feature preservation, and is obtained using a field-space sampling process. The computed loops are uniformly distributed across the surface, cross orthogonally, and are loosely aligned with the cross-field directions, inducing the desired block decomposition. We validate our method by applying it to a large range of complex inputs and comparing our results to those produced by state-of-the-art alternatives. Contrary to prior approaches, our framework consistently produces high-quality field aligned meshes while strictly preserving geometric or user-specified surface features

Transcranial Doppler Monitoring of Intracranial Pressure Plateau Waves

$\textbf{BACKGROUND}$: Transcranial Doppler (TCD) has been used to estimate ICP noninvasively (nICP); however, its accuracy varies depending on different types of intracranial hypertension. Given the high specificity of TCD to detect cerebrovascular events, this study aimed to compare four TCD-based nICP methods during plateau waves of ICP. $\textbf{METHODS}$: A total of 36 plateau waves were identified in 27 patients (traumatic brain injury) with TCD, ICP, and ABP simultaneous recordings. The nICP methods were based on: (1) interaction between flow velocity (FV) and ABP using a "black-box" mathematical model (\textit{nICP_BB}); (2) diastolic FV (\textit{nICP_FV}$_{d}$); (3) critical closing pressure (\textit{nICP_CrCP}), and (4) pulsatility index (\textit{nICP_PI}). Analyses focused on relative changes in time domain between ICP and noninvasive estimators during plateau waves and the magnitude of changes ($\textit{∆}$ between baseline and plateau) in real ICP and its estimators. A ROC analysis for an ICP threshold of 35 mmHg was performed. $\textbf{RESULTS}$: In time domain, \textit{nICP_PI, nICP_BB,} and \textit{nICP_CrCP} presented similar correlations: 0.80 ± 0.24, 0.78 ± 0.15, and 0.78 ± 0.30, respectively. \textit{nICP_FV}$_{d}$ presented a weaker correlation (R = 0.62 ± 0.46). Correlations between ∆ICP and ∆nICP were better represented by \textit{nICP_CrCP} and BB, R = 0.48, 0.44 (p < 0.05), respectively. \textit{nICP_FV}$_{d}$ and $\textit{PI}$ presented nonsignificant $\textit{∆}$ correlations. ROC analysis showed moderate to good areas under the curve for all methods: \textit{nICP_BB}, 0.82; \textit{nICP_FV}$_{d}$, 0.77; \textit{nICP_CrCP}, 0.79; and \textit{nICP_PI}, 0.81. $\textbf{CONCLUSIONS}$: Changes of ICP in time domain during plateau waves were replicated by nICP methods with strong correlations. In addition, the methods presented high performance for detection of intracranial hypertension. However, absolute accuracy for noninvasive ICP assessment using TCD is still low and requires further improvement

MicroRNAs and their roles in breast cancer bone metastasis

Bone metastasis occurs in advanced stages of breast cancer, worsening the quality of life and increasing the mortality of patients. Current treatments for bone metastasis are only palliative, and efficient therapeutic targets need to be still identified. MicroRNAs (miRNAs) are a large class of small non-coding RNAs that regulate gene expression within cells. Interestingly, the expression of certain miRNAs has been associated with several stages of bone metastasis progression, highlighting the importance of these small RNAs during the course of the metastatic disease. In this review, we aim to summarise the most recent findings on miRNAs and their mRNA targets in driving breast cancer bone metastasis. Furthermore, we discuss the possibility to use miRNAs as direct therapeutic targets or as advanced therapies for breast cancer bone metastasis, as well as their potential as predictive biomarkers of bone metastasis for an early diagnosis and a better tailoring of therapies for cancer patients

Magnetic coupling to the Advanced Virgo payloads and its impact on the low frequency sensitivity

We study the electromagnetic coupling of the Advanced Virgo (AdV) Input Mirror Payload (IMP) in response to a slowly time-varying magnetic field. As the problem is not amenable to analytical solution, we employ and validate a finite element (FE) analysis approach. The FE model is built to represent as faithfully as possible the real object and it has been validated by comparison with experimental measurements. The intent is to estimate the induced currents and the magnetic field in the neighbourhood of the payload. The procedure found 21 equivalent electrical configurations that are compatible with the measurements. These have been used to compute the magnetic noise contribution to the total AdV strain noise. At the current stage of development AdV seems to be unaffected by magnetic noise, but we foresee a non-negligible coupling once AdV reaches the design sensitivity.Comment: 8 pages, 8 figures, 2 table

H19 long noncoding RNA controls the mRNA decay promoting function of KSRP

Long noncoding RNAs (lncRNAs) interact with protein factors to regulate different layers of gene expression transcriptionally or posttranscriptionally. Here we report on the functional consequences of the unanticipated interaction of the RNA binding protein K homology-type splicing regulatory protein (KSRP) with the H19 lncRNA (H19). KSRP directly binds to H19 in the cytoplasm of undifferentiated multipotent mesenchymal C2C12 cells, and this interaction favors KSRP-mediated destabilization of labile transcripts such as myogenin. AKT activation induces KSRP dismissal from H19 and, as a consequence, myogenin mRNA is stabilized while KSRP is repurposed to promote maturation of myogenic microRNAs, thus favoring myogenic differentiation. Our data indicate that H19 operates as a molecular scaffold that facilitates effective association of KSRP with myogenin and other labile transcripts, and we propose that H19 works with KSRP to optimize an AKT-regulated posttranscriptional switch that controls myogenic differentiation