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

Neural bases of reward anticipation in healthy individuals with low, mid, and high levels of schizotypy

A growing body of research has placed the ventral striatum at the center of a network of cerebral regions involved in anticipating rewards in healthy controls. However, little is known about the functional connectivity of the ventral striatum associated with reward anticipation in healthy controls. In addition, few studies have investigated reward anticipation in healthy humans with different levels of schizotypy. Here, we investigated reward anticipation in eighty-four healthy individuals (44 females) recruited based on their schizotypy scores. Participants performed a variant of the Monetary Incentive Delay Task while undergoing event-related fMRI.Participants showed the expected decrease in response times for highly rewarded trials compared to non-rewarded trials. Whole-brain activation analyses replicated previous results, including activity in the ventral and dorsal striatum. Whole-brain psycho-physiological interaction analyses of the left and right ventral striatum revealed increased connectivity during reward anticipation with widespread regions in frontal, parietal and occipital cortex as well as the cerebellum and midbrain. Finally, we found no association between schizotypal personality severity and neural activity and cortico-striatal functional connectivity. In line with the motivational, attentional, and motor functions of rewards, our data reveal multifaceted cortico-striatal networks taking part in reward anticipation in healthy individuals. The ventral striatum is connected to regions of the salience, attentional, motor and visual networks during reward anticipation and thereby in a position to orchestrate optimal goal-directed behavior

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