A coordinate deregulation of microRNAs expressed in mucosa adjacent to tumor predicts relapse after resection in localized colon cancer

Up to 20% of colorectal cancer (CRC) node-negative patients develop loco-regional or distant recurrences within 5 years from surgery. No predictive biomarker able to identify the node-negative subjects at high risk of relapse after curative treatment is presently available.Forty-eight localized (i.e. stage I-II) colon cancer patients who underwent radical tumor resection were considered. The expression of five miRNAs, involved in CRC progression, was investigated by qRT-PCR in both tumor tissue and matched normal colon mucosa.Interestingly, we found that the coordinate deregulation of four miRNAs (i.e. miR-18a, miR-21, miR-182 and miR-183), evaluated in the normal mucosa adjacent to tumor, is predictive of relapse within 55 months from curative surgery.Our results, if confirmed in independent studies, may help to identify high-risk patients who could benefit most from adjuvant therapy. Moreover, this work highlights the importance of extending the search for tissue biomarkers also to the tumor-adjacent mucosa

Nonparametric Sparsity and Regularization

In this work we are interested in the problems of supervised learning and variable selection when the input-output dependence is described by a nonlinear function depending on a few variables. Our goal is to consider a sparse nonparametric model, hence avoiding linear or additive models. The key idea is to measure the importance of each variable in the model by making use of partial derivatives. Based on this intuition we propose and study a new regularizer and a corresponding least squares regularization scheme. Using concepts and results from the theory of reproducing kernel Hilbert spaces and proximal methods, we show that the proposed learning algorithm corresponds to a minimization problem which can be provably solved by an iterative procedure. The consistency properties of the obtained estimator are studied both in terms of prediction and selection performance. An extensive empirical analysis shows that the proposed method performs favorably with respect to the state-of-the-art

Iterative Projection Methods for Structured Sparsity Regularization

In this paper we propose a general framework to characterize and solve the optimization problems underlying a large class of sparsity based regularization algorithms. More precisely, we study the minimization of learning functionals that are sums of a differentiable data term and a convex non differentiable penalty. These latter penalties have recently become popular in machine learning since they allow to enforce various kinds of sparsity properties in the solution. Leveraging on the theory of Fenchel duality and subdifferential calculus, we derive explicit optimality conditions for the regularized solution and propose a general iterative projection algorithm whose convergence to the optimal solution can be proved. The generality of the framework is illustrated, considering several examples of regularization schemes, including l1 regularization (and several variants), multiple kernel learning and multi-task learning. Finally, some features of the proposed framework are empirically studied

Rapid, comprehensive analysis of the dystrophin transcript by a custom micro-fluidic exome array

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Neuropsychiatric performance and treatment of hepatitis C with direct-acting antivirals: a prospective study

Background: Since direct-acting antivirals (DAAs) have been approved for the treatment of hepatitis C virus (HCV) infection, a small series of patients with new-onset neuropsychiatric alterations have been referred to us. We therefore set out to study neuropsychiatric function in relation to DAAs prospectively. Methods: Ten patients with cirrhosis and 12 post-liver transplant (post-LT) patients were enrolled. All underwent wake electroencephalography (EEG) and a neuropsychological evaluation (paper and pencil battery, simple/choice reaction times, working memory task) at baseline, at the end of treatment with DAAs and after 6 months. At the same time points, full blood count, liver/kidney function tests, quantitative HCV RNA, ammonia and immunosuppressant drug levels were obtained, as appropriate. Results: Patients with cirrhosis were significantly older than post-LT patients (65\ub112 vs 55\ub17 years; P<0.05). Neuropsychological performance and wake EEG were comparable in the two groups at baseline. At the end of a course of treatment with DAAs, a significant slowing in choice reaction times and in the EEG (increased relative delta power) was observed in patients with cirrhosis, which resolved after 6 months. In contrast, no significant changes over time were observed in the neuropsychiatric performance of post-LT patients. No significant associations were observed between neuropsychiatric performance and stand-alone/combined laboratory variables. Conclusion: Some degree of neuropsychiatric impairment was observed in relation to treatment with DAAs in patients with cirrhosis, but not in post-LT patients, suggesting that the former may be sensitive to mild DAA neurotoxicity

UWB Path Loss Models for Ingestible Devices

[EN] Currently, some medical devices such as the Wireless Capsule Endoscopy (WCE) are used for data transmission from inside to outside the body. Nevertheless, for certain applications such as WCE, the data rates offered by current medical frequency bands can result insufficient. Ultra Wideband (UWB) frequency band has become an interesting solution for this. However, to date, there is not a formal channel path loss model for the UWB frequency band in the gastrointestinal (GI) scenario due to the huge differences between the proposed studies. There are three main methodologies to characterize the propagation channel, software simulations and experimental measurements either in phantom or in in vivo animals. Previous works do not compare all the methodologies or present some disagreements with the literature. In this paper, a dedicated study of the path loss using the three methodologies aforementioned (simulations, phantoms and in vivo measurements) and a comparison with previous researches in the literature is performed. Moreover, numerical values for a path loss model which agrees with the three methodologies and the literature are proposed. This paper aims at being the starting point for a formal path loss model in the UWB frequency band for WBANs in the GI scenarioThis work was supported in part by the European Union's H2020-MSCA-ITN Program for the "Wireless In-body Environment Communication" Project under Grant 675353, in part by the Programa de Ayudas de Investigacion y Desarrollo (PAID-01-16) from Universitat Politecnica de Valencia, and in part by the Ministerio de Economia y Competitividad, Spain under Grant TEC2014-60258-C2-1-R through the European FEDER Funds.Pérez-Simbor, S.; Andreu-Estellés, C.; Garcia-Pardo, C.; Frasson, M.; Cardona Marcet, N. (2019). UWB Path Loss Models for Ingestible Devices. IEEE Transactions on Antennas and Propagation. 67(8):5025-5034. https://doi.org/10.1109/TAP.2019.2891717S5025503467

Polymorphism rs7214723 in CAMKK1: a new genetic variant associated with cardiovascular diseases

Cardiovascular diseases (CVDs) are the leading cause of deaths worldwide. CVDs have a complex etiology due to the several factors underlying its development including environment, lifestyle, and genetics. Given the role of calcium signal transduction in several CVDs, we investigated via PCR-restriction fragment length polymorphism (RFLP) the single nucleotide polymorphism (SNP) rs7214723 within the calcium/calmodulin-dependent kinase kinase 1 (CAMKK1) gene coding for the Ca2+/calmodulin-dependent protein kinase kinase I. The variant rs7214723 causes E375G substitution within the kinase domain of CAMKK1. A cross-sectional study was conducted on 300 cardiac patients. RFLP-PCR technique was applied, and statistical analysis was performed to evaluate genotypic and allelic frequencies and to identify an association between SNP and risk of developing specific CVD. Genotype and allele frequencies for rs7214723 were statistically different between cardiopathic and several European reference populations. A logistic regression analysis adjusted for gender, age, diabetes, hypertension, BMI and previous history of malignancy was applied on cardiopathic genotypic data and no association was found between rs7214723 polymorphism and risk of developing specific coronary artery disease (CAD) and aortic stenosis (AS). These results suggest the potential role of rs7214723 in CVD susceptibility as a possible genetic biomarker

Amorphous solid dispersions of curcumin in a poly(ester amide): antiplasticizing effect on the glass transition and macromolecular relaxation dynamics, and controlled release

In order to exploit the pharmacological potential of natural bioactive molecules with low water solubility, such as curcumin, it is necessary to develop formulations, such as amorphous polymer dispersions, which allow a constant release rate and at the same time avoid possible toxicity effects of the crystalline form of the molecule under scrutiny. In this study, polymer dispersions of curcumin were obtained in PADAS, a biodegradable semicrystalline copolymer based on 1,12-dodecanediol, sebacic acid and alanine. The dispersions were fully characterized by means of differential scanning calorimetry and broadband dielectric spectroscopy, and the drug release profile was measured in a simulated body fluid. Amorphous homogeneous binary dispersions were obtained for curcumin mass fraction between 30 and 50%. Curcumin has significantly higher glass transition temperature Tg (˜ 347 K) than the polymer matrix (˜274-277 K depending on the molecular weight), and dispersions displayed Tg’s intermediate between those of the pure amorphous components, implying that curcumin acts as an effective antiplasticizer for PADAS. Dielectric spectroscopy was employed to assess the relaxation dynamics of the binary dispersion with 30 wt% curcumin, as well as that of each (amorphous) component separately. The binary dispersion was characterized by a single structural relaxation, a single Johari-Goldstein process, and two local intramolecular processes, one for each component. Interestingly, the latter processes scaled with the Tg of the sample, indicating that they are viscosity-sensitive. In addition, both the pristine polymer and the dispersion exhibited an interfacial Maxwell-Wagner relaxation, likely due to spatial heterogeneities associated with phase disproportionation in this polymer. The release of curcumin from the dispersion in a simulated body fluid followed a Fickian diffusion profile, and 51% of the initial curcumin content was released in 48 h.Peer ReviewedPostprint (published version

Estimating moisture content and hydraulic properties of unsaturated sandy soils of Tiber River (Central Italy): integrating data from calibrated PR2/6 probe and hydraulic property estimator

The correct estimation of soil moisture data is essential in soil-water management and estimating the hydraulic properties of unsaturated soils. The increased use of Multi-Sensor Capacitance Probes (MCAPs) requires careful calibration. Without accurate calibration, the use of MCAPs leads to incorrect water content estimation, making them of no practical use. This work presents the specific calibration equations for the correct use of the PR2/6 profile probe on sands of different nature. As the iron oxides content of the Tiber River basin sands increases, the calibration lines slope increases, allowing the understanding of the different electromagnetic responses. As for other sands worldwide, sands with high iron oxides content show a relative high specific surface than quartz or calcareous sands, responsible for more adhesive water (e.g., high permittivity values). The water content data are integrated with a hydraulic property estimator allowing the estimation of the hydraulic conductivity of soils. Applying the manufacturer equation of the PR2/6 profile probe instead of the specific equation leads to an overestimation of the hydraulic conductivity values up to two orders of magnitude, making therefore rather incorrect the understanding of the phenomena occurring in the unsaturated zone