Learning Non-linear Structures with Gaussian Markov Random Fields

AbstractNowadays, one of the most changeling points in statistics is the analysis of high dimensional data. In such cases, it is commonly assumed that the dimensionality of the data is only artificially high: although each data point is described by thousands of features, it is assumed that it can be modeled as a function of only a few underlying parameters. Formally, it is assumed that the data points are samples from a low-dimensional manifold embedded in a high-dimensional space.In this paper, we discuss a recently proposed method, known as Maximum Entropy Unfolding (MEU), for learning non-linear structures that characterize high dimensional data.This method represents a new perspective on spectral dimensionality reduction and, joined with the theory of Gaussian Markov random fields, provides a unifying probabilistic approach to spectral dimensionality reduction techniques. Parameter estimation as well as approaches to learning the structure of the GMRF are discusse

Simple Structure Detection Through Bayesian Exploratory Multidimensional IRT Models

In modern validity theory, a major concern is the construct validity of a test, which is commonly assessed through confirmatory or exploratory factor analysis. In the framework of Bayesian exploratory Multidimensional Item Response Theory (MIRT) models, we discuss two methods aimed at investigating the underlying structure of a test, in order to verify if the latent model adheres to a chosen simple factorial structure. This purpose is achieved without imposing hard constraints on the discrimination parameter matrix to address the rotational indeterminacy. The first approach prescribes a 2-step procedure. The parameter estimates are obtained through an unconstrained MCMC sampler. The simple structure is, then, inspected with a post-processing step based on the Consensus Simple Target Rotation technique. In the second approach, both rotational invariance and simple structure retrieval are addressed within the MCMC sampling scheme, by introducing a sparsity-inducing prior on the discrimination parameters. Through simulation as well as real-world studies, we demonstrate that the proposed methods are able to correctly infer the underlying sparse structure and to retrieve interpretable solutions

MiRNAs as Potential Prognostic Biomarkers for Metastasis in Thin and Thick Primary Cutaneous Melanomas.

Background/Aim: The identification of novel prognostic biomarkers for melanoma metastasis is essential to improve patient outcomes. To this aim, we characterized miRNA expression profiles in relation to metastasis in melanoma and correlated miRNAs expression with clinicalpathological factors. Materials and Methods: MiR-145-5p, miR-150-5p, miR-182-5p, miR-203-3p, miR-205-5p and miR211-5p expression levels were analyzed in primary cutaneous melanomas, including thin and thick melanomas, and in melanoma metastases by quantitative Real-Time PCR. Results: A significantly lower miR-205-5p expression was found in metastases compared to primary melanomas. Furthermore, a progressive down-regulation of miR-205-5p expression was observed from loco-regional to distant metastasis. Significantly lower miR-145-5p and miR-203-3p expression levels were found in cases with Breslow thickness >1 mm, high Clark level, ulceration and mitotic rate ≥1/mm2. Conclusion: Our findings point to miR-205-5p as potential biomarker of distant metastases and to miR-145-5p and miR-203-3p as markers of aggressiveness in melanoma

Metastases risk in thin cutaneous melanoma: Prognostic value of clinical-pathologic characteristics and mutation profile

Background: A high percentage of patients with thin melanoma (TM), defined as lesions with Breslow thickness ≤1 mm, presents excellent long-term survival, however, some patients develop metastases. Existing prognostic factors cannot reliably differentiate TM patients at risk for metastases. Objective: We aimed at characterizing the clinical-pathologic and mutation profile of metastatic and not-metastatic TM in order to distinguish lesions at risk of metastases. Methods: Clinical-pathologic characteristics were recorded for the TM cases analyzed. We used a Next Generation Sequencing (NGS) multi-gene panel to characterize TM for multiple somatic mutations. Results: A statistically significant association emerged between the presence of metastases and Breslow thickness ≥0.6 mm (p=0.003). None of TM with lymph-node involvement had Breslow thickness < 0.6 mm. Somatic mutations were identified in 19 of 21 TM analyzed (90.5%). No mutations were observed in two not-metastatic cases with the lowest Breslow thickness (≤0.4 mm), whereas mutations in more than one gene were detected in one metastatic case with the highest Breslow thickness (1.00 mm). Conclusion: Our study indicates Breslow thickness ≥0.6 mm as a valid prognostic factor to distinguish TM at risk for metastases

Effects of probiotic bacteria (VSL#3) on the polyamine biosynthesis and cell proliferation of normal colonic mucosa of rats

Abstract. Background: Probiotics seem to possess tumour inhibitory properties, but few studies have investigated their actions on the cell proliferation of normal colonic mucosa. The effects of a probiotic mixture (VSL#3) on polyamine biosynthesis, Ki-67 levels and apoptosis in the normal colon of rats were studied. Materials and Methods: For a 4-week period, 20 rats were fed a VSL#3 solution and 20 rats a saline solution. Samples from the colonic mucosa were collected at the end of treatment. Polyamines were detected by HPLC, ornithine decarboxylase activity by a radiometric technique, and apoptosis and Ki-67 by histochemical and immunohistochemical methods. Results: VSL#3 caused a significant decrease in colonic polyamine levels, ornithine decarboxylase activity and Ki-67 compared to controls. A significant increase in the apoptotic index was also observed. Conclusion: Probiotics could also reduce proliferation rates in a condition not affected by hyperproliferative or neoplastic growth, when the normal control mechanisms are still completely effective

Influence of ursodeoxycholate-enriched diet on liver tumor growth in HBV transgenic mice.

Hepatitis B virus (HBV) transgenic mice (official designation, Tg [Alb-1 HBV] Bri 44) invariably develop macroscopically evident tumors within the 20th month of life. Sustained proliferative activity seems to play an important role in the development of these lesions. We previously showed that ursodeoxycholate (UDC) stimulates hepatocyte proliferation in various experimental settings. Herein, we tested the assumption that biological factors able to further increase liver cell proliferation, such as UDC, could accelerate tumor development in this animal model. For this study, 22 eight-week-old male transgenic mice were divided into 2 groups; 11 animals received a standard diet, and 11 received a UDC-enriched diet. The 2 groups were further divided into 2 subgroups of 5 and 6 animals each and were sacrificed at 3 and 15 months of age, respectively. These different times were chosen to exclude diet-related toxicity (in 3-month-old mice) and evaluate tumor growth (in 15-month-old mice). In addition, hepatocyte proliferation was assessed in all animals. In 3-month-old mice receiving UDC, cholestatic and cytolytic indices as well as liver histology were comparable to those in controls. At 15 months, all UDC-treated mice showed large multinodular tumors whereas only 33% of controls developed smaller uninodular neoplasms. Hepatocyte proliferation was increased in all animals receiving UDC compared with controls. In conclusion, the increase in serum UDC (undetectable in mice fed a standard diet), in the absence of any toxic effect on the liver, suggests the involvement of this bile salt in the stimulation of hepatocyte proliferation and tumor growth

A simplified genomic profiling approach predicts outcome in metastatic colorectal cancer

The response of metastatic colorectal cancer (mCRC) to the first-line conventional combination therapy is highly variable, reflecting the elevated heterogeneity of the disease. The genetic alterations underlying this heterogeneity have been thoroughly characterized through omic approaches requiring elevated efforts and costs. In order to translate the knowledge of CRC molecular heterogeneity into a practical clinical approach, we utilized a simplified Next Generation Sequencing (NGS) based platform to screen a cohort of 77 patients treated with first-line conventional therapy. Samples were sequenced using a panel of hotspots and targeted regions of 22 genes commonly involved in CRC. This revealed 51 patients carrying actionable gene mutations, 22 of which carried druggable alterations. These mutations were frequently associated with additional genetic alterations. To take into account this molecular complexity and assisted by an unbiased bioinformatic analysis, we defined three subgroups of patients carrying distinct molecular patterns. We demonstrated these three molecular subgroups are associated with a different response to first-line conventional combination therapies. The best outcome was achieved in patients exclusively carrying mutations on TP53 and/or RAS genes. By contrast, in patients carrying mutations in any of the other genes, alone or associated with mutations of TP53/RAS, the expected response is much worse compared to patients with exclusive TP53/RAS mutations. Additionally, our data indicate that the standard approach has limited efficacy in patients without any mutations in the genes included in the panel. In conclusion, we identified a reliable and easy-to-use approach for a simplified molecular-based stratification of mCRC patients that predicts the efficacy of the first-line conventional combination therapy

Updated Italian Tetrapod Ichnology Reference List

We provide a list of contribution by Italian scientists to tetrapod ichnology with papers on both material from Italy and abroad. Foreign author’s contributions on tetrapod ichnology based on material from Italy are also considered. The list updates the previous one published by D’Orazi Porchetti et al. (2008) and, as a result, includes works from 1869 up to now. Following the previous reference list, papers of non-Italian researchers on foreign material are reported when the material was found on Italian territory at the time of publication