Mathematical Modeling of the Gastrointestinal System for Preliminary Drug Absorption Assessment.

The objective of this study is to demonstrate the potential of a multicompartmental mathematical model to simulate the activity of the gastrointestinal system after the intake of drugs, with a limited number of parameters. The gastrointestinal system is divided into five compartments, modeled as both continuous systems with discrete events (stomach and duodenum) and systems with delay (jejunum, ileum, and colon). The dissolution of the drug tablet occurs in the stomach and is described through the Noyes-Whitney equation, with pH dependence expressed through the Henderson-Hasselbach relationship.

Mathematical Modeling of Vedolizumab Treatment's Effect on Microbiota and Intestinal Permeability in Inflammatory Bowel Disease Patients.

Growing evidence suggests that impaired gut permeability and gut microbiota alterations are involved in the pathogenesis of Inflammatory Bowel Diseases (IBDs), which include Ulcerative Colitis (UC) and Crohn's Disease (CD). Vedolizumab is an anti-α4β7 antibody approved for IBD treatment, used as the first treatment or second-line therapy when the first line results in inadequate effectiveness. The aim of this study is to develop a mathematical model capable of describing the pathophysiological mechanisms of Vedolizumab treatment in IBD patients.

Coexisting cancer stem cells with heterogeneous gene amplifications, transcriptional profiles, and malignancy are isolated from single glioblastomas.

Glioblastoma (GBM) is known as an intractable, highly heterogeneous tumor encompassing multiple subclones, each supported by a distinct glioblastoma stem cell (GSC). The contribution of GSC genetic and transcriptional heterogeneity to tumor subclonal properties is debated. In this study, we describe the systematic derivation, propagation, and characterization of multiple distinct GSCs from single, treatment-naive GBMs (GSC families).

MicroRNA 483-3p overexpression unleashes invasive growth of metastatic colorectal cancer via NDRG1 downregulation and ensuing activation of the ERBB3/AKT axis.

In colorectal cancer, the mechanisms underlying tumor aggressiveness require further elucidation. Taking advantage of a large panel of human metastatic colorectal cancer xenografts and matched stem-like cell cultures (m-colospheres), here we show that the overexpression of microRNA 483-3p (miRNA-483-3p; also known as MIR-483-3p), encoded by a frequently amplified gene locus, confers an aggressive phenotype. In m-colospheres, endogenous or ectopic miRNA-483-3p overexpression increased proliferative response, invasiveness, stem cell frequency, and resistance to differentiation.

The unusual first sign of presentation of renal cell carcinoma: a rare case report.

Background: Renal cell carcinoma (RCC) usually is characterized by a slow pattern of growth, although with an unpredictable evolution and metastatic potential, favored by its extensive vascularity and related high angioinvasive profile. The most common sites of metastases from kidney cancer are lung, lymph nodes, bone and liver; whereas orbital metastases are very uncommon. In more than 25% of cases, orbital metastases are the first manifestation of a primary tumor of unknown origin.

The Bradley-Terry Regression Trunk approach for Modeling Preference Data with Small Trees.

This paper introduces the Bradley-Terry regression trunk model, a novel probabilistic approach for the analysis of preference data expressed through paired comparison rankings. In some cases, it may be reasonable to assume that the preferences expressed by individuals depend on their characteristics. Within the framework of tree-based partitioning, we specify a tree-based model estimating the joint effects of subject-specific covariates over and above their main effects.

ERBB3 overexpression due to miR-205 inactivation confers sensitivity to FGF, metabolic activation, and liability to ERBB3 targeting in glioblastoma.

In glioblastoma (GBM), the most frequent and lethal brain tumor, therapies suppressing recurrently altered signaling pathways failed to extend survival. However, in patient subsets, specific genetic lesions can confer sensitivity to targeted agents. By exploiting an integrated model based on patient-derived stem-like cells, faithfully recapitulating the original GBMs in vitro and in vivo, here, we identify a human GBM subset (∼9% of all GBMs) characterized by ERBB3 overexpression and nuclear accumulation.

Cancer of unknown primary stem-like cells model multi-organ metastasis and unveil liability to MEK inhibition.

Cancers of unknown primary (CUPs), featuring metastatic dissemination in the absence of a primary tumor, are a biological enigma and a fatal disease. We propose that CUPs are a distinct, yet unrecognized, pathological entity originating from stem-like cells endowed with peculiar and shared properties. These cells can be isolated in vitro (agnospheres) and propagated in vivo by serial transplantation, displaying high tumorigenicity.

Avoiding Degeneracies in Ordinal Unfolding Using Kemeny-Equivalent Dissimilarities for Two-Way Two-Mode Preference Rank Data.

In this paper a simple but effective procedure to avoid degeneracies in ordinal Unfolding for preference rank data based on the Kemeny distance is proposed. Considering Unfolding as a particular MDS procedure with missing within-set proximities, unknown proximities are first estimated using correlations related to the Kemeny distance, and then the complete proximity matrix is analyzed in a standard MDS framework. A simulation study shows that our proposal is able to both recover the order of the preferences and reproduce the position of both rankings and objects in a geometrical space.

Ovariectomy Impairs Socio-Cognitive Functions in Dogs.

Recent studies have underlined the effect of ovariectomy on the spatial cognition of female dogs, with ovariectomized dogs showing a clear preference for an egocentric rather than an allocentric navigation strategy whereas intact females did not show preferences. Intact females had better performances than gonadectomized females in solving a learning task in a maze. Ovariectomy also affects socio-cognitive abilities, reducing the dog's level of attention on the owner.

Vaccination knowledge and acceptability among pregnant women in Italy.

The aims of this survey were to ascertain pregnant women's level of knowledge and acceptability on the vaccinations and to identify their associations with several characteristics. A cross-sectional study was performed from December 2017 through March 2018 in the geographic area of Naples, Italy. The study used two stages cluster sampling method for selection and recruitment of participants.

Genetic Evolution of Glioblastoma Stem-Like Cells From Primary to Recurrent Tumor.

Glioblastoma (GBM) is a lethal tumor that displays remarkable genetic heterogeneity. It is also known that GBM contains a cell hierarchy driven by GBM stem-like cells (GSCs), responsible for tumor generation, therapeutic resistance, and relapse. An important and still open issue is whether phylogenetically related GSCs can be found in matched primary and recurrent GBMs, and reflect tumor genetic evolution under therapeutic pressure.

A Recursive Partitioning Method for the Prediction of Preference Rankings Based Upon Kemeny Distances.

Preference rankings usually depend on the characteristics of both the individuals judging a set of objects and the objects being judged. This topic has been handled in the literature with log-linear representations of the generalized Bradley-Terry model and, recently, with distance-based tree models for rankings. A limitation of these approaches is that they only work with full rankings or with a pre-specified pattern governing the presence of ties, and/or they are based on quite strict distributional assumptions.

MET inhibition overcomes radiation resistance of glioblastoma stem-like cells.

Glioblastoma (GBM) contains stem-like cells (GSCs) known to be resistant to ionizing radiation and thus responsible for therapeutic failure and rapidly lethal tumor recurrence. It is known that GSC radioresistance relies on efficient activation of the DNA damage response, but the mechanisms linking this response with the stem status are still unclear. Here, we show that the MET receptor kinase, a functional marker of GSCs, is specifically expressed in a subset of radioresistant GSCs and overexpressed in human GBM recurring after radiotherapy.

"Social dangerousness and incurability in schizophrenia": results of an educational intervention for medical and psychology students.

This study explored the influence of an educational intervention addressing common prejudices and scientific evidence about schizophrenia on medical and psychology students' views of this disorder. The intervention--consisting in two three-hour lessons with an interval of a week between--was run at first for medical students and then for psychology students. Participants' views of schizophrenia were assessed at baseline vs.

Differences in views of schizophrenia during medical education: a comparative study of 1st versus 5th-6th year Italian medical students.

Purpose: This study explored medical students' causal explanations and views of schizophrenia, and whether they changed during medical education.

Method: The survey was carried out on medical students of the Second University of Naples, Italy, who attended their first-year and their fifth- or sixth-year of lessons. The 381 who accepted were asked to read a case-vignette describing a person who met the ICD-10 criteria for schizophrenia and then fill in the Opinions on mental illness Questionnaire.

Analysis of powered two-wheeler crashes in Italy by classification trees and rules discovery.

Aim of the study was the analysis of powered two-wheeler (PTW) crashes in Italy in order to detect interdependence as well as dissimilarities among crash characteristics and provide insights for the development of safety improvement strategies focused on PTWs. At this aim, data mining techniques were used to analyze the data relative to the 254,575 crashes involving PTWs occurred in Italy in the period 2006-2008. Classification trees analysis and rules discovery were performed.

The MET oncogene is a functional marker of a glioblastoma stem cell subtype.

The existence of treatment-resistant cancer stem cells contributes to the aggressive phenotype of glioblastoma. However, the molecular alterations that drive stem cell proliferation in these tumors remain unknown. In this study, we found that expression of the MET oncogene was associated with neurospheres expressing the gene signature of mesenchymal and proneural subtypes of glioblastoma.

Simulator evaluation of drivers' speed, deceleration and lateral position at rural intersections in relation to different perceptual cues.

Aim of the study was to investigate, by means of a driving simulator experiment, drivers' behaviour in terms of speed, deceleration, and lateral position on major approaches of rural intersections in relation to different perceptual cues. In the experiment, ten different design conditions with and without speed-reducing treatments along the approach to the intersection were tested. Twenty-three drivers drove a test route two times and data from the second drive were used for comparison.

The influence of causal explanations and diagnostic labeling on medical students' views of schizophrenia.

Purpose: Negative attitudes toward mental illness among medical professionals can influence the quality of medical care they provide. The authors examined the impact of causal explanations and diagnostic labeling on medical students' views of schizophrenia.

Method: Medical students in their fifth and sixth years at the Second University of Naples (Italy) who attended lectures from April through June 2010 completed a self-report questionnaire regarding their beliefs about the mental disorder described (but not named) in a case vignette depicting a person who meets the International Classification of Diseases-10 criteria for schizophrenia.

Traffic calming along rural highways crossing small urban communities: driving simulator experiment.

The paper investigated drivers' speed behaviour in a section of a rural highway crossing a small urban community in the existing scenario without any traffic calming device and in two different design scenarios with traffic calming in the urban community. Two gateways and four integrative traffic calming devices along the route within the urban area were tested. The gateways were aimed at slowing down the vehicles entering in the built-up area, while the traffic calming devices were aimed at complementing the gateway effect inside the built-up area.