Artificial Intelligence Algorithms in Precision Medicine: A New Approach in Clinical Decision-Making

US National Institutes of Health described the precision medicine as ‘an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment and lifestyle for each person.’ In other words, on the basis of the definition, the precision medicine allows to treat patients based on their genetic, lifestyle, and environmental data. Nevertheless, the complexity and rise of data in healthcare arising from cheap genome sequencing, advanced biotechnology, health sensors patients use at home, and the collection of information about patients’ journey in healthcare with hand-held devices unquestionably require a suitable toolkit and advanced analytics for processing the huge information. The artificial intelligence algorithms (AI) can remarkably improve the ability to use big data to make predictions by reducing the cost of making predictions. The advantages of artificial intelligence algorithms have been extensively discussed in the medical literature. In this paper based on the collection of the data relevant for the health of a given individual and the inference obtained by AI, we provide a simulation environment for understanding and suggesting the best actions that need to be performed to improve the individual’s health. Such simulation modelling can help improve clinical decision-maing and the fundamental understanding of the healthcare system and clinical process

Novel Anticancer Drug 5H-pyro[3,2-a] Phenoxazin-5-one (PPH) Regulates lncRNA HOTAIR and HOXC genes in Human MCF-7 Cells

Breast cancer in women is the second most commonly cancer, after skin cancer. The percentage of mortalityrisk for breast cancer is 1 in 37 women (2.7%), which makes breast cancer represent the second cause of cancerdeath in women. Recently, new research based on previously published work in systemic chemotherapy andendocrine therapy field, have improved the incidence rates. The quinonic nucleus is common to many naturaland synthetic products associated with anticancer and antibacterial activities, these compounds are typicallyDNA-intercalating agents. The Class I Homeobox genes (HOX in human and hox in mouse) control embryonicdevelopment and specific determination of positional identity anteroposterior axis of the human body. The HOXgenes, are 39 transcription factors related to morphological, physiological disease. It has been demonstratedthat any deregulation into the network is able to induce neoplastic transformation. Particularly, HOXC locuscollaborating with lncRNA HOTAIR play a key role in breast cancer. In this study, our group evaluated the chemical and metabolic stability of new anticancer molecule 5H-pyro[3,2-a] phenoxazin-5-one (PPH). In a recent paper, we have already demonstrated that a new and potent anticancersynthetic iminoquinone, the 5H-pyrido[3,2-a]phenoxazin-5-one (PPH), is able to inhibit a large number oflymphoblastoid and solid-tumor-derived cells at submicromolar concentrations. Based on our previous research, we decided to analyze the cytotoxic effect and capability of PPH to control thelncRNA HOTAIR and HOXC locus gene expression in human breast cancer cells MCF-7, in order to demonstrateits role like potential new breast cancer antitumor drug

Chemistry meets Industry and Society A creative showcase conference

Buffalo milk contributes to 13% of the world milk production and is abundantly produced in Southern Italy regions. Buffalo milk is appreciated for its nutritive properties and is highly suitable for the manufacturing of wide range of dairy products. Several studies showed many bioactive peptides in different dairy species such as bovine, ovine and caprine milk, but few studies have been conducted on the buffalo dairy products (1). The present work is focused on the identification of bioactive peptides released after in vitro simulated gastrointestinal digestion of protein fraction isolated from buffalo-milk dairy products by ultra- and nanofiltration pilot plant. The gastrointestinal digests of protein fractions were monitored by RP-UHPLC-DAD, while, the peptide identification was carried out by UHPLC-Orbitrap-based tandem mass spectrometry. 165 peptides were identified in Yoghurt, 152 in Scamorza, 146 in Mozzarella, 136 in Grana and Ricotta and 120 in Ice Cream samples (1). The peptides belong to both buffalo caseins (αs1-, β-, k-CN) and whey proteins (α-LA, β-LG). Six G.I. digests of dairy products were tested in a model of oxidative stress using IEC-6 cells. Among them, buffalo ricotta cheese was the most active. UHPLC-PDA-MS/MS analysis revealed the presence of two abundant β-lactoglobulin peptides (BRP: YVEELKPTPEGDL, f:60-72 and BRP2: SFNPTQL, f:168-174). To confirm the hypothesized chemical structures and study their specific biological activity, the peptides were synthesized by conventional solid-phase peptide synthesis methods. The antioxidant potential of the identified peptides was then evaluated in a model of hydrogen peroxide induced oxidative stress in IEC-6 cell line. The peptides reduce ROS release and increase nuclear factor (erythroid-derived 2)-like 2 activation and the expression of antioxidant cytoprotective factors such as heme oxygenase 1, NAD(P)H: quinone oxidoreductase 1 and superoxide dismutase (2). The bioavailability of β-lactoglobulin peptides was evaluated in intestinal transport studies through Caco-2 cell monolayer. Only BRP2 showed equal bi-directional transport and linear permeability, suggesting that it was mainly absorbed through passive diffusion. In addition to its local effects, administration of BPR2 on mice mesenteric arteries counteracts the Angiotensin II-induced vasoconstriction by Nrf2 nuclear translocation, reduction of active form of Ras-related C3 botulinum toxin substrate 1 (Rac1) and NADPH oxidase activity. The analysis at molecular level of treated vessels showed an induction of Nrf2 translocation to nucleus associated with increased expression of MnSOD and Rac1 deactivation. The data indicate how protein fraction of buffalo ricotta cheese could be an important source of antioxidant compounds, as well as YVEELKPTPEGDL and SFNPTQL peptides could be considered as an “ingredient” for nutraceuticals formulations and functional and personalized foods, in order to prevent the onset of some gastrointestinal pathologies and cardiovascular diseases

Novel anticancer drug 5h-pyro[3,2-a] phenoxazin-5-one (PPH) regulates lncRNA HOTAIR and HOXC genes in human MCF-7 cells

Breast cancer in women is the second most commonly cancer, after skin cancer. The percentage of mortality risk for breast cancer is 1 in 37 women (2.7%), which makes breast cancer represent the second cause of cancer death in women. Recently, new research based on previously published work in systemic chemotherapy and endocrine therapy field, have improved the incidence rates. The quinonic nucleus is common to many natural and synthetic products associated with anticancer and antibacterial activities, these compounds are typically DNA-intercalating agents. The Class I Homeobox genes (HOX in human and hox in mouse) control embryonic development and specific determination of positional identity anteroposterior axis of the human body. The HOX genes, are 39 transcription factors related to morphological, physiological disease. It has been demonstrated that any deregulation into the network is able to induce neoplastic transformation. Particularly, HOXC locus collaborating with lncRNA HOTAIR play a key role in breast cancer. In this study, our group evaluated the chemical and metabolic stability of new anticancer molecule 5H-pyro[3,2-a] phenoxazin-5-one (PPH). In a recent paper, we have already demonstrated that a new and potent anticancer synthetic iminoquinone, the 5H-pyrido[3,2-a]phenoxazin-5-one (PPH), is able to inhibit a large number of lymphoblastoid and solid-tumor-derived cells at submicromolar concentrations. Based on our previous research, we decided to analyze the cytotoxic effect and capability of PPH to control the lncRNA HOTAIR and HOXC locus gene expression in human breast cancer cells MCF-7, in order to demonstrate its role like potential new breast cancer antitumor drug

Annexin A1 Released in Extracellular Vesicles by Pancreatic Cancer Cells Activates Components of the Tumor Microenvironment, through Interaction with the Formyl-Peptide Receptors

Pancreatic cancer (PC) is one of the most aggressive cancers in the world. Several extracellular factors are involved in its development and metastasis to distant organs. In PC, the protein Annexin A1 (ANXA1) appears to be overexpressed and may be identified as an oncogenic factor, also because it is a component in tumor-deriving extracellular vesicles (EVs). Indeed, these microvesicles are known to nourish the tumor microenvironment. Once we evaluated the autocrine role of ANXA1-containing EVs on PC MIA PaCa-2 cells and their pro-angiogenic action, we investigated the ANXA1 paracrine effect on stromal cells like fibroblasts and endothelial ones. Concerning the analysis of fibroblasts, cell migration/invasion, cytoskeleton remodeling, and the different expression of specific protein markers, all features of the cell switching into myofibroblasts, were assessed after administration of wild type more than ANXA1 Knock-Out EVs. Interestingly, we demonstrated a mechanism by which the ANXA1-EVs complex can stimulate the activation of formyl peptide receptors (FPRs), triggering mesenchymal switches and cell motility on both fibroblasts and endothelial cells. Therefore, we highlighted the importance of ANXA1/EVs-FPR axes in PC progression as a vehicle of intercommunication tumor cells-stroma, suggesting a specific potential prognostic/diagnostic role of ANXA1, whether in soluble form or even if EVs are captured in PC

Bioavailable Citrus sinensis extract: Polyphenolic composition and biological activity

Citrus plants contain large amounts of flavonoids with beneficial effects on human health. In the present study, the antioxidant and anti-inflammatory potential of bioavailable polyphenols from Citrus sinensis was evaluated in vitro and ex vivo, using the murine macrophages cell line J774A.1 and primary peritoneal macrophages. Following simulated gastro-intestinal digestion, the in vitro bioavailability of Citrus sinensis polyphenolic extract was assessed using the human cell line Caco-2 grown as monolayers on a transwell membrane. Data demonstrated a relative permeation of its compounds (8.3%). Thus, the antioxidant and anti-inflammatory effect of polyphenolic Citrus sinensis fraction (Cs) was compared to the bioavailable one (CsB). Results revealed that Citrus extract were able to reduce macrophages pro-inflammatory mediators, including nitric oxide, iNOS, COX-2 and different cytokines. Moreover, the effect of Citrus sinensis polyphenols was associated with antioxidant effects, such as a reduction of reactive oxygen species (ROS) and heme-oxygenase-1 (HO-1) increased expression. Our results provide evidence that the bioavailable polyphenolic constituents of the Citrus sinensis extract accumulate prevalently at intestinal level and could reach systemic circulation exerting their effect. The bioavailable fraction showed a higher anti-inflammatory and antioxidant potential compared to the initial extract, thus highlighting its potential nutraceutical value

Emergent diffeomorphism invariance in a discrete loop quantum gravity model

Several approaches to the dynamics of loop quantum gravity involve discretizing the equations of motion. The resulting discrete theories are known to be problematic since the first class algebra of constraints of the continuum theory becomes second class upon discretization. If one treats the second class constraints properly, the resulting theories have very different dynamics and number of degrees of freedom than those of the continuum theory. It is therefore questionable how these theories could be considered a starting point for quantization and the definition of a continuum theory through a continuum limit. We show explicitly in a model that the {\em uniform discretizations} approach to the quantization of constrained systems overcomes these difficulties. We consider here a simple diffeomorphism invariant one dimensional model and complete the quantization using {\em uniform discretizations}. The model can be viewed as a spherically symmetric reduction of the well known Husain--Kucha\v{r} model of diffeomorphism invariant theory. We show that the correct quantum continuum limit can be satisfactorily constructed for this model. This opens the possibility of treating 1+1 dimensional dynamical situations of great interest in quantum gravity taking into account the full dynamics of the theory and preserving the space-time covariance at a quantum level.Comment: 12 pages, Revte

The volume operator in covariant quantum gravity

A covariant spin-foam formulation of quantum gravity has been recently developed, characterized by a kinematics which appears to match well the one of canonical loop quantum gravity. In particular, the geometrical observable giving the area of a surface has been shown to be the same as the one in loop quantum gravity. Here we discuss the volume observable. We derive the volume operator in the covariant theory, and show that it matches the one of loop quantum gravity, as does the area. We also reconsider the implementation of the constraints that defines the model: we derive in a simple way the boundary Hilbert space of the theory from a suitable form of the classical constraints, and show directly that all constraints vanish weakly on this space.Comment: 10 pages. Version 2: proof extended to gamma > 1

Spinning Loop Black Holes

In this paper we construct four Kerr-like spacetimes starting from the loop black hole Schwarzschild solutions (LBH) and applying the Newman-Janis transformation. In previous papers the Schwarzschild LBH was obtained replacing the Ashtekar connection with holonomies on a particular graph in a minisuperspace approximation which describes the black hole interior. Starting from this solution, we use a Newman-Janis transformation and we specialize to two different and natural complexifications inspired from the complexifications of the Schwarzschild and Reissner-Nordstrom metrics. We show explicitly that the space-times obtained in this way are singularity free and thus there are no naked singularities. We show that the transformation move, if any, the causality violating regions of the Kerr metric far from r=0. We study the space-time structure with particular attention to the horizons shape. We conclude the paper with a discussion on a regular Reissner-Nordstrom black hole derived from the Schwarzschild LBH and then applying again the Newmann-Janis transformation.Comment: 18 pages, 18 figure