Acute Promyelocytic Leukemia in Children: A Model of Precision Medicine and Chemotherapy-Free Therapy

Acute promyelocytic leukemia (APL) represents a paradigm of precision medicine. Indeed, in the last decades, the introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) completely revolutionized the therapeutic approach to this previously highly fatal disorder. This entirely chemotherapy-free treatment, which provided excellent survival rates, has been initially validated in adults and, recently, translated in the pediatric setting. This review summarizes currently available data on the use of ATRA and ATO combination in pediatric APL, providing a particular focus on peculiar issues and challenges, such as the occurrence of pseudotumor cerebri and death during induction (early death), as well as the advantage offered by the ATO/ATRA combination in sparing long-term sequelae.     

Pulsed Electromagnetic Field Stimulation in Osteogenesis and Chondrogenesis: Signaling Pathways and Therapeutic Implications

Mesenchymal stem cells (MSCs) are the main cell players in tissue repair and thanks to their self-renewal and multi-lineage differentiation capabilities, they gained significant attention as cell source for tissue engineering (TE) approaches aimed at restoring bone and cartilage defects. Despite significant progress, their therapeutic application remains debated: the TE construct often fails to completely restore the biomechanical properties of the native tissue, leading to poor clinical outcomes in the long term. Pulsed electromagnetic fields (PEMFs) are currently used as a safe and non-invasive treatment to enhance bone healing and to provide joint protection. PEMFs enhance both osteogenic and chondrogenic differentiation of MSCs. Here, we provide extensive review of the signaling pathways modulated by PEMFs during MSCs osteogenic and chondrogenic differentiation. Particular attention has been given to the PEMF-mediated activation of the adenosine signaling and their regulation of the inflammatory response as key player in TE approaches. Overall, the application of PEMFs in tissue repair is foreseen: (1) in vitro: to improve the functional and mechanical properties of the engineered construct; (2) in vivo: (i) to favor graft integration, (ii) to control the local inflammatory response, and (iii) to foster tissue repair from both implanted and resident MSCs cells.     

Complementary Effects of Carbamylated and Citrullinated LL37 in Autoimmunity and Inflammation in Systemic Lupus Erythematosus

LL37 acts as T-cell/B-cell autoantigen in Systemic lupus erythematosus (SLE) and psoriatic disease. Moreover, when bound to “self” nucleic acids, LL37 acts as “danger signal,” leading to type I interferon (IFN-I)/pro-inflammatory factors production. T-cell epitopes derived from citrullinated-LL37 act as better antigens than unmodified LL37 epitopes in SLE, at least in selected HLA-backgrounds, included the SLE-associated HLA-DRB1*1501/HLA-DRB5*0101 backgrounds. Remarkably, while “fully-citrullinated” LL37 acts as better T-cell-stimulator, it loses DNA-binding ability and the associated “adjuvant-like” properties. Since LL37 undergoes a further irreversible post-translational modification, carbamylation and antibodies to carbamylated self-proteins other than LL37 are present in SLE, here we addressed the involvement of carbamylated-LL37 in autoimmunity and inflammation in SLE. We detected carbamylated-LL37 in SLE-affected tissues. Most importantly, carbamylated-LL37-specific antibodies and CD4 T-cells circulate in SLE and both correlate with disease activity. In contrast to “fully citrullinated-LL37,” “fully carbamylated-LL37” maintains both innate and adaptive immune-cells’ stimulatory abilities: in complex with DNA, carbamylated-LL37 stimulates plasmacytoid dendritic cell IFN-α production and B-cell maturation into plasma cells. Thus, we report a further example of how different post-translational modifications of a self-antigen exert complementary effects that sustain autoimmunity and inflammation, respectively. These data also show that T/B-cell responses to carbamylated-LL37 represent novel SLE disease biomarkers.     

On the Spatial Distribution of Fingerprint Singularities

Fingerprint singularities play an important role in several fingerprint recognition and classification systems. Although some general relationships and constraints about the location of singularities in the different fingerprint classes are well known, to the best of our knowledge no statistical models have been developed until now. This paper studies the spatial distributions of singularity locations in nature and derives, from a representative dataset of labelled samples, the probability density functions of the four main fingerprint classes. The results obtained can be directly exploited to improve the accuracy of many techniques relying on the position of singularities, as confirmed by the results of two experiments on fingerprint classification and synthesis.     

Prognostic normative reasoning

Human users planning for multiple objectives in complex environments are subjected to high levels of cognitive workload, which can severely impair the quality of the plans created. This paper describes a software agent that can proactively assist cognitively overloaded users by providing normative reasoning about prohibitions and obligations so that the user can focus on her primary objectives. In order to provide proactive assistance, we develop the notion of prognostic normative reasoning (PNR) that consists of the following steps: (1) recognizing the user's planned activities, (2) reasoning about norms to evaluate those predicted activities, and (3) providing necessary assistance so that the user's activities are consistent with norms. The idea of PNR integrates various AI techniques, namely, user intention recognition, normative reasoning over a user's intention, and planning, execution and replanning for assistive actions. In this paper, we describe an agent architecture for PNR and discuss practical applications.     

Viral diffusion of technology products: a comprehensive stage framework

Information Systems and e-Business Management - The level of viral diffusion expected after a technology product or service is launched is important for determining the marketing budget,...     

Minutia Cylinder-Code: a new representation and matching technique for fingerprint recognition

In this paper, we introduce the Minutia Cylinder-Code (MCC): a novel representation based on 3D data structures (called cylinders), built from minutiae distances and angles. The cylinders can be created starting from a subset of the mandatory features (minutiae position and direction) defined by standards like ISO/IEC 19794-2 (2005). Thanks to the cylinder invariance, fixed-length, and bit-oriented coding, some simple but very effective metrics can be defined to compute local similarities and to consolidate them into a global score. Extensive experiments over FVC2006 databases prove the superiority of MCC with respect to three well-known techniques and demonstrate the feasibility of obtaining a very effective (and interoperable) fingerprint recognition implementation for light architectures.     

Incidental sadness biases social economic decisions in the Ultimatum Game.

Recent dual-process models of decision making have suggested that emotion plays an important role in decision making; however, the impact of incidental moods (i.e., emotions unrelated to the immediate situation) on decisions remains poorly explored. This question was investigated by inducing 2 basic emotional states (amusement or sadness) that were compared with a neutral-emotion control group. Decision making was assessed with a well-studied social task, the Ultimatum Game. In this task, participants had to make decisions to either accept or reject monetary offers from other players, offers that varied in their degree of unfairness. Emotion was induced with short movie clips. Induced sadness interacted with offer fairness, with higher sadness resulting in lower acceptance rates of unfair offers. Induced amusement was not associated with any significant biases in decision making. These results demonstrate that even subtle incidental moods can play an important role in biasing decision making. Implications of these results in regards to the emotion, cognitive neuroscience, and clinical literatures are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)