PRILJ: an efficient two-step method based on embedding and clustering for the identification of regularities in legal case judgments

In an era characterized by fast technological progress that introduces new unpredictable scenarios every day, working in the law field may appear very difficult, if not supported by the right tools. In this respect, some systems based on Artificial Intelligence methods have been proposed in the literature, to support several tasks in the legal sector. Following this line of research, in this paper we propose a novel method, called PRILJ, that identifies paragraph regularities in legal case judgments, to support legal experts during the redaction of legal documents. Methodologically, PRILJ adopts a two-step approach that first groups documents into clusters, according to their semantic content, and then identifies regularities in the paragraphs for each cluster. Embedding-based methods are adopted to properly represent documents and paragraphs into a semantic numerical feature space, and an Approximated Nearest Neighbor Search method is adopted to efficiently retrieve the most similar paragraphs with respect to the paragraphs of a document under preparation. Our extensive experimental evaluation, performed on a real-world dataset provided by EUR-Lex, proves the effectiveness and the efficiency of the proposed method. In particular, its ability of modeling different topics of legal documents, as well as of capturing the semantics of the textual content, appear very beneficial for the considered task, and make PRILJ very robust to the possible presence of noise in the data

Neural Stem Cell Plasticity: Advantages in Therapy for the Injured Central Nervous System

The physiological and pathological properties of the neural germinal stem cell niche have been well-studied in the past 30 years, mainly in animals and within given limits in humans, and knowledge is available for the cyto-architectonic structure, the cellular components, the timing of development and the energetic maintenance of the niche, as well as for the therapeutic potential and the cross talk between neural and immune cells. In recent years we have gained detailed understanding of the potentiality of neural stem cells (NSCs), although we are only beginning to understand their molecular, metabolic, and epigenetic profile in physiopathology and, further, more can be invested to measure quantitatively the activity of those cells, to model in vitro their therapeutic responses or to predict interactions in silico. Information in this direction has been put forward for other organs but is still limited in the complex and very less accessible context of the brain. A comprehensive understanding of the behavior of endogenous NSCs will help to tune or model them toward a desired response in order to treat complex neurodegenerative diseases. NSCs have the ability to modulate multiple cellular functions and exploiting their plasticity might make them into potent and versatile cellular drugs

IL-27, but not IL-35, inhibits neuroinflammation through modulating GM-CSF expression

IL-27 and IL-35 are heterodimeric cytokines, members of the IL-12 family and considered to have immunomodulatory properties. Their role during neuroinflammation had been investigated using mutant mice devoid of either one of their subunits or lacking components of their receptors, yielding conflicting results. We sought to understand the therapeutic potential of IL-27 and IL-35 delivered by gene therapy in neuroinflammation. We constructed lentiviral vectors expressing IL-27 and IL-35 from a single polypeptide chain, and we validated in vitro their biological activity. We injected IL-27 and IL-35-expressing lentiviral vectors into the cerebrospinal fluid (CSF) of mice affected by experimental neuroinflammation (EAE), and performed clinical, neuropathological and immunological analyses. Both cytokines interfere with neuroinflammation, but only IL-27 significantly modulates disease development, both clinically and neuropathologically. IL-27 protects from autoimmune inflammation by inhibiting granulocyte macrophages colony-stimulating factor (GM-CSF) expression in CD4+ T cells and by inducing program death-ligand 1 (PD-L1) expression in both CNS-resident and CNS-infiltrating myeloid cells. We demonstrate here that IL-27 holds therapeutic potential during neuroinflammation and that IL-27 inhibits GM-CSF and induces pd-l1 mRNA in vivo

Infiltrating Blood-Derived Macrophages Are Vital Cells Playing an Anti-inflammatory Role in Recovery from Spinal Cord Injury in Mice

Using a mouse model of spinal injury, Michal Schwartz and colleagues tested the effect of macrophages on the recovery process and demonstrate an important anti-inflammatory role for a subset of infiltrating monocyte-derived macrophages that is dependent upon their expression of interleukin 10

Delayed post-ischaemic neuroprotection following systemic neural stem cell transplantation involves multiple mechanisms

Recent evidence suggests that neural stem/precursor cells (NPCs) promote recovery in animal models with delayed neuronal death via a number of indirect bystander effects. A comprehensive knowledge of how transplanted NPCs exert their therapeutic effects is still lacking. Here, we investigated the effects of a delayed transplantation of adult syngenic NPCs—injected intravenously 72 h after transient middle cerebral artery occlusion—on neurological recovery, histopathology and gene expression. NPC-transplanted mice showed a significantly improved recovery from 18 days post-transplantation (dpt) onwards, which persisted throughout the study. A small percentage of injected NPCs accumulated in the brain, integrating mainly in the infarct boundary zone, where most of the NPCs remained undifferentiated up to 30 dpt. Histopathological analysis revealed a hitherto unreported very delayed neuroprotective effect of NPCs, becoming evident at 10 and 30 dpt. Tissue survival was associated with downregulation of markers of inflammation, glial scar formation and neuronal apoptotic death at both mRNA and protein levels. Our data highlight the relevance of very delayed degenerative processes in the stroke brain that are intimately associated with inflammatory and glial responses. These processes may efficaciously be antagonized by (stem) cell-based strategies at time-points far beyond established therapeutic windows for pharmacological neuroprotectio

Co-Graft of Allogeneic Immune Regulatory Neural Stem Cells (NPC) and Pancreatic Islets Mediates Tolerance, while Inducing NPC-Derived Tumors in Mice

Data available on the immunomodulatory properties of neural stem/precursor cells (NPC) support their possible use as modulators for immune-mediated process. The aim of this study was to define whether NPC administered in combination with pancreatic islets prevents rejection in a fully mismatched allograft model.Diabetic Balb/c mice were co-transplanted under the kidney capsule with pancreatic islets and GFP(+) NPC from fully mismatched C57BL/6 mice. The following 4 groups of recipients were used: mice receiving islets alone; mice receiving islets alone and treated with standard immunosuppression (IL-2Ralpha chain mAbs + FK506 + Rapamycin); mice receiving a mixed islet/NPC graft under the same kidney capsule (Co-NPC-Tx); mice receiving the islet graft under the left kidney capsule and the NPC graft under the right kidney capsule (NPC-Tx). Our results demonstrate that only the co-transplantation and co-localization of NPC and islets (Co-NPC-Tx) induce stable long-term graft function in the absence of immunosuppression. This condition is associated with an expansion of CD4(+)CD25(+)FoxP3(+) T regulatory cells in the spleen. Unfortunately, stable graft function was accompanied by constant and reproducible development of NPC-derived cancer mainly sustained by insulin secretion.These data demonstrate that the use of NPC in combination with islets prevents graft rejection in a fully mismatched model. However, the development of NPC-derived cancer raises serious doubts about the safety of using adult stem cells in combination with insulin-producing cells outside the original microenvironment

Author Correction:Transcriptional dysregulation of Interferome in experimental and human Multiple Sclerosis

The original version of this Article contained a typographical error in the spelling of the author Eliana M Coccia, which was incorrectly given as Eliana Coccia. This has now been corrected in the PDF and HTML versions of the Article, and in the accompanying Supplementary Material files

Persistent Inflammation Alters the Function of the Endogenous Brain Stem Cell Compartment

Endogenous neural stem/precursor cells (NPCs) are considered a functional reservoir for promoting tissue homeostasis and repair after injury, therefore regenerative strategies that mobilize these cells have recently been proposed. Despite evidence of increased neurogenesis upon acute inflammatory insults (e.g. ischaemic stroke), the plasticity of the endogenous brain stem cell compartment in chronic CNS inflammatory disorders remains poorly characterized. Here we show that persistent brain inflammation, induced by immune cells targeting myelin, extensively alters the proliferative and migratory properties of subventricular zone (SVZ)-resident NPCs in vivo leading to significant accumulation of non-migratory neuroblasts within the SVZ germinal niche. In parallel, we demonstrate a quantitative reduction of the putative brain stem cells proliferation in the SVZ during persistent brain inflammation, which is completely reversed after in vitro culture of the isolated NPCs. Together, these data indicate that the inflamed brain microenvironment sustains a non cell-autonomous dysfunction of the endogenous CNS stem cell compartment and challenge the potential efficacy of proposed therapies aimed at mobilizing endogenous precursors in chronic inflammatory brain disorders

Grafted human pluripotent stem cell-derived cortical neurons integrate into adult human cortical neural circuitry

Several neurodegenerative diseases cause loss of cortical neurons, leading to sensory, motor, and cognitive impairments. Studies in different animal models have raised the possibility that transplantation of human cortical neuronal progenitors, generated from pluripotent stem cells, might be developed into a novel therapeutic strategy for disorders affecting cerebral cortex. For example, we have shown that human long-term neuroepithelial-like stem (lt-NES) cell-derived cortical neurons, produced from induced pluripotent stem cells and transplanted into stroke-injured adult rat cortex, improve neurological deficits and establish both afferent and efferent morphological and functional connections with host cortical neurons. So far, all studies with human pluripotent stem cell-derived neurons have been carried out using xenotransplantation in animal models. Whether these neurons can integrate also into adult human brain circuitry is unknown. Here, we show that cortically fated lt-NES cells, which are able to form functional synaptic networks in cell culture, differentiate to mature, layer-specific cortical neurons when transplanted ex vivo onto organotypic cultures of adult human cortex. The grafted neurons are functional and establish both afferent and efferent synapses with adult human cortical neurons in the slices as evidenced by immuno-electron microscopy, rabies virus retrograde monosynaptic tracing, and whole-cell patch-clamp recordings. Our findings provide the first evidence that pluripotent stem cell-derived neurons can integrate into adult host neural networks also in a human-to-human grafting situation, thereby supporting their potential future clinical use to promote recovery by neuronal replacement in the patient's diseased brain