An Industrial Application of Business Intelligence Approach to the Electronic Defence Sector

In the age of digital transformation, the availability of data is growing ex-ponentially leading companies to struggle in processing big data while not missing out useful insights to focus on their business development strate-gy. In this scenario, always more often companies are making use of Busi-ness Intelligence platforms that could allow them to collect, analyses and disseminate data in real time to face the dynamic of the market. This paper aims to apply a Business Intelligence approach that adopts OSINT (open-source intelligence) and SOCMINT (Social Media Intelligence) techniques to Defence Electronics Market to analyse how this technology could facili-tate Companies decision-making process by providing them with a distinct competitive advantage. In this frame we used QUIPO intelligence platform for an industrial scenario analysis in the Defence Electronics sector. This is an initial research to study the correlation between the experimental OSINT analysis carried out by the intelligence platform and the information based on the internal experience and know-how of the company for the use case study

Pathogenesis of Autoimmune Cytopenias in Inborn Errors of Immunity Revealing Novel Therapeutic Targets

Autoimmune diseases are usually associated with environmental triggers and genetic predisposition. However, a few number of autoimmune diseases has a monogenic cause, mostly in children. These diseases may be the expression, isolated or associated with other symptoms, of an underlying inborn error of immunity (IEI). Autoimmune cytopenias (AICs), including immune thrombocytopenic purpura (ITP), autoimmune hemolytic anemia (AIHA), autoimmune neutropenia (AN), and Evans' syndrome (ES) are common presentations of immunological diseases in the pediatric age, with at least 65% of cases of ES genetically determined. Autoimmune cytopenias in IEI have often a more severe, chronic, and relapsing course. Treatment refractoriness also characterizes autoimmune cytopenia with a monogenic cause, such as IEI. The mechanisms underlying autoimmune cytopenias in IEI include cellular or humoral autoimmunity, immune dysregulation in cases of hemophagocytosis or lymphoproliferation with or without splenic sequestration, bone marrow failure, myelodysplasia, or secondary myelosuppression. Genetic characterization of autoimmune cytopenias is of fundamental importance as an early diagnosis improves the outcome and allows the setting up of a targeted therapy, such as CTLA-4 IgG fusion protein (Abatacept), small molecule inhibitors (JAK-inhibitors), or gene therapy. Currently, gene therapy represents one of the most attractive targeted therapeutic approaches to treat selected inborn errors of immunity. Even in the absence of specific targeted therapies, however, whole exome genetic testing (WES) for children with chronic multilineage cytopenias should be considered as an early diagnostic tool for disease diagnosis and genetic counseling

COVID-19 in Infants Less than 3 Months: Severe or Not Severe Disease?

Compared to adults, severe or fatal COVID-19 disease is much less common in children. However, a higher risk for progression has been reported in infants. Different pediatric COVID-19 severity scores are reported in the literature

Increased Bone Marrow Interleukin-7 (IL-7)/IL-7R Levels but Reduced IL-7 Responsiveness in HIV-Positive Patients Lacking CD4+ Gain on Antiviral Therapy

Background: The bone marrow (BM) cytokine milieu might substantially affect T-lymphocyte homeostasis in HIV-positive individuals. Interleukin-7 (IL-7) is a bone marrow-derived cytokine regulating T-cell homeostasis through a CD4+-driven feedback loop. CD4+ T-lymphopenia is associated with increased free IL-7 levels and reduced IL-7R expression/function, which are only partially reverted by highly active antiretroviral therapy (HAART). We investigated the BM production, peripheral expression and signaling (pStat5+ and Bcl-2+ CD4+/CD8+ T cells) of IL-7/IL-7Ra in 30 HAART-treated HIV-positive patients who did not experience CD4+ recovery (CD4+ #200/ml) and who had different levels of HIV viremia; these patients included 18 immunological nonresponders (INRs; HIV-RNA#50), 12 complete failures (CFs; HIV-RNA.1000), and 23 HIVseronegative subjects. Methods: We studied plasma IL-7 levels, IL-7Ra+CD4+/CD8+ T-cell proportions, IL-7Ra mRNA expression in PBMCs, spontaneous IL-7 production by BM mononuclear cells (BMMCs), and IL-7 mRNA/IL-7Ra mRNA in BMMC-derived stromal cells (SCs). We also studied T-cell responsiveness to IL-7 by measuring the proportions of pStat5+ and Bcl-2+ CD4+/CD8+ T cells. Results: Compared to HIV-seronegative controls, CFs and INRs presented elevated plasma IL-7 levels and lower IL-7Ra CD4+/CD8+ cell-surface expression and peripheral blood production, confirming the most relevant IL-7/IL-7R disruption. Interestingly, BM investigation revealed a trend of higher spontaneous IL-7 production in INRs (p = .09 vs. CFs) with a nonsignificant trend toward higher IL-7-Ra mRNA levels in BMMC-derived stromal cells. However, upon IL-7 stimulation, the proportion of pStat5+CD4+ T cells did not increase in INRs despite higher constitutive levels (p = .06); INRs also displayed lower Bcl-2+CD8+ T-cell proportions than controls (p = .04). Conclusions: Despite severe CD4+ T-lymphopenia and a disrupted IL-7/IL-7R profile in the periphery, INRs display elevated BM IL-7/IL-7Ra expression but impaired T-cell responsiveness to IL-7, suggesting the activity of a central compensatory pathway targeted to replenish the CD4+ compartment, which is nevertheless inappropriate to compensate the dysfunctional signaling through IL-7 receptor

Comparative Proteomic Analysis of Serum from Patients with Systemic Sclerosis and Sclerodermatous GVHD. Evidence of Defective Function of Factor H

BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease characterized by immunological and vascular abnormalities. Until now, the cause of SSc remains unclear. Sclerodermatous graft-versus-host disease (ScGVHD) is one of the most severe complications following bone marrow transplantation (BMT) for haematological disorders. Since the first cases, the similarity of ScGVHD to SSc has been reported. However, both diseases could have different etiopathogeneses. The objective of this study was to identify new serum biomarkers involved in SSc and ScGVHD. METHODOLOGY: Serum was obtained from patients with SSc and ScGVHD, patients without ScGVHD who received BMT for haematological disorders and healthy controls. Bi-dimensional electrophoresis (2D) was carried out to generate maps of serum proteins from patients and controls. The 2D maps underwent image analysis and differently expressed proteins were identified. Immuno-blot analysis and ELISA assay were used to validate the proteomic data. Hemolytic assay with sheep erythrocytes was performed to evaluate the capacity of Factor H (FH) to control complement activation on the cellular surface. FH binding to endothelial cells (ECs) was also analysed in order to assess possible dysfunctions of this protein. PRINCIPAL FINDINGS: Fourteen differentially expressed proteins were identified. We detected pneumococcal antibody cross-reacting with double stranded DNA in serum of all bone marrow transplanted patients with ScGVHD. We documented higher levels of FH in serum of SSc and ScGVHD patients compared healthy controls and increased sheep erythrocytes lysis after incubation with serum of diffuse SSc patients. In addition, we observed that FH binding to ECs was reduced when we used serum from these patients. CONCLUSIONS: The comparative proteomic analysis of serum from SSc and ScGVHD patients highlighted proteins involved in either promoting or maintaining an inflammatory state. We also found a defective function of Factor H, possibly associated with ECs damage

Vaccination in immunocompromised host: Recommendations of Italian Primary Immunodeficiency Network Centers (IPINET)

Infectious complications are a major cause of morbidity and mortality in patients with primary or secondary immunodeficiency. Prevention of infectious diseases by vaccines is among the most effective healthcare measures mainly for these subjects. However immunocompromised people vary in their degree of immunosuppression and susceptibility to infection and, therefore, represent a heterogeneous population with regard to immunization. To date there is no well- established evidence for use of vaccines in immunodeficient patients, and indications are not clearly defined even in high-quality reviews and in most of the guidelines prepared to provide recommendations for the active vaccination of immunocompromised hosts. The aim of this document is to issue recommendations based on published literature and the collective experience of the Italian primary immunodeficiency centers, about how and when vaccines can be used in immunocompromised patients, in order to facilitate physician decisions and to ensure the best immune protection with the lowest risk to the health of the patient

Interleukin-15 Activates Proinflammatory and Antimicrobial Functions in Polymorphonuclear Cells

Interleukin-15 (IL-15) is a recently discovered cytokine produced by a wide range of different cell types including fibroblasts, keratinocytes, endothelial cells, and macrophages in response to lipopolysaccharide or microbial infection. This suggests that IL-15 may play a crucial role in the activation of phagocytic cells against pathogens. We studied polymorphonuclear leukocyte (PMN) activation by IL-15, evaluated as enhancement of PMN anti-Candida activity as well as IL-8 production, following stimulation with the cytokine. The PMN response to IL-15 depends on binding to the IL-15 receptor. Our experiments show that binding of a biotinylated human IL-15–immunoglobulin G2b IgG2b fusion protein was competed by the addition of human recombinant IL-15 (rIL-15) or of human rIL-2, suggesting that IL-15 binding to PMN might involve the IL-2Rβ and IL-2Rγ chains, which have been shown to be constitutively expressed by PMN. In addition, we show by reverse transcription-PCR and by flow cytometry with a specific anti-IL-15Rα chain monoclonal antibody that PMN express the IL-15Rα chain at the mRNA and protein levels. Incubation with IL-15 activated PMN to secrete the chemotactic factor IL-8, and the amount secreted was increased by costimulation with heat-inactivated Candida albicans. In addition, IL-15 primed the metabolic burst of PMN in response to formyl-methionyl-leucyl-phenylalanine but was not sufficient to trigger the respiratory burst or to increase the production of superoxide in PMN exposed to C. albicans. IL-15 also increased the ability of PMN to phagocytose heat-killed C. albicans organisms in a dose-dependent manner, without opsonization by antibodies or complement-derived products. In the same concentration range, IL-15 was as effective as gamma interferon (IFN-γ) and IL-2 in increasing the C. albicans growth-inhibitory activity of PMN. Taken together, these results suggest that IL-15 is a potent stimulant of both proinflammatory and antifungal activities of PMN, activating several antimicrobial functions of PMN involved in the cellular response against C. albicans

Perinatally HIV-Infected Youths After Transition from Pediatric to Adult Care, a Single-Center Experience from Northern Italy

With the development of combination antiretroviral therapy (cART), the first generation of perinatally HIV-infected children has reached young adulthood. A retrospective study was conducted on perinatally HIV-infected young adults after transition to adult care in Brescia (Northern Italy). Twenty-four patients were transferred to Infectious Disease outpatient Clinic from Pediatric Clinic between 2004 and 2016. Median age at transition was 18 years. 37.5% were male, and 75% were Italian. Median CD4+ T-cell count was 534 cell/μL, and 9/24 presented detectable HIV-RNA at the time of transition. At month 12 after transition, median CD4+ T-cell count was 626 cell/μL, and HIV-RNA was still detectable in 25% of patients. Nineteen patients were still in care at the end of follow-up (median of 52 months); 100% on cART, with undetectable HIV-RNA and a median CD4+ T-cell count of 716 cell/μL. After transition, cART regimen was modified in 14/19 patients (in 13 of them it was modified at least twice). Resistance testing is available for 13 patients showing resistance-associated mutations to at least one class of drugs in 9 patients. Transition to adult care is a critical point and youths present lower rates of viral suppression compared to adults. We observed 80% of viral suppression (5 young patients were lost to follow-up and considered as failures), notwithstanding social problems and resistance mutations. With the availability of more potent and better-tolerated drugs, optimization of cART is possible also in this previously difficult-to-treat group of patients. Novel tools to address adherence to cART in young adults and teenagers will also be needed