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

Transient Decrease of Circulating and Tissular Dendritic Cells in Patients With Mycobacterial Disease and With Partial Dominant IFN\u3b3R1 Deficiency

Interferon-\u3b3 receptor 1 (IFN\u3b3R1) deficiency is one of the inborn errors of IFN-\u3b3 immunity underlying Mendelian Susceptibility to Mycobacterial Disease (MSMD). This molecular circuit plays a crucial role in regulating the interaction between dendritic cells (DCs) and T lymphocytes, thus affecting DCs activation, maturation, and priming of T cells involved in the immune response against intracellular pathogens. We studied a girl who developed at the age of 2.5 years a Mycobacterium avium infection characterized by disseminated necrotizing granulomatous lymphadenitis, and we compared her findings with other patients with the same genetic condition. The patient carried a heterozygous 818del4 mutation in the IFNGR1 gene responsible of autosomal dominant (AD) partial IFN\u3b3R1 deficiency. During the acute infection blood cells immunophenotyping showed a marked reduction in DCs counts, including both myeloid (mDCs) and plasmacytoid (pDCs) subsets, that reversed after successful prolonged antimicrobial therapy. Histology of her abdomen lymph node revealed a profound depletion of tissue pDCs, as compared to other age-matched granulomatous lymphadenitis of mycobacterial origin. Circulating DCs depletion was also observed in another patient with AD partial IFN\u3b3R1 deficiency during mycobacterial infection. To conclude, AD partial IFN\u3b3R1 deficiency can be associated with a transient decrease in both circulating and tissular DCs during acute mycobacterial infection, suggesting that DCs counts monitoring might constitute a useful marker of treatment response

Increased use of high-flow nasal cannulas after the pandemic in bronchiolitis: a more severe disease or a changed physician's attitude?

After the SARS-CoV-2 pandemic, we noticed a marked increase in high-flow nasal cannula use for bronchiolitis. This study aims to report the percentage of children treated with high-flow nasal cannula (HFNC) in various seasons. The secondary outcomes were admissions for bronchiolitis, virological results, hospital burden, and NICU/PICU need. We conducted a retrospective study in four Italian hospitals, examining the medical records of all infants (< 12 months) hospitalized for bronchiolitis in the last four winter seasons (1 September-31 March 2018-2022). In the 2021-2022 winter season, 66% of admitted children received HFNC versus 23%, 38%, and 35% in the previous 3 years. A total of 876 patients were hospitalized in the study periods. In 2021-2022, 300 infants were hospitalized for bronchiolitis, 22 in 2020-2021, 259 in 2019-2020, and 295 in 2018-2019. The percentage of patients needing intensive care varied from 28.7% to 18%, 22%, and 15% in each of the four considered periods (p < 0.05). Seventy-seven percent of children received oxygen in the 2021-2022 winter; vs 50%, 63%, and 55% (p < 0.01) in the previous 3 years. NIV/CPAP was used in 23%, 9%, 16%, and 12%, respectively. In 2021-2020, 2% of patients were intubated; 0 in 2020-2021, 3% in 2019-2020, and 1% in 2018-2019

Multisystem autoimmune disease caused by increased STAT3 phosphorylation, and dysregulated gene expression

Signal transducer and activator of transcription (STAT) 3 is a member of the STAT family, and plays a major role in various immunological mechanisms.1 Mutations in STAT3 are associated with a broad spectrum of manifestations, including immunodeficiency, autoimmunity, and malignancy.2 In particular, heterozygous germline loss-of-function (LOF) mutations cause Hyper-IgE syndrome (HIES),3–5 while heterozygous germline gain-of-function (GOF) mutations have recently been associated to multi-organ autoimmune manifestations (i.e. type 1 diabetes, enteropathy, cytopenia, interstitial lung disease, hypothyroidism), lymphoproliferation, short stature, and recurrent infections (OMIM #615952).6–8 We report a 7-year-old boy who presented with early-onset severe enteropathy, and diffuse eczematous dermatitis since birth. During the first weeks of life, Hirschsprung disease was also suspected and surgically treated. Gastrointestinal and cutaneous manifestations were first ascribed to food allergy with quite a good response to amino acid-based formula. In the following months, the patient failed to thrive, and developed respiratory tract infections. At two years, the patient presented with progressive interstitial lung disease characterized by lymphocytic interstitial infiltration leading to pulmonary hypertension, tricuspid insufficiency, and right ventricular heart failure with hepatomegaly. Because of the increased risk of infections, he received intravenous (IV) immunoglobulin infusions (400 mg/kg), prophylaxis with cotrimoxazole and fluconazole. Methylprednisolone at 0.3 mg/kg/day was also given to treat autoimmune manifestations

The Inborn Errors of Immunity-Virtual Consultation System Platform in Service for the Italian Primary Immunodeficiency Network: Results from the Validation Phase

Purpose: Inborn errors of immunity (IEI) represent a heterogeneous group of rare genetically determined diseases. In some cases, patients present with complex or atypical phenotypes, not fulfilling the accepted diagnostic criteria for IEI and, thus, at high risk of misdiagnosis or diagnostic delay. This study aimed to validate a platform that, through the opinion of immunologist experts, improves the diagnostic process and the level of care of patients with atypical/complex IEI. Methods: Here, we describe the functioning of the IEI-Virtual Consultation System (VCS), an innovative platform created by the Italian Immunodeficiency Network (IPINet). Results: In the validation phase, from January 2020 to June 2021, 68 cases were entered on the IEI-VCS platform. A final diagnosis was achieved in 35/68 cases (51%, 95% CI 38.7 to 64.2). In 22 out of 35 solved cases, the diagnosis was confirmed by genetic analysis. In 3/35 cases, a diagnosis of secondary immunodeficiency was made. In the remaining 10 cases, an unequivocal clinical and immunological diagnosis was obtained, even though not substantiated by genetic analysis. Conclusion: From our preliminary study, the VCS represents an innovative and useful system to improve the diagnostic process of patients with complex unsolved IEI disorders, with benefits both in terms of reduction of time of diagnosis and access to the required therapies. These results may help the functioning of other international platforms for the management of complex cases

Hepatitis B Surface Antigen Seropositive Men in Serodiscordant Couples: Effects on the Assisted Reproductive Outcomes

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Impaired natural killer cell functions in patients with signal transducer and activator of transcription 1 (STAT1) gain-of-function mutations

Gain-of-function (GOF) mutations affecting the coiled-coil domain or the DNA-binding domain of signal transducer and activator of transcription 1 (STAT1) cause chronic mucocutaneous candidiasis disease. This condition is characterized by fungal and bacterial infections caused by impaired generation of TH17 cells; meanwhile, some patients with chronic mucocutaneous candidiasis disease might also have viral or intracellular pathogen infections

Reduced probability of improving viro-immunological state in subjects with vertical transmission of HIV reaching adult age: A multicenter retrospective cohort study

Introduction: Young adults with vertical transmission (VT) of human immunodeficiency virus&nbsp;(HIV) represent a fragile population. This study evaluates factors associated with viro-immunological outcome of these patients. Methods: We performed a multicenter study including HIV-infected subjects with VT ≥ 18 years old from six Italian clinics. Subjects were observed from birth to death, lost to follow-up, or last visit until December 31, 2019. Condition of "optimal viro-immunological status" (OS) was defined as the simultaneous presence of HIV&nbsp;ribonucleic acid&nbsp;(RNA) &lt; 50 copies/mL, CD4+ &gt; 500 cells/mm3 , and CD4+/CD8+ ratio ≥ 1. Results: A total of 126 subjects were enrolled. At 18 years of age, 52/126 (44.4%) had HIV-RNA &gt; 50 copies/mL, 47/126 (38.2%) had CD4+ &lt; 500/mm3 , and 78/126 (67.2%) had&nbsp;CD4+/CD8+ &lt; 1; 28 subjects (23.7%) presented in the condition of OS. Having a CD4+/CD8+ ratio ≥ 1 at 18 years of age was related with an increased probability of shift from suboptimal viro-immunological status (SOS) to OS (HR: 7.7, 95% confidence interval [CI]: 4.23-14.04), and a reduced risk of shift from the OS to the SOS (HR: 0.49, 95% CI: 0.26-0.92). Acquired immunodeficiency syndrome (AIDS) diagnosis significantly reduced the probability of shift from a viro-immunological SOS to OS (HR: 0.09, 95% CI:&nbsp;0.03-0.30). Subjects who had not achieved an OS at 18 years of age had an increased risk of discontinuation of combination antiretroviral therapy (cART, p = .019). Conclusions: Only a small proportion of subjects with VT of HIV reached the adult age with "OS".&nbsp;Transition to the adult care with a compromised viro-immunological condition represents a negative driver for future optimal infection control, with a higher risk of discontinuation of cART and a reduced probability to improve the immunological status later in the years

Increased bronchiolitis burden and severity after the pandemic: a national multicentric study

Background: The coronavirus 2019 (COVID-19) related containment measures led to the disruption of all virus distribution. Bronchiolitis-related hospitalizations shrank during 2020-2021, rebounding to pre-pandemic numbers the following year. This study aims to describe the trend in bronchiolitis-related hospitalization this year, focusing on severity and viral epidemiology. Methods: We conducted a retrospective investigation collecting clinical records data from all infants hospitalized for bronchiolitis during winter (1st September-31th March) from September 2018 to March 2023 in six Italian hospitals. No trial registration was necessary according to authorization no.9/2014 of the Italian law. Results: Nine hundred fifty-three infants were hospitalized for bronchiolitis this last winter, 563 in 2021-2022, 34 in 2020-2021, 395 in 2019-2020 and 483 in 2018-2019. The mean length of stay was significantly longer this year compared to all previous years (mean 7.2 ± 6 days in 2022-2023), compared to 5.7 ± 4 in 2021-2022, 5.3 ± 4 in 2020-2021, 6.4 ± 5 in 2019-2020 and 5.5 ± 4 in 2018-2019 (p < 0.001), respectively. More patients required mechanical ventilation this winter 38 (4%), compared to 6 (1%) in 2021-2022, 0 in 2020-2021, 11 (2%) in 2019-2020 and 6 (1%) in 2018-2019 (p < 0.05), respectively. High-flow nasal cannula and non-invasive respiratory supports were statistically more common last winter (p = 0.001 or less). RSV prevalence and distribution did not differ this winter, but coinfections were more prevalent 307 (42%), 138 (31%) in 2021-2022, 1 (33%) in 2020-2021, 68 (23%) in 2019-2020, 61 (28%) in 2018-2019 (p = 0.001). Conclusions: This study shows a growth of nearly 70% in hospitalisations for bronchiolitis, and an increase in invasive respiratory support and coinfections, suggesting a more severe disease course this winter compared to the last five years