Consensus Middle East and North Africa Registry on Inborn Errors of Immunity

Background: Inborn errors of immunity (IEIs) are a heterogeneous group of genetic defects of immunity, which cause high rates of morbidity and mortality mainly among children due to infectious and non-infectious complications. The IEI burden has been critically underestimated in countries from middle- and low-income regions and the majority of patients with IEI in these regions lack a molecular diagnosis. Methods: We analyzed the clinical, immunologic, and genetic data of IEI patients from 22 countries in the Middle East and North Africa (MENA) region. The data was collected from national registries and diverse databases such as the Asian Pacific Society for Immunodeficiencies (APSID) registry, African Society for Immunodeficiencies (ASID) registry, Jeffrey Modell Foundation (JMF) registry, J Project centers, and International Consortium on Immune Deficiency (ICID) centers. Results: We identified 17,120 patients with IEI, among which females represented 39.4%. Parental consanguinity was present in 60.5% of cases and 27.3% of the patients were from families with a confirmed previous family history of IEI. The median age of patients at the onset of disease was 36 months and the median delay in diagnosis was 41 months. The rate of registered IEI patients ranges between 0.02 and 7.58 per 100,000 population, and the lowest rates were in countries with the highest rates of disability-adjusted life years (DALY) and death rates for children. Predominantly antibody deficiencies were the most frequent IEI entities diagnosed in 41.2% of the cohort. Among 5871 patients genetically evaluated, the diagnostic yield was 83% with the majority (65.2%) having autosomal recessive defects. The mortality rate was the highest in patients with non-syndromic combined immunodeficiency (51.7%, median age: 3.5 years) and particularly in patients with mutations in specific genes associated with this phenotype (RFXANK, RAG1, and IL2RG). Conclusions: This comprehensive registry highlights the importance of a detailed investigation of IEI patients in the MENA region. The high yield of genetic diagnosis of IEI in this region has important implications for prevention, prognosis, treatment, and resource allocation

Detecting Manipulations in Video

This chapter presents the techniques researched and developed within InVID for the forensic analysis of videos, and the detection and localization of forgeries within User-Generated Videos (UGVs). Following an overview of state-of-the-art video tampering detection techniques, we observed that the bulk of current research is mainly dedicated to frame-based tampering analysis or encoding-based inconsistency characterization. We built upon this existing research, by designing forensics filters aimed to highlight any traces left behind by video tampering, with a focus on identifying disruptions in the temporal aspects of a video. As for many other data analysis domains, deep neural networks show very promising results in tampering detection as well. Thus, following the development of a number of analysis filters aimed to help human users in highlighting inconsistencies in video content, we proceeded to develop a deep learning approach aimed to analyze the outputs of these forensics filters and automatically detect tampered videos. In this chapter, we present our survey of the state of the art with respect to its relevance to the goals of InVID, the forensics filters we developed and their potential role in localizing video forgeries, as well as our deep learning approach for automatic tampering detection. We present experimental results on benchmark and real-world data, and analyze the results. We observe that the proposed method yields promising results compared to the state of the art, especially with respect to the algorithm’s ability to generalize to unknown data taken from the real world. We conclude with the research directions that our work in InVID has opened for the future

Impact of SARS-CoV-2 Pandemic on Patients with Primary Immunodeficiency

Although it is estimated that COVID-19 life-threatening conditions may be diagnosed in less than 1:1000 infected individuals below the age of 50, but the real impact of this pandemic on pediatric patients with different types of primary immunodeficiency (PID) is not elucidated. The current prospective study on a national registry of PID patients showed that with only 1.23 folds higher incidence of infections, these patients present a 10-folds higher mortality rate compared to population mainly in patients with combined immunodeficiency and immune dysregulation. Therefore, further management modalities against COVID-19 should be considered to improve the survival rate in these two PID entities using hematopoietic stem cell transplantation and immunomodulatory agents. © 2020, The Author(s)

Solvent-free synthesis of bis(2,2′:6′,2′′-terpyridin-4′-yl)amine and its metal complexes

The key compound bis(2,2′:6′,2′′-terpyridin-4′-yl)amine was prepared in one step starting from 4′-amino-2,2′:6′,2′′-terpyridine and 4′-bromo-2,2′:6′,2′′-terpyridine in quantitative yield. In addition, we have established an easy and efficient route for the synthesis of the bromoterpyridine compound. Using the novel ligand, two ruthenium complexes were also prepared

Azido- and ethynyl-substituted 2,2’:6,2’’-terpyridines as suitable substrates for click reactions

The click reaction of azido- and ethynyl-functionalized terpyridines has been exploited to obtain a series of 1H-1,2,3-triazole-substituted terpyridines. This protocol was extended towards the synthesis of terpyridine-based macroligands via end group modification of ethynyl-functionalized polymers. Finally, the combination of two orthogonal terpyridines within one click reaction highlights the potential of this approach with respect to the preparation of new building blocks for supramolecular assemblies and functional materials