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Introduction Methods Results Conclusion Activation‐induced cytidine deaminase (AID) deficiency is a rare autosomal recessive inborn error of immunity (IEI) characterized by increased susceptibility to infections, autoimmunity, and/or autoinflammation. AID plays an important role in immunoglobulin class switching and somatic hypermutation. AID deficiency patients have very low or absent levels of IgG, IgA, and IgE, while IgM level is elevated. The disease is designated as type 2 hyperimmunoglobulin M syndrome (HIGM‐2). To date, around 130 patients with HIGM‐2 have been reported, none from Egypt.Four patients from three different consanguineous families with elevated serum IgM and low IgG and IgA were included in the study. After the exclusion of CD40 and/or CD40L deficiency by flow cytometry, patients’ samples were tested by a panel covering 452 genes (four bases PID‐Pro) on the Illumina Miseq platform.All patients suffered repeated infections since childhood. Patients 1–3 had inflammatory bowel disease‐like (IBD‐like) symptoms, while patient 4 did not have autoimmune manifestations. Patient 1 is the first HIGM‐2 patient to be reported to have renal amyloidosis as part of the autoinflammation. Patients 1–3 had the same pathogenic variant (NM_020661.4 (AID):c.406del, p.Ile136Ter), while patient 4 had another pathogenic variant (NM_020661.4 (AID):c.374G > A, p.Gly125Glu). The variant p.Ile136Ter was not reported before in any of the documented HIGM‐2 patients.HIGM‐2 is a rare IEI that can be overlooked; hence, patients’ diagnosis is delayed. Autoimmune and autoinflammatory manifestations develop later in the disease course leading to significant morbidities. The diagnosis can be suspected after exclusion of CD40/CD40L deficiencies by flow cytometry, and the diagnosis can be confirmed by genetic testing. [ABSTRACT FROM AUTHOR]

The Nigerian state is expected to perform functions critical to the protection of citizens against disasters and harmful emergency situations through effective management of humanitarian aid. However, the reality in Nigeria shows that the government is only interested in the relocation of internally displaced people (IDP) rather than their daily survival in humanitarian camps. In addressing this problem, this article examined the indicators, reasons, and implications of the unsustainability of humanitarian aid. It is believed that research in this direction would provide an understanding of a better approach to improving the sustainability of humanitarian aid. Drawing on the state fragility theory and mixed qualitative methods involving observations, interviews, and document analysis, the findings identified a lack of capacity to control violence causing displacement, weak institutional support, political will, and capacity to finance humanitarian aid as reasons why humanitarian aid is unsustainable in IDP camps in Nigeria. It also identified the depletion of host communities’ resources, untimely deaths, harmful coping strategies, and an increased rate of out-of-school children, among others, as the implications of unsustainable humanitarian aid. The findings suggest means through which the Nigerian government can sustain humanitarian aid in IDP camps in Nigeria. [ABSTRACT FROM AUTHOR]

Antibody diversification is essential for an effective immune response, with somatic hypermutation (SHM) serving as a key molecular process in this adaptation. Activation-induced cytidine deaminase (AID) initiates SHM by inducing DNA lesions, which are ultimately resolved into point mutations, as well as small insertions and deletions (indels). These mutational outcomes contribute to antibody affinity maturation. The mechanisms responsible for generating point mutations and indels involve the base excision repair (BER) and mismatch repair (MMR) pathways, which are well coordinated to maintain genomic integrity while allowing for beneficial mutations to occur. In this regard, translesion synthesis (TLS) polymerases contribute to the diversity of mutational outcomes in antibody genes by enabling the bypass of DNA lesions. This review summarizes our current understanding of the distinct molecular mechanisms that generate point mutations and indels during SHM. Understanding these mechanisms is critical for elucidating the development of broadly neutralizing antibodies (bnAbs) and autoantibodies, and has implications for vaccine design and therapeutics. [ABSTRACT FROM AUTHOR]

This article explores the European Union's (EU) aid policy process and, more precisely, the factors through which member states (MS) shape the formulation of development cooperation policy at the EU level. Following literature on EU policy processes, we identify the several influence factors available for MS to advance their priorities in the context of defining EU aid policy and legislation. Thematically, these refer to MS' national institutional frameworks, their strategic vision and coordination, their human resources, the interactions among representatives and actors in Brussels and structural factors. The relevance and functioning of these factors when MS shape EU development cooperation policy are then explored through semi-structured interviews, showing that the exertion of power on the part of MS is not limited to their economic size or financial contributions and that influence is the result of the combination of a wide array of factors in the domains of coalitions, power resources, networks, institutions, and critical junctures. [ABSTRACT FROM AUTHOR]

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AbstractNGOs are perceived as organisations that are always seeking funding. However, there are many instances where donations are refused by NGOs. This counter-intuitive decision, given the often grave humanitarian needs, is not well documented beyond brief references or individual cases. Refusal is an expression of values and principles, important for actors that are often portrayed as having little to no agency or power in relation to donors. We developed a database of 32 examples of funding refusals by NGOs detailing the reasons for refusal. To classify and compare the refusals, we developed a preliminary typology of NGO motivations for donor refusal, which contains four types (independence, impartiality, neutrality, and humanity) that align with humanitarian principles. Each category and type are defined and examples of each are provided. Given the focal nature of NGOs in development activity, the lack of attention to funding refusal is notable. We address this lacuna by creating a database and developing a preliminary typology to provide a foundation for future research. This study contributes a novel typology to an under-studied topic. In so doing, this paper provides a foundation for studies of refusal to follow. [ABSTRACT FROM AUTHOR]

Drawing on the human ecology framework, which describes social structure as dynamic and social action as environmentally contingent, this article examines behavior and attitudes around accepting help after disaster. Through two years of longitudinal in-depth interviews with 59 households in one community whose homes flooded during Hurricane Harvey, this study describes perceived shifts in the help provided by local organizations, institutions, and the social networks of community members—or what we call the local ecology of aid. While flood victims experienced an immense, and seemingly universal, outpouring of support in the immediate aftermath of the storm, in the ensuing months they reported a sharp decrease in this interpersonal support. In the absence of a local ecology of aid marked by the universal provision of aid, concerns about stigmatization began to inform decisions about accepting help. Our findings have implications for ecological theorizing, for understanding stigma and help-seeking or accepting help, as well as for fostering community resilience—a growing concern given the expanding scope and intensity of climate-related disasters. [ABSTRACT FROM AUTHOR]

One of the primary reasons behind the pathogenesis of T cell acute lymphoblastic leukemia (T-ALL) is the deregulation of the transcription factor BCL11B. The exon 4 of BCL11B harbors several driver mutations, which abolishes its DNA-binding ability. The high frequency of C > T or G > A conversion in close vicinity of AID (Activation-induced cytidine deaminase)-hotspot motifs in the deregulated gene prompted us to investigate the role of AID in BCL11B mutagenesis. Our results reveal that AID is expressed in T-ALL patient-derived cells, binds to BCL11B fragile region (FR) in exon 4 of T cells in vivo, and generates a signature mutation pattern in this region. The mutation frequency in BCL11B FR could be modulated upon overexpression of the AID gene in the knockout background, further suggesting the involvement of AID in BCL11B mutagenesis. Importantly, various lines of experimentation reveal that BCL11B FR could fold into parallel G-quadruplex, triplex, and hairpin structures, which could act as a replication/transcription block, causing mutagenesis. Thus, our results suggest that AID binds to BCL11B exon 4 due to non-B DNA formation, causing U:G mismatches or replication blocks, which, when repaired erroneously, generates deleterious mutations, resulting in loss of functionality of BCL11B, and thus becomes the cause of T-ALL. [ABSTRACT FROM AUTHOR]

South Korea’s national healthcare system after liberation often described as transformation from ‘sanitation’ to ‘public health’. The U.S. military government introduced public health nursing as the primary vehicle for communicating the newly introduced concept of public health to the Korean public. This meant that nursing, which had been in a subordinate position within the healthcare system during the Japanese occupation, had to be repositioned within the healthcare system as an independent and leading professional agent of healthcare. At the same time creating positions for public health nurses within the newly envisioned health center system, and convincing the public that nurses were the primary agents of public health activities. Yet, in resource limited setting, the role of public health nurses was significantly scaled back. Initial plans for institutionalized, community-wide health care through home visits shifted to addressing the challenges facing Korean society, including maternal and child health and infectious disease prevention. Ironically, the expansion of health centers during late 1950s diminished the position of public health nurses within local government health systems, who were gradually replaced by male administrative staff. The role of public health nurses was greatly curtailed in the 1960s, but they laid the groundwork for later community nursing and health care efforts. At the same time, public health nurses were assigned with new role of ‘visiting’ local health centers for observation, education, and management. Public health nursing allows to look beyond the ideological and institutional dimensions to examine how new concepts and practices of “public health” were actually transmitted to communities in post-liberation Korea.