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Background/Objectives: Recent advances in stroke genetics have substantially enhanced our understanding of the complex genetic architecture underlying cerebral infarction and other stroke subtypes. As knowledge in this field expands, healthcare providers must remain informed about these latest developments. This review aims to provide a comprehensive overview of recent advances in stroke genetics, with a focus on cerebral infarction, and discuss their potential impact on patient care and future research directions. Methods: We reviewed recent literature about advances in stroke genetics, focusing on cerebral infarction, and discussed their potential impact on patient care and future research directions. Key developments include the identification of monogenic stroke syndromes, such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, and cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy caused by mutations in the NOTCH3 and HTRA1 genes, respectively. In addition, the role of RNF213 in moyamoya disease and other cerebrovascular disorders, particularly in East Asian populations, has been elucidated. The development of polygenic risk scores for assessing genetic predisposition to stroke has demonstrated the potential to improve risk prediction beyond traditional factors. Genetic studies have also elucidated the distinct genetic architecture of stroke subtypes, including large artery atherosclerosis, small vessel disease, and cardioembolic stroke. Furthermore, the investigation of epigenetic modifications influencing stroke risk and its outcomes has revealed new research avenues, while advancements in pharmacogenomics highlight the potential for personalized stroke treatment based on individual genetic profiles. Conclusions: These genetic discoveries have important clinical implications, including improved risk stratification, targeted prevention strategies, and the development of novel therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background and Aims: Short courses of intravenous (iv) methylprednisolone (MP) can cause drug induced liver injury (DILI). The aim of this study was to assess the clinical features and HLA associations of MP-related DILI enrolled in the US DILI Network (DILIN)., Methods: DILIN cases with MP as a suspected drug were reviewed. DILIN causality scoring was assigned on a 5-point scale (definite, highly likely, probable, possible, unlikely). All cases with MP causality scores of definite, highly likely or probable were analysed. HLA data from direct sequencing were analysed., Results: Eleven cases of definite, highly likely, or probable MP DILI were identified. The median age was 48 years; 73% were female; median latency to onset was 30 days; 55% were jaundiced; and all had hepatocellular injury with one patient requiring transplantation. Nine of the 11 cases were in patients with multiple sclerosis (MS). Liver biopsies in 7 cases revealed mild acute hepatitis with/without cholestasis. HLA data demonstrated that HLA-DRB1*15:01, the primary HLA class II allele associated with MS was over-represented. HLA-DQB1*06:02-HLA-DQA1*01:02 which is haplotypic with the HLA-DRB1*15 haplotype was more common in the MP DILI cases compared to other DILI controls (p = 0.03) and to DILI controls exposed to MP (p = 0.04)., Conclusion: MP DILI is characterised by hepatocellular injury, short latency and generally rapid recovery. There was no independent HLA haplotype associated with MP DILI., (© 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

HLA-B*27 confers a strong risk of developing spondyloarthritis (SpA), which includes axial SpA with or without peripheral arthritis, enthesitis, acute anterior uveitis and gastrointestinal inflammation. Although no definitive mechanism has been established to explain the role of this HLA class I protein in the pathogenesis of SpA, three main hypotheses have emerged. First is the idea that self-peptides displayed by HLA-B27 resemble microorganism-derived peptides, leading to the expansion of autoreactive CD8 + T cells that trigger disease. The second and third hypotheses focus on aberrant properties of HLA-B27, including its tendency to form cell-surface dimers that can activate innate killer immunoglobulin-like receptors on CD4 + T helper 17 cells, triggering the production of pathogenic cytokines. HLA-B27 also misfolds in the endoplasmic reticulum, which can activate the unfolded protein response, increasing IL-23 expression and thereby promoting the production of type 17 cytokines. HLA-B27 misfolding in mesenchymal stem cells has also been linked to enhanced bone formation by mesenchymal stem cell-derived osteoblasts, which could contribute to structural damage in axial SpA. In this Review we summarize prevailing ideas about the role of HLA-B27 in SpA, discuss the latest developments as well as the gaps in current knowledge, and provide recommendations for future research to address these unmet needs., Competing Interests: Competing interests: R.A.C. has received funding from Novartis, L.C. has received funding from Novartis, P.B. has received institutional research funding from Merck, Benevolent AI, GSK, Regeneron and Novartis., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Purpose of Review: Axial spondyloarthritis (axSpA) is a rather prevalent chronic inflammatory rheumatic disease that affects already relatively young patients. It has been known better since the end of the nineteenth century but quite a lot has been learned since the early 60ies when the first classification (diagnostic) criteria for ankylosing spondylitis (AS) were agreed on. I have been part of many developments in the last 30 years, and I'm happy to have been able to contribute to the scientific progress in terms of diagnosis, imaging, pathophysiology and therapy. When I was asked to write a manuscript about the SpA concept I felt honored. Thus, the purpose of this extensive review was, on the one hand, to describe the history of AS and axSpA, and on the other hand, to reason about the concept and the gestalt of axSpA, and finally to deliver some ideas what future researchers could possibly do to further study the disease., Recent Findings: The last 3 decades were full of innovations for both, classification and treatment of axSpA which also helped us to learn about the pathophysiology. Thus, TNFa, IL-17, IL-23 and Janus kinase are established targets to reduce inflammation. IL-17 and IL-23 are very special in that regard because they both work for psoriasis but only anti-IL-17 agents which don't work in IBD are approved for axSpA, while IL 23 inhibitors are approved for both, psoriasis and IBD, but they don't work in axSpA. New imaging techniques such as low dose CT and synthetic MRI are likely to improve the detection of both active and structural lesions of axSpA. This manuscript tries to describe the most important findings about axSpA. The main aim of research remains to discover the pathophysiology and to further improve treatment options in order to reduce and abolish inflammation and prevent new bone formation to increase the quality of life of our patients. The differences between male and female disease and the role of the immune system in axSpA are now the main challenges, and the role of special T-cell receptors seem to deserve special interest., Competing Interests: Declarations. Human and Animal Rights and Informed Consent: This article does not contain any studies with human or animal subjects performed by the author. Conflict of Interest: The author declares no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Roman writers found the relative empowerment of Celtic women remarkable 1 . In southern Britain, the Late Iron Age Durotriges tribe often buried women with substantial grave goods 2 . Here we analyse 57 ancient genomes from Durotrigian burial sites and find an extended kin group centred around a single maternal lineage, with unrelated (presumably inward migrating) burials being predominantly male. Such a matrilocal pattern is undescribed in European prehistory, but when we compare mitochondrial haplotype variation among European archaeological sites spanning six millennia, British Iron Age cemeteries stand out as having marked reductions in diversity driven by the presence of dominant matrilines. Patterns of haplotype sharing reveal that British Iron Age populations form fine-grained geographical clusters with southern links extending across the channel to the continent. Indeed, whereas most of Britain shows majority genomic continuity from the Early Bronze Age to the Iron Age, this is markedly reduced in a southern coastal core region with persistent cross-channel cultural exchange 3 . This southern core has evidence of population influx in the Middle Bronze Age but also during the Iron Age. This is asynchronous with the rest of the island and points towards a staged, geographically granular absorption of continental influence, possibly including the acquisition of Celtic languages., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

After a long-distance migration, Avars with Eastern Asian ancestry arrived in Eastern Central Europe in 567 to 568 CE and encountered groups with very different European ancestry 1,2 . We used ancient genome-wide data of 722 individuals and fine-grained interdisciplinary analysis of large seventh- to eighth-century CE neighbouring cemeteries south of Vienna (Austria) to address the centuries-long impact of this encounter 1,2 . We found that even 200 years after immigration, the ancestry at one site (Leobersdorf) remained dominantly East Asian-like, whereas the other site (Mödling) shows local, European-like ancestry. These two nearby sites show little biological relatedness, despite sharing a distinctive late-Avar culture 3,4 . We reconstructed six-generation pedigrees at both sites including up to 450 closely related individuals, allowing per-generation demographic profiling of the communities. Despite different ancestry, these pedigrees together with large networks of distant relatedness show absence of consanguinity, patrilineal pattern with female exogamy, multiple reproductive partnerships (for example, levirate) and direct correlation of biological connectivity with archaeological markers of social status. The generation-long genetic barrier was maintained by systematically choosing partners with similar ancestry from other sites in the Avar realm. Leobersdorf had more biological connections with the Avar heartlands than with Mödling, which is instead linked to another site from the Vienna Basin with European-like ancestry. Mobility between sites was mostly due to female exogamy pointing to different marriage networks as the main driver of the maintenance of the genetic barrier., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)