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Western Eurasia witnessed several large-scale human migrations during the Holocene 1-5 . Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes-mainly from the Mesolithic and Neolithic periods-from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a 'great divide' genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 BP, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 BP, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a 'Neolithic steppe' cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations., (© 2024. The Author(s).)

Background: Diagnosis of hypersensitivity (HS) reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) in children is complex. The real prevalence of NSAID HS remains unknown because a drug provocation test (DPT) is not always performed with the culprit NSAID., Objective: To describe and compare the diagnostic workup among different European centers and to find out the real proportion of NSAID HS by performing a DPT with the culprit drug., Methods: We retrospectively collected data from children (0-10 years) and adolescents (10-18 years) with a history of NSAID reactions and who underwent a complete allergy workup including DPTs with the culprit in 6 different pediatric centers: Belgrade, Florence, Geneva, Madrid, Porto, and Rome., Results: A total of 693 children with a history of NSAID reactions were enrolled, and a total of 526 DPTs were performed with the culprit NSAID. The diagnosis of NSAID HS was confirmed in 19.6% (103 of 526) of children by performing a DPT with the culprit drug. The major differences in the allergy workup among the 6 centers concerned the duration of the DPT and the practical use of skin tests for diagnosing NSAID HS. In addition, the use of acetyl salicylic acid to differentiate single reactor or cross-intolerance patients is not common, except in Spain., Conclusion: The value of this study is that although different approaches are used around Europe to diagnose NSAID HS, we found that the percentage of confirmed NSAID HS is less than 20%. This highlights the importance of the DPT in confirming or excluding NSAID HS in the pediatric population., (Copyright © 2019. Published by Elsevier Inc.)

Archaeological evidence indicates that pig domestication had begun by ∼10,500 y before the present (BP) in the Near East, and mitochondrial DNA (mtDNA) suggests that pigs arrived in Europe alongside farmers ∼8,500 y BP. A few thousand years after the introduction of Near Eastern pigs into Europe, however, their characteristic mtDNA signature disappeared and was replaced by haplotypes associated with European wild boars. This turnover could be accounted for by substantial gene flow from local European wild boars, although it is also possible that European wild boars were domesticated independently without any genetic contribution from the Near East. To test these hypotheses, we obtained mtDNA sequences from 2,099 modern and ancient pig samples and 63 nuclear ancient genomes from Near Eastern and European pigs. Our analyses revealed that European domestic pigs dating from 7,100 to 6,000 y BP possessed both Near Eastern and European nuclear ancestry, while later pigs possessed no more than 4% Near Eastern ancestry, indicating that gene flow from European wild boars resulted in a near-complete disappearance of Near East ancestry. In addition, we demonstrate that a variant at a locus encoding black coat color likely originated in the Near East and persisted in European pigs. Altogether, our results indicate that while pigs were not independently domesticated in Europe, the vast majority of human-mediated selection over the past 5,000 y focused on the genomic fraction derived from the European wild boars, and not on the fraction that was selected by early Neolithic farmers over the first 2,500 y of the domestication process., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)