The feasibility of wireless capsule endoscopy in detecting small intestinal pathology in children under the age of 8 years: a multicentre European study.

Objective: To systematically evaluate the feasibility and methodology to carry out wireless capsule endoscopy (WCE) in children <8 years to define small intestinal pathology. Design: Prospective European multicentre study with negative prior investigation. Patients and interventions: 83 children aged 1.5–7.9 years were recruited. Initially, all were offered “swallowing” (Group 1) for capsule introduction. If this failed endoscopic placement (Group 2) was used and the Roth net, Advance or custom-made introducers were compared. Outcome measures: Primary endpoint: to determine pathology; secondary endpoint: comparison of capsule introduction methods. Results: Capsule introduction: 20 (24%) children aged 4.0–7.9 years (mean, 6.9 years; 14 male) comprising Group 1 were older (p<0.025) than 63 (76%) aged 1.5–7.9 years (mean, 5.25 years; 30 male) forming Group 2. Complications: Roth net mucosal trauma in 50%; no others occurred. The available recording apparatus was inappropriate for those <3 years. Indications: gastrointestinal bleeding: n = 30 (16 positive findings: four ulcerative jejunitis, four polyps, two angiodysplasia, two blue rubber blebs, two Meckel’s diverticula, one anastomotic ulcer, one reduplication); suspected Crohn’s disease: n = 20 (11 had Crohn’s disease); abdominal pain: n = 12 (six positive findings: three Crohn’s disease, two lymphonodular hyperplasia, one blue rubber bleb); protein loss: n = 9 (four lymphangectasia); malabsorption: n = 12 (seven positive findings: six enteropathy, one ascaris). No abnormalities overall: 45%. Conclusion: WCE is feasible and safe down to the age of 1.5 years. 20 children >4 years swallowed the capsule. The Advance introducer proved superior for endoscopic placement. The pathologies encountered showed age specificity and, unlike in adolescents, obscure gastrointestinal bleeding was the commonest indication

Neural-Symbolic Argumentation Mining: An Argument in Favor of Deep Learning and Reasoning

Deep learning is bringing remarkable contributions to the field of argumentation mining, but the existing approaches still need to fill the gap toward performing advanced reasoning tasks. In this position paper, we posit that neural-symbolic and statistical relational learning could play a crucial role in the integration of symbolic and sub-symbolic methods to achieve this goal

The Multifaceted Origin of Taurine Cattle Reflected by the Mitochondrial Genome

A Neolithic domestication of taurine cattle in the Fertile Crescent from local aurochsen (Bos primigenius) is generally accepted, but a genetic contribution from European aurochsen has been proposed. Here we performed a survey of a large number of taurine cattle mitochondrial DNA (mtDNA) control regions from numerous European breeds confirming the overall clustering within haplogroups (T1, T2 and T3) of Near Eastern ancestry, but also identifying eight mtDNAs (1.3%) that did not fit in haplogroup T. Sequencing of the entire mitochondrial genome showed that four mtDNAs formed a novel branch (haplogroup R) which, after the deep bifurcation that gave rise to the taurine and zebuine lineages, constitutes the earliest known split in the mtDNA phylogeny of B. primigenius. The remaining four mtDNAs were members of the recently discovered haplogroup Q. Phylogeographic data indicate that R mtDNAs were derived from female European aurochsen, possibly in the Italian Peninsula, and sporadically included in domestic herds. In contrast, the available data suggest that Q mtDNAs and T subclades were involved in the same Neolithic event of domestication in the Near East. Thus, the existence of novel (and rare) taurine haplogroups highlights a multifaceted genetic legacy from distinct B. primigenius populations. Taking into account that the maternally transmitted mtDNA tends to underestimate the extent of gene flow from European aurochsen, the detection of the R mtDNAs in autochthonous breeds, some of which are endangered, identifies an unexpected reservoir of genetic variation that should be carefully preserved

Projecting Ancient Ancestry in Modern-Day Arabians and Iranians: A Key Role of the Past Exposed Arabo-Persian Gulf on Human Migrations

The Arabian Peninsula is strategic for investigations centered on the early structuring of modern humans in the wake of the out-of-Africa migration. Despite its poor climatic conditions for the recovery of ancient human DNA evidence, the availability of both genomic data from neighboring ancient specimens and informative statistical tools allow modeling the ancestry of local modern populations. We applied this approach to a data set of 741,000 variants screened in 291 Arabians and 78 Iranians, and obtained insightful evidence. The west-east axis was a strong forcer of population structure in the Peninsula, and, more importantly, there were clear continuums throughout time linking western Arabia with the Levant, and eastern Arabia with Iran and the Caucasus. Eastern Arabians also displayed the highest levels of the basal Eurasian lineage of all tested modern-day populations, a signal that was maintained even after correcting for a possible bias due to a recent sub-Saharan African input in their genomes. Not surprisingly, eastern Arabians were also the ones with highest similarity with Iberomaurusians, who were, so far, the best proxy for the basal Eurasians amongst the known ancient specimens. The basal Eurasian lineage is the signature of ancient non-Africans who diverged from the common European-eastern Asian pool before 50,000 years ago, prior to the later interbred with Neanderthals. Our results appear to indicate that the exposed basin of the Arabo-Persian Gulf was the possible home of basal Eurasians, a scenario to be further investigated by searching ancient Arabian human specimens.This work was financed by FEDER-Fundo Europeu de Desenvolvimento Regional funds through COMPETE 2020-Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020, by Portuguese funds through FCT-Fundação para a Ciência e a Tecnologia, Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Biomedical anthropological study in Arabian Peninsula based on high-throughput genomics” (POCI-01-0145-FEDER-016609), the Italian Ministry of Education, University and Research project Dipartimenti di Eccellenza Program (2018–2022)—Department of Biology and Biotechnology “L. Spallanzani,” University of Pavia (to A.T.). V.F. has a postdoc grant through FCT (SFRH/BPD/114927/2016). i3S is financed by FEDER-COMPETE 2020, Portugal 2020 and by Portuguese funds through FCT in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274). Authors would like to thank Dr Francesco Bertolini for facilitating the research of A.R. in the last stage of the article preparation

Mitochondrial DNA signals of late glacial recolonization of Europe from near Eastern refugia

Human populations, along with those of many other species, are thought to have contracted into a number of refuge areas at the height of the last Ice Age. European populations are believed to be, to a large extent, the descendants of the inhabitants of these refugia, and some extant mtDNA lineages can be traced to refugia in Franco-Cantabria (haplogroups H1, H3, V, and U5b1), the Italian Peninsula (U5b3), and the East European Plain (U4 and U5a). Parts of the Near East, such as the Levant, were also continuously inhabited throughout the Last Glacial Maximum, but unlike western and eastern Europe, no archaeological or genetic evidence for Late Glacial expansions into Europe from the Near East has hitherto been discovered. Here we report, on the basis of an enlarged whole-genome mitochondrial database, that a substantial, perhaps predominant, signal from mitochondrial haplogroups J and T, previously thought to have spread primarily from the Near East into Europe with the Neolithic population, may in fact reflect dispersals during the Late Glacial period, ?19–12 thousand years (ka) ago.<br/

Arrival of Paleo-Indians to the Southern Cone of South America: New Clues from Mitogenomes

With analyses of entire mitogenomes, studies of Native American mitochondrial DNA (mtDNA) variation have entered the final phase of phylogenetic refinement: the dissection of the founding haplogroups into clades that arose in America during and after human arrival and spread. Ages and geographic distributions of these clades could provide novel clues on the colonization processes of the different regions of the double continent. As for the Southern Cone of South America, this approach has recently allowed the identification of two local clades (D1g and D1j) whose age estimates agree with the dating of the earliest archaeological sites in South America, indicating that Paleo-Indians might have reached that region from Beringia in less than 2000 years. In this study, we sequenced 46 mitogenomes belonging to two additional clades, termed B2i2 (former B2l) and C1b13, which were recently identified on the basis of mtDNA control-region data and whose geographical distributions appear to be restricted to Chile and Argentina. We confirm that their mutational motifs most likely arose in the Southern Cone region. However, the age estimate for B2i2 and C1b13 (11–13,000 years) appears to be younger than those of other local clades. The difference could reflect the different evolutionary origins of the distinct South American-specific sub-haplogroups, with some being already present, at different times and locations, at the very front of the expansion wave in South America, and others originating later in situ, when the tribalization process had already begun. A delayed origin of a few thousand years in one of the locally derived populations, possibly in the central part of Chile, would have limited the geographical and ethnic diffusion of B2i2 and explain the present-day occurrence that appears to be mainly confined to the Tehuelche and Araucanian-speaking grou

The Phylogeny of the Four Pan-American MtDNA Haplogroups: Implications for Evolutionary and Disease Studies

Only a limited number of complete mitochondrial genome sequences belonging to Native American haplogroups were available until recently, which left America as the continent with the least amount of information about sequence variation of entire mitochondrial DNAs. In this study, a comprehensive overview of all available complete mitochondrial DNA (mtDNA) genomes of the four pan-American haplogroups A2, B2, C1, and D1 is provided by revising the information scattered throughout GenBank and the literature, and adding 14 novel mtDNA sequences. The phylogenies of haplogroups A2, B2, C1, and D1 reveal a large number of sub-haplogroups but suggest that the ancestral Beringian population(s) contributed only six (successful) founder haplotypes to these haplogroups. The derived clades are overall starlike with coalescence times ranging from 18,000 to 21,000 years (with one exception) using the conventional calibration. The average of about 19,000 years somewhat contrasts with the corresponding lower age of about 13,500 years that was recently proposed by employing a different calibration and estimation approach. Our estimate indicates a human entry and spread of the pan-American haplogroups into the Americas right after the peak of the Last Glacial Maximum and comfortably agrees with the undisputed ages of the earliest Paleoindians in South America. In addition, the phylogenetic approach also indicates that the pathogenic status proposed for various mtDNA mutations, which actually define branches of Native American haplogroups, was based on insufficient grounds

Mutation Rate Switch inside Eurasian Mitochondrial Haplogroups: Impact of Selection and Consequences for Dating Settlement in Europe

R-lineage mitochondrial DNA represents over 90% of the European population and is significantly present all around the planet (North Africa, Asia, Oceania, and America). This lineage played a major role in migration “out of Africa” and colonization in Europe. In order to determine an accurate dating of the R lineage and its sublineages, we analyzed 1173 individuals and complete mtDNA sequences from Mitomap. This analysis revealed a new coalescence age for R at 54.500 years, as well as several limitations of standard dating methods, likely to lead to false interpretations. These findings highlight the association of a striking under-accumulation of synonymous mutations, an over-accumulation of non-synonymous mutations, and the phenotypic effect on haplogroup J. Consequently, haplogroup J is apparently not a Neolithic group but an older haplogroup (Paleolithic) that was subjected to an underestimated selective force. These findings also indicated an under-accumulation of synonymous and non-synonymous mutations localized on coding and non-coding (HVS1) sequences for haplogroup R0, which contains the major haplogroups H and V. These new dates are likely to impact the present colonization model for Europe and confirm the late glacial resettlement scenario

Analysis of the human Y-chromosome haplogroup Q characterizes ancient population movements in Eurasia and the Americas

Background: Recent genome studies of modern and ancient samples have proposed that Native Americans derive from a subset of the Eurasian gene pool carried to America by an ancestral Beringian population, from which two well-differentiated components originated and subsequently mixed in different proportion during their spread in the Americas. To assess the timing, places of origin and extent of admixture between these components, we performed an analysis of the Y-chromosome haplogroup Q, which is the only Pan-American haplogroup and accounts for virtually all Native American Y chromosomes in Mesoamerica and South America. Results: Our analyses of 1.5 Mb of 152 Y chromosomes, 34 re-sequenced in this work, support a "coastal and inland routes scenario" for the first entrance of modern humans in North America. We show a major phase of male population growth in the Americas after 15 thousand years ago (kya), followed by a period of constant population size from 8 to 3 kya, after which a secondary sign of growth was registered. The estimated dates of the first expansion in Mesoamerica and the Isthmo-Colombian Area, mainly revealed by haplogroup Q-Z780, suggest an entrance in South America prior to 15 kya. During the global constant population size phase, local South American hints of growth were registered by different Q-M848 sub-clades. These expansion events, which started during the Holocene with the improvement of climatic conditions, can be ascribed to multiple cultural changes rather than a steady population growth and a single cohesive culture diffusion as it occurred in Europe. Conclusions: We established and dated a detailed haplogroup Q phylogeny that provides new insights into the geographic distribution of its Eurasian and American branches in modern and ancient samples