Growth trajectories of the human fetal brain in healthy and complicated pregnancies and associations with neurodevelopmental outcome in the early life course

Background There is a need for non-invasive prenatal markers of the brain to assess fetuses at risk for poor postnatal neurodevelopmental outcome. Periconceptional maternal conditions and pregnancy complications impact prenatal brain development. Aims To investigate associations between growth trajectories of fetal brain structures and neurodevelopmental outcome in children in the early life course. Study design Periconceptional prospective observational cohort. Subjects Singleton pregnancies were included in the Rotterdam periconception cohort. Two- and three-dimensional ultrasound scans at 22, 26 and 32 weeks gestational age were analysed. Outcome measures Head circumference (HC), cerebellum, corpus callosum (CC), Sylvian fissure, insula and parieto-occipital fissure (POF) were measured. Neurodevelopment was evaluated using the Age-and-Stages-questionnaire-3 (ASQ-3) and the Child-Behaviour-Checklist (CBCL) at 2 years of age. Linear mixed models, used to estimate the prenatal brain growth trajectories, and linear regression models, used to evaluate the associations between prenatal brain structures and neurodevelopmental outcomes, were applied in the total study population, and in subgroups: fetal growth restriction (FGR), preterm birth (PTB), fetal congenital heart

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

A novel family illustrating the mild phenotypic spectrum of TUBB2B variants

TUBB2B codes for one of the isotypes of β-tubulin and dominant negative variants in this gene result in distinctive malformations of cortical development (MCD), including dysgyria, dysmorphic basal ganglia and cerebellar anomalies. We present a novel family with a heterozygous missense variant in TUBB2B and an unusually mild phenotype. First, at 21 [Formula presented] weeks of gestation ultrasonography revealed a fetus with a relatively small head, enlarged lateral ventricles, borderline hypoplastic cerebellum and a thin corpus callosum. The couple opted for pregnancy termination. Exome sequencing on fetal material afterwards identified a heterozygous maternally inherited variant in TUBB2B (NM_178012.4 (TUBB2B):c.530A &gt; T, p.(Asp177Val)), not present in GnomAD and predicted as damaging. The healthy mother had only a language delay in childhood. This inherited TUBB2B variant prompted re-evaluation of the older son of the couple, who presented with a mild delay in motor skills and speech. His MRI revealed mildly enlarged lateral ventricles, a thin corpus callosum, mild cortical dysgyria, and dysmorphic vermis and basal ganglia, a pattern typical of tubulinopathies. This son finally showed the same TUBB2B variant, supporting pathogenicity of the TUBB2B variant. These observations illustrate the wide phenotypic heterogeneity of tubulinopathies, including reduced penetrance and mild expressivity, that require careful evaluation in pre- and postnatal counseling.</p

Tectonic Processes Along the Chile Convergent Margin

The Chile subduction zone, spanning more than 3500 km, provides a unique setting for studying, along a single plate boundary, the factors that govern tectonic processes at convergent margins. At large scale, the Chile trench is segmented by the subduction of the Chile Rise, an active spreading center, and by the Juan Fernández hot spot ridge. In addition, the extreme climatic change from the Atacama Desert in the north to the glacially influenced southern latitudes produces a dramatic variability in the volume of sediment supplied to the trench. The distribution of sediment along the trench is further influenced by the high relief gradients of the segmented oceanic lithosphere. We interpret new and reprocessed multichannel seismic reflection profiles, and multibeam bathymetric data, to study the variability in tectonic processes along the entire convergent margin. In central and south Chile, where the trench contains thick turbidite infill, accretionary prisms, some 50–60 km wide, have developed. These prisms, however, are ephemeral and can be rapidly removed by high-relief, morphological features on the incoming oceanic plate. Where topographic barriers inhibit the transport of turbidites along the trench, sediment infill abruptly decreases to less than 1 km thick and is confined to a narrow zone at the trench axis. There, all sediment is subducted; the margin is extending by normal faulting and collapsing due to basal tectonic erosion. The transition from accretion to tectonic erosion occurs over short distances (a few tens of km) along the trench. In the turbidite-starved northern Chile trench, ~1 km of slope debris reaches the trench and is subsequently subducted. There, tectonic erosion is causing pronounced steepening of the margin, associated pervasive extension across the slope and into the emerged coastal area, and consequent collapse of the overriding plate. The volume of subducting material varies little along much of the margin. However, the composition of the material varies from slope debris of upper-plate fragments and material removed from the upper plate by basal erosion, to turbidites derived from the Andes