Home-Based Dialysis: A Primer for the Internist.

Home-based dialysis modalities offer both clinical and practical advantages to patients. The use of the home-based modalities, peritoneal dialysis and home hemodialysis, has been increasing over the past decade after a long period of decline. Given the increasing frequency of use of these types of dialysis, it is important for clinicians to be familiar with how these types of dialysis are performed and key clinical aspects of care related to their use in patients with end-stage kidney disease.

Impacts of speciation and extinction measured by an evolutionary decay clock.

The hypothesis that destructive mass extinctions enable creative evolutionary radiations (creative destruction) is central to classic concepts of macroevolution1,2. However, the relative impacts of extinction and radiation on the co-occurrence of species have not been directly quantitatively compared across the Phanerozoic eon. Here we apply machine learning to generate a spatial embedding (multidimensional ordination) of the temporal co-occurrence structure of the Phanerozoic fossil record, covering 1,273,254 occurrences in the Paleobiology Database for 171,231 embedded species. This facilitates the simultaneous comparison of macroevolutionary disruptions, using measures independent of secular diversity trends. Among the 5% most significant periods of disruption, we identify the 'big five' mass extinction events2, seven additional mass extinctions, two combined mass extinction-radiation events and 15 mass radiations. In contrast to narratives that emphasize post-extinction radiations1,3, we find that the proportionally most comparable mass radiations and extinctions (such as the Cambrian explosion and the end-Permian mass extinction) are typically decoupled in time, refuting any direct causal relationship between them. Moreover, in addition to extinctions4, evolutionary radiations themselves cause evolutionary decay (modelled co-occurrence probability and shared fraction of species between times approaching zero), a concept that we describe as destructive creation. A direct test of the time to over-threshold macroevolutionary decay4 (shared fraction of species between two times ≤ 0.1), counted by the decay clock, reveals saw-toothed fluctuations around a Phanerozoic mean of 18.6 million years. As the Quaternary period began at a below-average decay-clock time of 11 million years, modern extinctions further increase life's decay-clock debt.

Where the minor things are: a pan-eukaryotic survey suggests neutral processes may explain much of minor intron evolution.

Spliceosomal introns are gene segments removed from RNA transcripts by ribonucleoprotein machineries called spliceosomes. In some eukaryotes a second 'minor' spliceosome is responsible for processing a tiny minority of introns. Despite its seemingly modest role, minor splicing has persisted for roughly 1.5 billion years of eukaryotic evolution. Identifying minor introns in over 3000 eukaryotic genomes, we report diverse evolutionary histories including surprisingly high numbers in some fungi and green algae, repeated loss, as well as general biases in their positional and genic distributions. We estimate that ancestral minor intron densities were comparable to those of vertebrates, suggesting a trend of long-term stasis. Finally, three findings suggest a major role for neutral processes in minor intron evolution. First, highly similar patterns of minor and major intron evolution contrast with both functionalist and deleterious model predictions. Second, observed functional biases among minor intron-containing genes are largely explained by these genes' greater ages. Third, no association of intron splicing with cell proliferation in a minor intron-rich fungus suggests that regulatory roles are lineage-specific and thus cannot offer a general explanation for minor splicing's persistence. These data constitute the most comprehensive view of minor introns and their evolutionary history to date, and provide a foundation for future studies of these remarkable genetic elements.

Single-cell RNA sequencing of mid-to-late stage spider embryos: new insights into spider development.

BACKGROUND: The common house spider Parasteatoda tepidariorum represents an emerging new model organism of arthropod evolutionary and developmental (EvoDevo) studies. Recent technical advances have resulted in the first single-cell sequencing (SCS) data on this species allowing deeper insights to be gained into its early development, but mid-to-late stage embryos were not included in these pioneering studies. RESULTS: Therefore, we performed SCS on mid-to-late stage embryos of Parasteatoda and characterized resulting cell clusters by means of in-silico analysis (comparison of key markers of each cluster with previously published information on these genes). In-silico prediction of the nature of each cluster was then tested/verified by means of additional in-situ hybridization experiments with additional markers of each cluster. CONCLUSIONS: Our data show that SCS data reliably group cells with similar genetic fingerprints into more or less distinct clusters, and thus allows identification of developing cell types on a broader level, such as the distinction of ectodermal, mesodermal and endodermal cell lineages, as well as the identification of distinct developing tissues such as subtypes of nervous tissue cells, the developing heart, or the ventral sulcus (VS). In comparison with recent other SCS studies on the same species, our data represent later developmental stages, and thus provide insights into different stages of developing cell types and tissues such as differentiating neurons and the VS that are only present at these later stages.

Two Notorious Nodes: a Critical Examination of Relaxed Molecular Clock Age Estimates of the Bilaterian Animals and Placental Mammals.

The popularity of relaxed clock Bayesian inference of clade origin timings has generated several recent publications with focal results considerably older than the fossils of the clades in question. Here we critically examine two such clades: the animals (with focus on the bilaterians); and the mammals (with focus on the placentals). Each example displays a set of characteristic pathologies which, although much commented on, are rarely corrected for. We conclude that in neither case does the molecular clock analysis provide any evidence for an origin of the clade deeper than what is suggested by the fossil record. In addition, both these clades have other features (including, in the case of the placental mammals, proximity to a large mass extinction) that allow us to generate precise expectations of the timings of their origins. Thus, in these instances the fossil record can provide a powerful test of molecular clock methodology, and why it goes astray; and we have every reason to think these problems are general.

New insights into mesoderm and endoderm development, and the nature of the onychophoran blastopore.

BACKGROUND: Early during onychophoran development and prior to the formation of the germ band, a posterior tissue thickening forms the posterior pit. Anterior to this thickening forms a groove, the embryonic slit, that marks the anterior-posterior orientation of the developing embryo. This slit is by some authors considered the blastopore, and thus the origin of the endoderm, while others argue that the posterior pit represents the blastopore. This controversy is of evolutionary significance because if the slit represents the blastopore, then this would support the amphistomy hypothesis that suggests that a slit-like blastopore in the bilaterian ancestor evolved into protostomy and deuterostomy. RESULTS: In this paper, we summarize our current knowledge about endoderm and mesoderm development in onychophorans and provide additional data on early endoderm- and mesoderm-determining marker genes such as Blimp, Mox, and the T-box genes. CONCLUSION: We come to the conclusion that the endoderm of onychophorans forms prior to the development of the embryonic slit, and thus that the slit is not the primary origin of the endoderm. It is thus unlikely that the embryonic slit represents the blastopore. We suggest instead that the posterior pit indeed represents the lips of the blastopore, and that the embryonic slit (and surrounding tissue) represents a morphologically superficial archenteron-like structure. We conclude further that both endoderm and mesoderm development are under control of conserved gene regulatory networks, and that many of the features found in arthropods including the model Drosophila melanogaster are likely derived.

Expression of netrin and its receptors uncoordinated-5 and frazzled in arthropods and onychophorans suggests conserved and diverged functions in neuronal pathfinding and synaptogenesis.

BACKGROUND: Development of the nervous system and the correct connection of nerve cells require coordinated axonal pathfinding through an extracellular matrix. Outgrowing axons exhibit directional growth toward or away from external guidance cues such as Netrin. Guidance cues can be detected by growth cones that are located at the end of growing axons through membrane-bound receptors such as Uncoordianted-5 and Frazzled. Binding of Netrin causes reformation of the cytoskeleton and growth of the axon toward (or away from) the source of Netrin production. RESULTS: Here, we investigate the embryonic mRNA expression patterns of netrin genes and their potential receptors, uncoordinated-5 and frazzled in arthropod species that cover all main branches of Arthropoda, that is, Pancrustacea, Myriapoda, and Chelicerata. We also studied the expression patterns in a closely related outgroup species, the onychophoran Euperipatoides kanangrensis, and provide data on expression profiles of these genes in larval tissues of the fly Drosophila melanogaster including the brain and the imaginal disks. CONCLUSION: Our data reveal conserved and diverged aspects of neuronal guidance in Drosophila with respect to the other investigated species and suggest a conserved function in nervous system patterning of the developing appendages.

Selection and Admixture in a Polytypic Aposematic Frog.

AbstractPhenotypic differentiation within polytypic species is often attributed to selection, particularly when selection might be acting on a trait that serves as a signal for predator avoidance and mate choice. We evaluated this hypothesis by examining phenotypic and genotypic clines between populations of the strawberry poison frog Oophaga pumilio, a polytypic species that exhibits aposematic color pattern variation that is thought to be subject to both natural and sexual selection. Our aim was to assess the extent of admixture and to estimate the strength of selection acting on coloration across a region of Panama where monomorphic populations of distinctly colored frogs are separated by polymorphic populations containing both color variants alongside intermediately colored individuals. We detected sharp clinal transitions across the study region, which is an expected outcome of strong selection, but we also detected evidence of widespread admixture, even at sites far from the phenotypic transition zone. Additionally, genotypic and phenotypic clines were neither concordant nor coincident, and with one exception, selection coefficients estimated from cline attributes were small. These results suggest that strong selection is not required for the maintenance of phenotypic divergence within polytypic species, challenging the long-standing notion that strong selection is implicit in the evolution of warning signals.

Intrinsic Resistance to Colistin in the Genus Hafnia.

A bacterial species is considered to be intrinsically resistant to an antimicrobial when nearly all of the wild-type isolates (i.e., those without acquired resistance) exhibit minimum inhibitory concentration (MIC) values that are sufficiently high such that susceptibility testing is unnecessary, and that the antimicrobial should not be considered for therapy. Accordingly, knowledge of intrinsic resistance influences both the selection of treatment regimens and the approach to susceptibility testing in the clinical laboratory, where unexpected results also facilitate the recognition of microbial identification or susceptibility testing errors. Previously, limited data have suggested that Hafnia spp. may be intrinsically resistant to colistin. We evaluated the in vitro activity of colistin against 119 Hafniaceae that were isolated from human samples: 75 (63%) from routine clinical cultures and 44 (37%) from stool samples of travelers undergoing screening for antimicrobial resistant organisms. Broth microdilution colistin MICs were ≥4 µg/mL for 117 of 119 (98%) isolates. Whole-genome sequencing of 96 of the isolates demonstrated that the colistin-resistant phenotype was not lineage-specific. 2 of the 96 (2%) isolates harbored mobile colistin resistance genes. Compared to whole-genome sequencing, VITEK MS matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and VITEK 2 GN ID failed to consistently distinguish between Hafnia alvei, Hafnia paralvei, and Obesumbacterium proteus. In conclusion, using a reference antimicrobial susceptibility testing method and a genetically diverse collection of isolates, we found Hafnia spp. to be intrinsically resistant to colistin. The recognition of this phenotype will help inform rational approaches by which to perform antimicrobial susceptibility testing and therapy for patients with infections that are caused by Hafnia spp.

Ruthenium(II) Complexes of a Xanthene-Spanned Dicarbene Ligand.

Octahedral ruthenium(II) complexes of a xanthene-di(N-heterocyclic carbene) ancillary ligand (XdC) have been prepared and structurally characterized. Examples catalyze the transfer hydrogenation of ketones {[Ru(CO)I2(C,O,C'-XdC)] (1) and [Ru(CO)(MeCN)2(C,O,C'-XdC)]2+ (22+)} and the selective electrochemical reduction of CO2 to CO {[Ru(N,N'-bpy)(CO)(C,O,C'-XdC)]2+ (32+) at 0.40 V overpotential in MeCN-H2O (1 M)}. The reaction of 1 with KBEt3H afforded isomers of [(C,C'-XdC)Ru(µ-H)(H)]2 dimers, which are stable to reductive elimination of the XdC ligand, thereby suggesting similar (XdC)Rh(coligand)(H)x species may be viable intermediates in catalyses. The electrochemical reduction of CO2 involves a double reduction of 32+ to 3••, which has been characterized by IR-SEC and DFT calculations. The DFT calculations suggest the Ru-Oxanth bond breaks in 3••, opening a metal site for CO2 binding with selectivity over protons enabled by the diffuse nature of the HOMO delocalized over the metal and the bipyridine and carbonyl coligands. The results point to the promise of metal complexes of flexible and hemilabile xanthene-(NHC)2 ancillary ligands in catalysis.

Diffuse retinal dysfunction following immune reconstitution uveitis in patients with prior cytomegalovirus retinitis: a novel observation.

PURPOSE: To report continuing diffuse retinal dysfunction following resolution of immune reconstitution uveitis (IRU) in patients with cytomegalovirus retinitis (CMVR). METHODS: Retrospective case series describing two patients with IRU following CMVR who underwent serial fundus photography and macular optical coherence tomography. One patient had serial electrophysiology. RESULTS: Both patients had CMVR successfully treated with antiviral medication. The affected eyes later developed IRU that resolved with steroids. However, following resolution, chronic retinal damage was evidenced by ellipsoid line loss in one case and gradual optic disc cupping in the other. Electrophysiology in both cases revealed generalized retinal dysfunction worse in the eye with more severe IRU and demonstrated objectively the efficacy of treatment intervention in the patient with serial recordings. CONCLUSIONS: Patients with IRU following CMV retinitis may have continuing diffuse retinal dysfunction despite apparent recovery and normal visual acuity. An aggressive approach to inflammation control may be warranted in such patients.

Melanoma Cells Produce Large Vesicular-Bodies That Cause Rapid Disruption of Brain Endothelial Barrier-Integrity and Disassembly of Junctional Proteins.

It is known that many cells produce extracellular vesicles, and this includes a range of different cancer cell types. Here we demonstrate the profound effects of large vesicular-like bodies produced by melanoma cells on the barrier integrity of human brain endothelial cells. These vesicular-bodies have not been fully characterised but range in size from ~500 nm to >10 µm, are surrounded by membrane and are enzymatically active based on cell-tracker incorporation. Their size is consistent with previously reported large oncosomes and apoptotic bodies. We demonstrate that these melanoma-derived vesicular-bodies rapidly affect brain endothelial barrier integrity, measured using ECIS biosensor technology, where the disruption is evident within ~60 min. This disruption involves acquisition of the vesicles through transcellular uptake into the endothelial cells. We also observed extensive actin-rearrangement, actin removal from the paracellular boundary of the endothelial cells and envelopment of the vesicular-bodies by actin. This was concordant with widespread changes in CD144 localisation, which was consistent with the loss of junctional strength. High-resolution confocal imaging revealed proximity of the melanoma vesicular-bodies juxtaposed to the endothelial nucleus, often containing fragmented DNA themselves, raising speculation over this association and potential delivery of nuclear material into the brain endothelial cells. The disruption of the endothelial cells occurs in a manner that is faster and completely distinct to that of invasion by intact melanoma cells. Given the clinical observation of large vesicles in the circulation of melanoma patients by others, we hypothesize their involvement in weakening or priming the brain vasculature for melanoma invasion.

[Fp(CH4)]+, [η5-CpRu(CO)2(CH4)]+, and [η5-CpOs(CO)2(CH4)]+: A Complete Set of Group 8 Metal-Methane Complexes.

Here, we report the NMR spectroscopic analysis of the group 8 transition metal methane σ-complexes [η5-CpM(CO)2(CH4)][Al(OC(CF3)3)4] (M = Fe, Ru) at -90 °C in the weakly coordinating solvent 1,1,1,3,3,3-hexafluoropropane. The iron(II)-methane complex has a 1H resonance at δ -4.27, a 13C resonance at δ -53.0, and 1JC-H = 126 Hz for the bound methane fragment. The ruthenium(II)-methane complex has a 1H resonance at δ -2.10, a 13C resonance at δ -48.8, and a 1JC-H = 126 Hz for the bound methane fragment. DFT and ab initio calculations support these experimental observations and provide further detail on the structures of the [η5-CpM(CO)2(CH4)]+ (M = Fe, Ru) complexes of the Group 8 metals. Both the iron centered methane complex, [η5-CpFe(CO)2(CH4)][Al(OC(CF3)3)4], and the ruthenium centered methane complex, [η5-CpRu(CO)2(CH4)][Al(OC(CF3)3)4], are significantly less stable than the previously reported osmium-methane complex [η5-CpOs(CO)2(CH4)][Al(OC(CF3)3)4].

Extending Hui-Walter framework to correlated outcomes with application to diagnosis tests of an eye disease among premature infants.

Diagnostic accuracy, a measure of diagnostic tests for correctly identifying patients with or without a target disease, plays an important role in evidence-based medicine. Diagnostic accuracy of a new test ideally should be evaluated by comparing to a gold standard; however, in many medical applications it may be invasive, costly, or even unethical to obtain a gold standard for particular diseases. When the accuracy of a new candidate test under evaluation is assessed by comparison to an imperfect reference test, bias is expected to occur and result in either overestimates or underestimates of its true accuracy. In addition, diagnostic test studies often involve repeated measurements of the same patient, such as the paired eyes or multiple teeth, and generally lead to correlated and clustered data. Using the conventional statistical methods to estimate diagnostic accuracy can be biased by ignoring the within-cluster correlations. Despite numerous statistical approaches have been proposed to tackle this problem, the methodology to deal with correlated and clustered data in the absence of a gold standard is limited. In this article, we propose a method based on the composite likelihood function to derive simple and intuitive closed-form solutions for estimates of diagnostic accuracy, in terms of sensitivity and specificity. Through simulation studies, we illustrate the relative advantages of the proposed method over the existing methods that simply treat an imperfect reference test as a gold standard in correlated and clustered data. Compared with the existing methods, the proposed method can reduce not only substantial bias, but also the computational burden. Moreover, to demonstrate the utility of this approach, we apply the proposed method to the study of National-Eye-Institute-funded Telemedicine Approaches to Evaluating of Acute-Phase Retinopathy of Prematurity (e-ROP), for estimating accuracies of both the ophthalmologist examination and the image evaluation.

Serum biomarkers of neuroinflammation and blood-brain barrier leakage in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is an incurable and rapidly progressive neurological disorder. Biomarkers are critical to understanding disease causation, monitoring disease progression and assessing the efficacy of treatments. However, robust peripheral biomarkers are yet to be identified. Neuroinflammation and breakdown of the blood-brain barrier (BBB) are common to familial and sporadic ALS and may produce a unique biomarker signature in peripheral blood. Using cytometric bead array (n = 15 participants per group (ALS or control)) and proteome profiling (n = 6 participants per group (ALS or control)), we assessed a total of 106 serum cytokines, growth factors, and BBB breakdown markers in the serum of control and ALS participants. Further, primary human brain pericytes, which maintain the BBB, were used as a biosensor of inflammation following pre-treatment with ALS serum. Principal components analysis of all proteome profile data showed no clustering of control or ALS sera, and no individual serum proteins met the threshold for statistical difference between ALS and controls (adjusted P values). However, the 20 most changed proteins between control and ALS sera showed a medium effect size (Cohen's d = 0.67) and cluster analysis of their levels together identified three sample subsets; control-only, mixed control-ALS, and ALS-only. These 20 proteins were predominantly pro-angiogenic and growth factors, including fractalkine, BDNF, EGF, PDGF, Dkk-1, MIF and angiopoietin-2. S100ß, a protein highly concentrated in glial cells and therefore a marker of BBB leakage when found in blood, was unchanged in ALS serum, suggesting that serum protein profiles were reflective of peripheral rather than CNS biofluids. Finally, primary human brain pericytes remained proliferative and their secretome was unchanged by chronic exposure to ALS serum. Our exploratory study suggests that individual serum cytokine levels may not be robust biomarkers in small studies of ALS, but that larger studies using multiplexed analysis of pro-angiogenic and growth factors may identify a peripheral signature of ALS pathogenesis.

Comprehensive database and evolutionary dynamics of U12-type introns.

During nuclear maturation of most eukaryotic pre-messenger RNAs and long non-coding RNAs, introns are removed through the process of RNA splicing. Different classes of introns are excised by the U2-type or the U12-type spliceosomes, large complexes of small nuclear ribonucleoprotein particles and associated proteins. We created intronIC, a program for assigning intron class to all introns in a given genome, and used it on 24 eukaryotic genomes to create the Intron Annotation and Orthology Database (IAOD). We then used the data in the IAOD to revisit several hypotheses concerning the evolution of the two classes of spliceosomal introns, finding support for the class conversion model explaining the low abundance of U12-type introns in modern genomes.

Comprehensive Assessment of Secreted Immuno-Modulatory Cytokines by Serum-Differentiated and Stem-like Glioblastoma Cells Reveals Distinct Differences between Glioblastoma Phenotypes.

Glioblastoma is refractory to therapy and presents a significant oncological challenge. Promising immunotherapies have not shown the promise observed in other aggressive cancers. The reasons for this include the highly immuno-suppressive tumour microenvironment controlled by the glioblastoma cells and heterogeneous phenotype of the glioblastoma cells. Here, we wanted to better understand which glioblastoma phenotypes produced the regulatory cytokines, particularly those that are implicated in shaping the immune microenvironment. In this study, we employed nanoString analysis of the glioblastoma transcriptome, and proteomic analysis (proteome profiler arrays and cytokine profiling) of secreted cytokines by different glioblastoma phenotypes. These phenotypes were cultured to reflect a spectrum of glioblastoma cells present in tumours, by culturing an enhanced stem-like phenotype of glioblastoma cells or a more differentiated phenotype following culture with serum. Extensive secretome profiling reveals that there is considerable heterogeneity in secretion patterns between serum-derived and glioblastoma stem-like cells, as well as between individuals. Generally, however, the serum-derived phenotypes appear to be the primary producers of cytokines associated with immune cell recruitment into the tumour microenvironment. Therefore, these glioblastoma cells have considerable importance in shaping the immune landscape in glioblastoma and represent a valuable therapeutic target that should not be ignored.

Development of an intrauterine infection model in the postpartum dairy cow.

AIMS: To develop an intrauterine infection model for Trueperella pyogenes in postpartum dairy cows and to assess the effect of this infection on the degree of intrauterine inflammation and concentrations of progesterone in serum. METHODS: The oestrous cycles of 36 healthy, non-pregnant, postpartum dairy cows were synchronised. They were then treated by intrauterine infusion of 0.5 g cephapirin before being blocked by age and randomly assigned to treatment with intrauterine infusion of saline (n = 18), 107 (n = 9) or 109 (n = 9) cfu of T. pyogenes, approximately 4 days after the expected time of ovulation (Day 0). Prior to intrauterine infusion on Day 0 and again on Days 3, 7, 10, and 15, cytobrush samples were collected from the uterus of each cow for microbiology and assessment of the percentage of polymorphonuclear neutrophils (PMN%). Blood samples were collected on the same days for measurement of concentrations of progesterone in serum, and uterine lumen diameter was assessed daily using transrectal ultrasonography. RESULTS: Trueperella pyogenes was isolated from 5/18 (28%), 7/9 (78%) and 8/9 (89%) cows infused with saline, 107 or 109 cfu of T. pyogenes, respectively (p < 0.001). Mean PMN% in the control cows did not change over time (p > 0.05), whereas it was higher on Days 7 and 10 than Day 0 in the 107 cfu group, and higher on Days 3 and 10 than Day 0 in the 109 cfu group (p < 0.05). The percentage of observations with uterine lumen diameters >2 mm was higher in cows infused with 107 (29.3 (95% CI = 14.5-44.2)%) or 109 cfu (19.2 (95% CI = 7.0-31.5)%) than in control cows (3.1 (95% CI = 0.1-6.0)%) (p < 0.001). Mean concentrations of progesterone in serum were higher in cows infused with 107 cfu (2.01 (SE 0.19) ng/mL) than cows infused with 109 cfu (1.01 (SE 0.27) ng/mL), with the control group intermediate (1.41 (SE 0.19) ng/mL) (p = 0.03). CONCLUSIONS: Infusion of 107 or 109 cfu of T. pyogenes resulted in the establishment of intrauterine infection in 83% of cows. Infection resulted in increased uterine lumen diameter, and an inflammatory response, i.e. elevated PMN%. CLINICAL RELEVANCE: This intrauterine infection model may be useful for future research on, for example, the pathogenesis of intrauterine infection in postpartum dairy cows.

The Developmental Chronnecto-Genomics (Dev-CoG) study: A multimodal study on the developing brain.

Brain development has largely been studied through unimodal analysis of neuroimaging data, providing independent results for structural and functional data. However, structure clearly impacts function and vice versa, pointing to the need for performing multimodal data collection and analysis to improve our understanding of brain development, and to further inform models of typical and atypical brain development across the lifespan. Ultimately, such models should also incorporate genetic and epigenetic mechanisms underlying brain structure and function, although currently this area is poorly specified. To this end, we are reporting here a multi-site, multi-modal dataset that captures cognitive function, brain structure and function, and genetic and epigenetic measures to better quantify the factors that influence brain development in children originally aged 9-14 years. Data collection for the Developmental Chronnecto-Genomics (Dev-CoG) study (http://devcog.mrn.org/) includes cognitive, emotional, and social performance scales, structural and functional MRI, diffusion MRI, magnetoencephalography (MEG), and saliva collection for DNA analysis of single nucleotide polymorphisms (SNPs) and DNA methylation patterns. Across two sites (The Mind Research Network and the University of Nebraska Medical Center), data from over 200 participants were collected and these children were re-tested annually for at least 3 years. The data collection protocol, sample demographics, and data quality measures for the dataset are presented here. The sample will be made freely available through the collaborative informatics and neuroimaging suite (COINS) database at the conclusion of the study.