Feature similarity gradients detect alterations in the neonatal cortex associated with preterm birth.

The early life environment programmes cortical architecture and cognition across the life course. A measure of cortical organisation that integrates information from multimodal MRI and is unbound by arbitrary parcellations has proven elusive, which hampers efforts to uncover the perinatal origins of cortical health. Here, we use the Vogt-Bailey index to provide a fine-grained description of regional homogeneities and sharp variations in cortical microstructure based on feature gradients, and we investigate the impact of being born preterm on cortical development at term-equivalent age. Compared with term-born controls, preterm infants have a homogeneous microstructure in temporal and occipital lobes, and the medial parietal, cingulate, and frontal cortices, compared with term infants. These observations replicated across two independent datasets and were robust to differences that remain in the data after matching samples and alignment of processing and quality control strategies. We conclude that cortical microstructural architecture is altered in preterm infants in a spatially distributed rather than localised fashion.

Usage of mineralocorticoids and isotonic crystalloids in subarachnoid hemorrhage patients in the United States.

BACKGROUND: The usage rates of mineralocorticoids (fludrocortisone) to treat hyponatremia and isotonic crystalloids (saline and balanced crystalloids) to maintain intravascular volume in patients with aneurysmal subarachnoid hemorrhage (aSAH) patients across the United States are unknown. METHODS: We surveyed National Institute of Neurologic Disorders and Stroke (NINDS) StrokeNet sites in 2023, which are mostly large, tertiary, academic centers, and analyzed subarachnoid hemorrhage encounters from 2010 to 2020 in the Premier Healthcare Database that is representative of all types of hospitals and captures about 20 % of all acute inpatient care in the United States. RESULTS: Although mineralocorticoids are used by 70 % of the NINDS StrokeNet sites, it is used in less than 20 % of the aSAH encounters in the Premier Database. Although saline is ubiquitously used, balanced crystalloids are increasingly used for fluid therapy in aSAH patients. Its use in the NINDS StrokeNet sites and the Premier Healthcare Database is 41 and 45 %, respectively. CONCLUSIONS: The use of mineralocorticoids remains low, and balanced crystalloids are increasingly used as fluid therapy in aSAH patients. The effectiveness of mineralocorticoids and balanced crystalloids in improving outcomes for aSAH patients must be rigorously tested in randomized clinical trials.

Usage of Mineralocorticoids and Isotonic Crystalloids in Subarachnoid Hemorrhage Patients in the United States.

Background: The usage rates of mineralocorticoids (fludrocortisone) to treat hyponatremia and isotonic crystalloids (saline and balanced crystalloids) to maintain intravascular volume in patients with aneurysmal subarachnoid hemorrhage (aSAH) patients across the United States are unknown. Methods: We surveyed National Institute of Neurologic Disorders and Stroke (NINDS) StrokeNet sites, which are mostly large, tertiary, academic centers, and analyzed subarachnoid hemorrhage encounters in the Premier Healthcare Database that is representative of all types of hospitals and captures about 20% of all acute inpatient care in the United States. Results: Although mineralocorticoids are used by 70% of the NINDS StrokeNet sites in aSAH patients, it is used in less than 25% of the aSAH encounters in the Premier Database. Although saline is ubiquitously used, balanced crystalloids are increasingly used for fluid therapy in aSAH patients. Its use in the NINDS StrokeNet sites and the Premier Healthcare Database is 41% and 45%, respectively. Conclusions: The use of mineralocorticoids remains low, and balanced crystalloids are increasingly used as fluid therapy in aSAH patients. The effectiveness of mineralocorticoids and balanced crystalloids in improving outcomes for aSAH patients must be rigorously tested in randomized clinical trials.

BOUNTI: Brain vOlumetry and aUtomated parcellatioN for 3D feTal MRI.

Fetal MRI is widely used for quantitative brain volumetry studies. However, currently, there is a lack of universally accepted protocols for fetal brain parcellation and segmentation. Published clinical studies tend to use different segmentation approaches that also reportedly require significant amounts of time-consuming manual refinement. In this work, we propose to address this challenge by developing a new robust deep learning-based fetal brain segmentation pipeline for 3D T2w motion corrected brain images. At first, we defined a new refined brain tissue parcellation protocol with 19 regions-of-interest using the new fetal brain MRI atlas from the Developing Human Connectome Project. This protocol design was based on evidence from histological brain atlases, clear visibility of the structures in individual subject 3D T2w images and the clinical relevance to quantitative studies. It was then used as a basis for developing an automated deep learning brain tissue parcellation pipeline trained on 360 fetal MRI datasets with different acquisition parameters using semi-supervised approach with manually refined labels propagated from the atlas. The pipeline demonstrated robust performance for different acquisition protocols and GA ranges. Analysis of tissue volumetry for 390 normal participants (21-38 weeks gestational age range), scanned with three different acquisition protocols, did not reveal significant differences for major structures in the growth charts. Only minor errors were present in < 15% of cases thus significantly reducing the need for manual refinement. In addition, quantitative comparison between 65 fetuses with ventriculomegaly and 60 normal control cases were in agreement with the findings reported in our earlier work based on manual segmentations. These preliminary results support the feasibility of the proposed atlas-based deep learning approach for large-scale volumetric analysis. The created fetal brain volumetry centiles and a docker with the proposed pipeline are publicly available online at https://hub.docker.com/r/fetalsvrtk/segmentation (tag brain_bounti_tissue).

Structural and functional asymmetry of the neonatal cerebral cortex.

Features of brain asymmetry have been implicated in a broad range of cognitive processes; however, their origins are still poorly understood. Here we investigated cortical asymmetries in 442 healthy term-born neonates using structural and functional magnetic resonance images from the Developing Human Connectome Project. Our results demonstrate that the neonatal cortex is markedly asymmetric in both structure and function. Cortical asymmetries observed in the term cohort were contextualized in two ways: by comparing them against cortical asymmetries observed in 103 preterm neonates scanned at term-equivalent age, and by comparing structural asymmetries against those observed in 1,110 healthy young adults from the Human Connectome Project. While associations with preterm birth and biological sex were minimal, significant differences exist between birth and adulthood.

Telomere length and brain imaging phenotypes in UK Biobank.

Telomeres form protective caps at the ends of chromosomes, and their attrition is a marker of biological aging. Short telomeres are associated with an increased risk of neurological and psychiatric disorders including dementia. The mechanism underlying this risk is unclear, and may involve brain structure and function. However, the relationship between telomere length and neuroimaging markers is poorly characterized. Here we show that leucocyte telomere length (LTL) is associated with multi-modal MRI phenotypes in 31,661 UK Biobank participants. Longer LTL is associated with: i) larger global and subcortical grey matter volumes including the hippocampus, ii) lower T1-weighted grey-white tissue contrast in sensory cortices, iii) white-matter microstructure measures in corpus callosum and association fibres, iv) lower volume of white matter hyperintensities, and v) lower basal ganglia iron. Longer LTL was protective against certain related clinical manifestations, namely all-cause dementia (HR 0.93, 95% CI: 0.91-0.96), but not stroke or Parkinson's disease. LTL is associated with multiple MRI endophenotypes of neurodegenerative disease, suggesting a pathway by which longer LTL may confer protective against dementia.

The Multiscale Surface Vision Transformer.

Surface meshes are a favoured domain for representing structural and functional information on the human cortex, but their complex topology and geometry pose significant challenges for deep learning analysis. While Transformers have excelled as domain-agnostic architectures for sequence-to-sequence learning, notably for structures where the translation of the convolution operation is non-trivial, the quadratic cost of the self-attention operation remains an obstacle for many dense prediction tasks. Inspired by some of the latest advances in hierarchical modelling with vision transformers, we introduce the Multiscale Surface Vision Transformer (MS-SiT) as a backbone architecture for surface deep learning. The self-attention mechanism is applied within local-mesh-windows to allow for high-resolution sampling of the underlying data, while a shifted-window strategy improves the sharing of information between windows. Neighbouring patches are successively merged, allowing the MS-SiT to learn hierarchical representations suitable for any prediction task. Results demonstrate that the MS-SiT outperforms existing surface deep learning methods for neonatal phenotyping prediction tasks using the Developing Human Connectome Project (dHCP) dataset. Furthermore, building the MS-SiT backbone into a U-shaped architecture for surface segmentation demonstrates competitive results on cortical parcellation using the UK Biobank (UKB) and manually-annotated MindBoggle datasets. Code and trained models are publicly available at https://github.com/metrics-lab/surface-vision-transformers.

Antimony nanobelt asymmetric membranes for sodium ion battery.

In this study, composite asymmetric membranes containing antimony (Sb) nanobelts are prepared via a straightforward phase inversion method in combination with post-pyrolysis treatment. Sb nanobelt asymmetric membranes demonstrate improved cyclability and specific capacity as the alloy anode of sodium ion battery compared to Sb nanobelt thin films without asymmetric porous structure. The unique structure can effectively accommodate the large volume expansion of Sb-based alloy anodes, prohibit the loss of fractured active materials, and aid in the formation of stable artificial solid electrolyte interphases as evidenced by an outstanding capacity retention of ∼98% in 130 cycles at 60 mA g-1. A specific capacity of ∼600 mAh g-1is obtained at 15 mA g-1(1/40C). When the current density is increased to 240 mA g-1, ∼80% capacity can be maintained (∼480 mAh g-1). The relations among phase inversion conditions, structures, compositions, and resultant electrochemical properties are revealed through comprehensive characterization.

ICAM-Reg: Interpretable Classification and Regression With Feature Attribution for Mapping Neurological Phenotypes in Individual Scans.

An important goal of medical imaging is to be able to precisely detect patterns of disease specific to individual scans; however, this is challenged in brain imaging by the degree of heterogeneity of shape and appearance. Traditional methods, based on image registration, historically fail to detect variable features of disease, as they utilise population-based analyses, suited primarily to studying group-average effects. In this paper we therefore take advantage of recent developments in generative deep learning to develop a method for simultaneous classification, or regression, and feature attribution (FA). Specifically, we explore the use of a VAE-GAN (variational autoencoder - general adversarial network) for translation called ICAM, to explicitly disentangle class relevant features, from background confounds, for improved interpretability and regression of neurological phenotypes. We validate our method on the tasks of Mini-Mental State Examination (MMSE) cognitive test score prediction for the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, as well as brain age prediction, for both neurodevelopment and neurodegeneration, using the developing Human Connectome Project (dHCP) and UK Biobank datasets. We show that the generated FA maps can be used to explain outlier predictions and demonstrate that the inclusion of a regression module improves the disentanglement of the latent space. Our code is freely available on GitHub https://github.com/CherBass/ICAM.

A bipolar taxonomy of adult human brain sulcal morphology related to timing of fetal sulcation and trans-sulcal gene expression gradients.

We developed a computational pipeline (now provided as a resource) for measuring morphological similarity between cortical surface sulci to construct a sulcal phenotype network (SPN) from each magnetic resonance imaging (MRI) scan in an adult cohort (N=34,725; 45-82 years). Networks estimated from pairwise similarities of 40 sulci on 5 morphological metrics comprised two clusters of sulci, represented also by the bipolar distribution of sulci on a linear-to-complex dimension. Linear sulci were more heritable and typically located in unimodal cortex; complex sulci were less heritable and typically located in heteromodal cortex. Aligning these results with an independent fetal brain MRI cohort (N=228; 21-36 gestational weeks), we found that linear sulci formed earlier, and the earliest and latest-forming sulci had the least between-adult variation. Using high-resolution maps of cortical gene expression, we found that linear sulcation is mechanistically underpinned by trans-sulcal gene expression gradients enriched for developmental processes.

Future Prospects for Epigenetics in Autism Spectrum Disorder.

Despite decades of investigation into the genetics of autism spectrum disorder (ASD), a current consensus in the field persists that ASD risk is too heterogeneous to be diagnosed by a single set of genetic variants. As such, ASD research has broadened to include assessment of other molecular biomarkers implicated in the condition that may be reflective of environmental exposures or gene by environment interactions. Epigenetic variance, and specifically differential DNA methylation, have emerged as areas of particularly high interest to ASD, as the epigenetic markers from specific chromatin loci collectively can reflect influences of multiple genetic and environmental factors and can also result in differential gene expression patterns. This review examines recent studies of the ASD epigenome, detailing common gene pathways found to be differentially methylated in people with ASD, and considers how these discoveries may inform our understanding of ASD etiology. We also consider future applications of epigenetics in ASD research and clinical practice, focusing on substratification, biomarker development, and experimental preclinical models of ASD that test causality. In combination with other -omics approaches, epigenomics allows an improved conceptualization of the multifactorial nature of ASD, and opens future lines of inquiry for both basic research and clinical practice.

Placental methylome reveals a 22q13.33 brain regulatory gene locus associated with autism.

BACKGROUND: Autism spectrum disorder (ASD) involves complex genetics interacting with the perinatal environment, complicating the discovery of common genetic risk. The epigenetic layer of DNA methylation shows dynamic developmental changes and molecular memory of in utero experiences, particularly in placenta, a fetal tissue discarded at birth. However, current array-based methods to identify novel ASD risk genes lack coverage of the most structurally and epigenetically variable regions of the human genome. RESULTS: We use whole genome bisulfite sequencing in placenta samples from prospective ASD studies to discover a previously uncharacterized ASD risk gene, LOC105373085, renamed NHIP. Out of 134 differentially methylated regions associated with ASD in placental samples, a cluster at 22q13.33 corresponds to a 118-kb hypomethylated block that replicates in two additional cohorts. Within this locus, NHIP is functionally characterized as a nuclear peptide-encoding transcript with high expression in brain, and increased expression following neuronal differentiation or hypoxia, but decreased expression in ASD placenta and brain. NHIP overexpression increases cellular proliferation and alters expression of genes regulating synapses and neurogenesis, overlapping significantly with known ASD risk genes and NHIP-associated genes in ASD brain. A common structural variant disrupting the proximity of NHIP to a fetal brain enhancer is associated with NHIP expression and methylation levels and ASD risk, demonstrating a common genetic influence. CONCLUSIONS: Together, these results identify and initially characterize a novel environmentally responsive ASD risk gene relevant to brain development in a hitherto under-characterized region of the human genome.

Preterm birth alters the development of cortical microstructure and morphology at term-equivalent age.

INTRODUCTION: The dynamic nature and complexity of the cellular events that take place during the last trimester of pregnancy make the developing cortex particularly vulnerable to perturbations. Abrupt interruption to normal gestation can lead to significant deviations to many of these processes, resulting in atypical trajectory of cortical maturation in preterm birth survivors. METHODS: We sought to first map typical cortical micro- and macrostructure development using invivo MRI in a large sample of healthy term-born infants scanned after birth (n = 259). Then we offer a comprehensive characterization of the cortical consequences of preterm birth in 76 preterm infants scanned at term-equivalent age (37-44 weeks postmenstrual age). We describe the group-average atypicality, the heterogeneity across individual preterm infants, and relate individual deviations from normative development to age at birth and neurodevelopment at 18 months. RESULTS: In the term-born neonatal brain, we observed heterogeneous and regionally specific associations between age at scan and measures of cortical morphology and microstructure, including rapid surface expansion, greater cortical thickness, lower cortical anisotropy and higher neurite orientation dispersion. By term-equivalent age, preterm infants had on average increased cortical tissue water content and reduced neurite density index in the posterior parts of the cortex, and greater cortical thickness anteriorly compared to term-born infants. While individual preterm infants were more likely to show extreme deviations (over 3.1 standard deviations) from normative cortical maturation compared to term-born infants, these extreme deviations were highly variable and showed very little spatial overlap between individuals. Measures of regional cortical development were associated with age at birth, but not with neurodevelopment at 18 months. CONCLUSION: We showed that preterm birth alters cortical micro- and macrostructural maturation near the time of full-term birth. Deviations from normative development were highly variable between individual preterm infants.

Quantum signatures for screening metavalent solids.

The objective of this paper is to describe a new data-driven framework for computational screening and discovery of a class of materials termed "metavalent" solids. "Metavalent" solids possess characteristics that are nominally associated with metallic and covalent bonding (in terms of conductivity and coordination numbers) but are distinctly different from both because they show anomalously large response properties and a unique bond-breaking mechanism that is not observed in either covalent or metallic solids. The paper introduces the use of Hirshfeld surface analysis to provide quantum level descriptors that can be used for rapid screening of crystallographic data to identify potentially new "metavalent" solids with novel and emergent properties.

Histopathology after lidocaine/prilocaine cream administration for vulvar biopsy.

BACKGROUND: Case series have described disruptive histopathologic changes following lidocaine/prilocaine cream anesthetic for biopsies. METHODS: A study of histopathologic changes was performed following a randomized trial comparing topical lidocaine/prilocaine cream to 1% lidocaine injection anesthesia for vulvar biopsy. Histopathology was reviewed by two independent dermatopathologists blinded to the type of anesthetic. Specimens were scored on six histopathologic criteria described in the literature. Individual scores for each histopathologic feature and the total score across features were compared between the two groups using marginal models with generalized estimating equations. RESULTS: Of 37 specimens reviewed, 19 were randomized to lidocaine/prilocaine cream and 18 to 1% lidocaine. Subjects exposed to lidocaine/prilocaine had the following odds of histopathologic changes, relative to lidocaine-exposed subjects: acantholysis (odds ratio 2.48; 95% confidence intervals [CI] 0.51, 12.06), clefting (2.42; 0.64, 9.14), pallor/necrosis (1.13; 0.28, 4.50), spongiosis (0.71; 0.18, 2.85), and papillary dermal edema (1.17; 0.41, 3.29). Total scores were not significantly different between treatment arms (risk ratio 0.98; 0.71, 1.35). CONCLUSION: This histopathologic analysis of a randomized trial between lidocaine/prilocaine cream and injected lidocaine as anesthesia for vulvar biopsy shows the absence of significant disruptive histopathologic features secondary to the type of anesthetic. Additional studies in different clinical contexts are warranted.

Low-pressure multipass Raman spectrometer.

Nonintrusive, quantitative measurements of thermodynamic properties of flows associated with propulsion systems are pivotal to advance their design and optimization. Laser-based diagnostics are ideal to provide quantitative results without influencing the flow; however, the environments in which such flows exist are often not conducive for such techniques. Namely, they often lack the optical accessibility required to facilitate the delivery of incident laser radiation and the subsequent collection of induced signals. A particularly challenging, yet crucial, task is to measure thermodynamic properties of plumes issuing from thrusters operating within a vacuum chamber. Large chambers used to simulate the vacuum of space generally lack optical ports that can facilitate complex laser-based measurements. Additionally, the near-vacuum environments within such chambers coupled with the ability of thrusters to efficiently expand the gas flowing through their nozzles lead to plumes with prohibitively low number densities (pressures below 1 Torr). Thus, there is a need to develop a diagnostic system that can offer high throughput without the use of free-space optical ports. Moreover, facilities where propulsion systems are tested typically lack vibrationally isolated space for diagnostic equipment and accurate climate control. As a result, such a high-throughput system must also be compact, versatile, and robust. To this end, the present work describes a fiber-coupled, multipass cell, spontaneous Raman scattering spectroscopy system. This system is intended to provide accurate temperature measurements within low-pressure environments via H2 rotational Raman thermometry. Proof-of-principle measurements are successfully performed at pressures as low as 67 Pa (500 mTorr). Techniques to maintain the signal-to-noise ratio at lower pressures, and the trade-offs associated with them, are discussed and evaluated. Finally, the ability of this system to facilitate additional quantitative measurements is also discussed.

Deep Learning Based Prediction of Perovskite Lattice Parameters from Hirshfeld Surface Fingerprints.

This Letter describes the use of deep learning methods on Hirshfeld surface representations of crystal structure, as an automated means of predicting lattice parameters in cubic inorganic perovskites. While Hirshfeld Surface Analysis is a well-established tool in organic crystallography, we also introduce modified computational protocols for Hirshfeld Surface Analysis tailored specifically to account for nuanced but important differences dealing with inorganic crystals. We demonstrate how two-dimensional Hirshfeld surface fingerprints can serve as a rich "database" of information encoding the complexity of relationships between chemical bonding and bond geometry characteristics of perovskites. Our results are compared with other studies on lattice parameter prediction involving both experimental and computationally derived data, and it is shown that our approach is an improvement over other reported methods. The paper concludes by discussing how this work opens new avenues for data-driven high throughput computational predictions of structure-property relationships involving complex crystal chemistries.

Information sharing in neonatal intensive care: Parental perceptions and preferences.

AIM: Information sharing is a key component of family-centred care, which has traditionally occurred through patient information leaflets. Although patients' access to health information is rapidly changing with internet and mobile technologies, there are few data on parents' perception and preferences for information sharing. Our aim was to evaluate parents' perception of information sharing in neonatal care, to determine parents' preferred medium for health information and to identify priority content for inclusion in a smartphone application. METHODS: Parents at Kidz First Neonatal Care (KFNC) were eligible to take part in our survey, which comprised five sections: (i) demographics, (ii) information in neonatal care, (iii) printed information in neonatal care, (iv) parental views about development of a neonatal smartphone application and (v) general feedback. Parental satisfaction with information sharing in KFNC was assessed with a modified version of the Empowerment of Parents in the Intensive Care-neonatology questionnaire. Descriptive and summary statistics were calculated, and free text data were analysed by content analysis. RESULTS: Forty-one surveys were received, with 62% completed by mothers. Parents were supportive of electronic information, with 88% highly scoring the question 'I would download and use a free neonatal care app'. However, parental views on the need to continue printed material if a neonatal care smartphone application was provided were mixed. Of those parents who provided free-text recommendations, priority content included information about neonatal conditions, preparing for discharge and available supports. CONCLUSION: Parents had positive perceptions of information sharing in neonatal care and were strongly supportive of the introduction of a neonatal phone application.

Lidocaine-Prilocaine Cream Compared With Injected Lidocaine for Vulvar Biopsy: A Randomized Controlled Trial.

OBJECTIVE: To compare pain control during vulvar biopsy after either application of 5% lidocaine-prilocaine cream or injection of 1% lidocaine. METHODS: In a single-site randomized trial, patients who needed vulvar biopsy on a non-hair-bearing surface were recruited from a gynecologic oncology clinic to compare lidocaine-prilocaine cream (placed at least 10 minutes before biopsy) with lidocaine injection (at least 1 minute prior). A sample size of 53 participants in each arm (N=106) was planned. Pain was recorded using a 100 mm visual analog scale at three time points: baseline, after application of anesthesia, and after biopsy. The primary outcome was highest pain score recorded. Secondary outcomes were pain score at biopsy, patient experience, and tolerability and acceptability. Linear regression was used to compare the primary outcome between arms while controlling for baseline vulvar pain. A convenience analysis was performed in March 2019. RESULTS: From October 2018 to March 2019, 38 patients completed informed consent and were randomized. Participants were women with median age of 60 years. Most characteristics between groups were similar. Nineteen were analyzed in the lidocaine-prilocaine group, and 18 were analyzed in the lidocaine injection group. The median highest pain score in the lidocaine-prilocaine group was 20.0 mm vs 56.5 mm in the lidocaine injection group. Controlling for baseline pain, the highest pain score in the lidocaine-prilocaine arm was 25.7 mm lower than in the lidocaine injection arm (95% CI [-45.1 to -6.3]; P<.01). Patients randomized to lidocaine-prilocaine had a significantly better experience than those receiving injected lidocaine (median experience score 2.0 mm vs 17.0 mm; P=.02). CONCLUSION: Lidocaine-prilocaine cream before vulvar biopsy resulted in a lower maximum pain score and a significantly better patient rating of the biopsy experience when compared with lidocaine injection. Lidocaine-prilocaine cream, alone, is a reasonable option to use for vulvar biopsy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03654417.