bluuebunny/crossref_metadata_2025_split huggingface dataset:
Social and emotional characteristics of girls and young women withDDX3X-linked intellectual disability: A descriptive and comparative study
Authors: Ng-Cordell Elise , Kolesnik-Taylor Anna , O’Brien Sinéad , Astle Duncan , Scerif Gaia , Baker Kate 
Published: September 2021

AbstractBackgroundDDX3Xvariants are a common cause of intellectual disability (ID) in females. Previous studies have reported high rates of autism spectrum disorder and emotional-behavioural difficulties within this group. However, no study has compared social and emotional characteristics in individuals withDDX3Xvariants to individuals with other monogenic causes of ID.MethodsTwenty-three females with pathogenic or likely pathogenicDDX3Xvariants were recruited via UK regional genetics centres, genetic research cohorts, and family support groups. Twenty-three females with ID and variants in other genes were recruited via the same routes. Phenotypic data were collected through semi-structured interviews and standardised questionnaires.ResultsIn line with previous research, we found a wide range of adaptive, social and emotional function within theDDX3Xgroup. Autism characteristics assessed via the Social Responsiveness Scale (SRS) did not differ betweenDDX3Xand comparison groups, while levels of anxiety and self-injurious behaviour (SIB) scores assessed via the Developmental Behaviour Checklist (DBC) were significantly higher in theDDX3Xgroup. Autistic characteristics, anxiety and SIB scores were positively correlated within theDDX3Xgroup. Individuals withDDX3Xmissense variants had poorer adaptive abilities than those with protein truncating variants as previously reported, butDDX3Xvariant type did not significantly predict emotional and behavioural characteristics.ConclusionsWe provide quantitative evidence that overall incidence of autistic characteristics is not higher amongst girls and women withDDX3Xvariants than expected for ID. However, theDDX3Xgroup demonstrates more SIBs and anxiety symptoms than expected, with close relationships between SIBs and anxiety, and between anxiety and autistic characteristics. Future work is warranted to explore the multilevel mechanisms contributing to social and emotional development in individuals withDDX3Xvariants, and consider whether these mechanisms are specific to this genetic diagnosis or shared with a subset of people with ID due to other causes.
Real-Time Semi-Automated and Automated Voxel Placement for Repeated Acquisition Magnetic Resonance Spectroscopy
Authors: Bishop James H. , Geoly Andrew , Khan Naushaba , Tischler Claudia , Krueger Ruben , Amin Heer , Baltusis Laima , Wu Hua , Spiegel David , Williams Nolan , Sacchet Matthew D. 
Published: September 2021

ABSTRACTMagnetic resonance spectroscopy (MRS) is heavily dependent on the investigative team to prescribe, or demarcate, the desired tissue volume-of-interest. Manual prescription, the current standard in the field, requires expertise in neuroanatomy to ensure spatial consistency within and across subjects. Spatial precision of MRS voxel placement thus presents challenges for cross-sectional studies, and even more so for repeated-measure and multi-acquisition designs. Furthermore, voxel prescriptions based-solely on anatomical landmarks may not be ideal in regions with substantial functional and cytoarchitectural variability or to examine individualized/targeted interventions. Here we propose and validate robust and real-time methods to automate MRS voxel placement using functionally defined coordinates within the left dorsolateral prefrontal cortex in clinical cohorts of chronic pain and depression. We hypothesized that increased automation would produce more consistent voxel placement across repeated acquisitions particularly in reference to standard manual prescription. Data were collected and analyzed using two independent prospective transcranial magnetic stimulation studies: 1) a single-day multi-session sandwich design and 2) a longitudinal design. Participants with fibromyalgia syndrome (N=50) and major depressive disorder (N=35) underwent MRI as part of ongoing clinical studies. MEGA-PRESS and Optimized-PRESS MRS acquisitions were acquired at 3-tesla. Evaluation of the reproducibility of spatial location and tissue segmentation was assessed for: 1) manual, 2) semi-automated, and 3) automated voxel prescription approaches. Variability of grey and white matter voxel tissue composition was reduced using automated placement protocols as confirmed by common MRS software processing pipelines (Gannet; SPM-based segmentation) and via Freesurfer-based segmentation. Spatially, post-to pre-voxel center-of-gravity distance was reduced and voxel overlap increased significantly across datasets using automated compared to manual procedures. These results demonstrate the within subject reliability and reproducibility of a method for reducing variability introduced by spatial inconsistencies during MRS acquisitions. The proposed method is a meaningful advance toward improved consistency of MRS data in neuroscience and can be leveraged for multi-session and longitudinal studies that target precisely defined regions-of-interest via a coordinate-based approach.
Effectiveness of COVID-19 vaccines against SARS-CoV-2 variants of concern: a systematic review and meta-analysis
Authors: Zeng Baoqi , Gao Le , Zhou Qingxin , Yu Kai , Sun Feng 
Published: September 2021

ABSTRACTBackgroundIt was urgent and necessary to synthesize the evidence for vaccine effectiveness (VE) against SARS-CoV-2 variants of concern (VOC). We conducted a systematic review and meta-analysis to provide a comprehensive overview of the effectiveness profile of COVID-19 vaccines against VOC.MethodsPublished and preprinted randomized controlled trials (RCTs), cohort studies, and case-control studies that evaluated the VE against VOC (Alpha, Beta, Gamma, or Delta) were searched until 31 August 2021. Pooled estimates and 95% confidence intervals (CIs) were calculated using random-effects meta-analysis. VE was defined as (1− estimate).ResultsSeven RCTs (51,169 participants), 10 cohort studies (14,385,909 participants) and 16 case-control studies (734,607 cases) were included. Eight COVID-19 vaccines (mRNA-1273, BNT162b2, ChAdOx1, Ad26.COV2.S, NVX-CoV2373, BBV152, CoronaVac, and BBIBP-CorV) were included in this analysis. Full vaccination was effective against Alpha, Beta/Gamma, and Delta variants, with VE of 88.3% (95% CI, 82.4–92.2), 70.7% (95% CI, 59.9–78.5), and 71.6% (95% CI, 64.1–77.4), respectively. But partial vaccination was less effective, with VE of 59.0% (95% CI, 51.3–65.5), 49.3% (95% CI, 33.0–61.6), and 52.6% (95% CI, 43.3–60.4), respectively. mRNA vaccines seemed to have higher VE against VOC over others, significant interactions (pinteraction< 0.10) were observed between VE and vaccine type (mRNA vaccines vs. non-mRNA vaccines).ConclusionsFull vaccination of COVID-19 vaccines is highly effective against Alpha variant, and moderate effective against Beta/Gamma and Delta variants. Partial vaccination has less VE against VOC. mRNA vaccines seem to have higher VE against Alpha, Beta/Gamma, and Delta variants over others.
Mechanical characterisation of the developing cell wall layers of tension wood fibres by Atomic Force Microscopy
Authors: Arnould Olivier , Capron Marie , Ramonda Michel , Laurans Françoise , Alméras Tancrède , Pilate Gilles , Clair Bruno 
Published: September 2021

AbstractTrees generate mechanical stresses at periphery of stem and branches to improve their strength and to control the orientation of their axes. This key factor in the biomechanical design of trees, named “maturation stress”, occurs in wood fibres during cellular maturation when their secondary cell wall thickens. In this study, the spatial and temporal stiffening kinetics of the different cell wall layers were recorded during fibre maturation on a sample of poplar tension wood using atomic force microscopy. The thickening of the different layers was also recorded. The stiffening of the CML, S1 and S2-layers was initially synchronous with the thickening of the S2-layer and continued a little after the S2-layer reached its final thickness as the G-layer began to develop. In contrast, the global stiffness of the G-layer, which initially increased with its thickening, was close to stable long before it reached its final maximum thickness. A limited radial gradient of stiffness was observed in the G-layer, but it decreased sharply on the lumen side, where the new sub-layers are deposited during cell wall thickening. Although very similar at the ultrastructural and biochemical levels, the stiffening kinetics of the poplar G-layer appears to be very different from that described in maturing bast fibres.
T cells modulate the microglial response to brain ischemia
Authors: Benakis Corinne , Simats Alba , Tritschler Sophie , Heindl Steffanie , Besson-Girard Simon , Llovera Gemma , Pinkham Kelsey , Kolz Anna , Theis Fabian , Gökce Özgün , Peters Anneli , Liesz Arthur 
Published: September 2021

AbstractNeuroinflammation after stroke is characterized by the activation of resident microglia and the invasion of circulating leukocytes into the brain. Although lymphocytes infiltrate the brain in small number, they have been consistently demonstrated to be the most potent leukocyte subpopulation contributing to secondary inflammatory brain injury. However, the exact mechanism how this minimal number of lymphocytes can profoundly affect stroke outcome is still largely elusive. Here, using a mouse model for ischemic stroke, we demonstrated that early activation of microglia in response to stroke is differentially regulated by distinct T cell subpopulations. Acute treatment with engineered T cells overexpressing IL-10 administered into the cisterna magna after stroke induces a switch of microglial gene expression to a profile associated with pro-regenerative functions. These findings substantiate the role of T cells in stroke with large impact on the cerebral inflammatory milieu by polarizing the microglial phenotype. Targeting T cell-microglia interactions can have direct translational relevance for further development of immune-targeted therapies for stroke and other neuroinflammatory conditions.SummaryThe crosstalk between brain infiltrating T cells and microglia in response to stroke remains elusive. Benakis et al. report that transcriptional signature of the stroke-associated microglia is reprogrammed by distinct T cell subpopulations. Engineered T cells overexpressing IL-10 administered four hours after stroke reinitiate microglial function inducing a pro-regenerative environment.
Normative and mechanistic model of an adaptive circuit for efficient encoding and feature extraction
Authors: Chapochnikov Nikolai M. , Pehlevan Cengiz , Chklovskii Dmitri B. 
Published: September 2021

AbstractOne major question in neuroscience is how to relate connectomes to neural activity, circuit function, and learning. We offer an answer in the peripheral olfactory circuit of the Drosophila larva, composed of olfactory receptor neurons (ORNs) connected through feedback loops with interconnected inhibitory local neurons (LNs). We combine structural and activity data and, using a holistic normative framework based on similarity-matching, we propose a biologically plausible mechanistic model of the circuit. Our model predicts the ORN → LN synaptic weights found in the connectome and demonstrate that they reflect correlations in ORN activity patterns. Additionally, our model explains the relation between ORN → LN and LN – LN synaptic weight and the arising of different LN types. This global synaptic organization can autonomously arise through Hebbian plasticity, and thus allows the circuit to adapt to different environments in an unsupervised manner. Functionally, we propose LNs extract redundant input correlations and dampen them in ORNs, thus partially whitening and normalizing the stimulus representations in ORNs. Our work proposes a comprehensive framework to combine structure, activity, function, and learning, and uncovers a general and potent circuit motif that can learn and extract significant input features and render stimulus representations more efficient.SignificanceThe brain represents information with patterns of neural activity. At the periphery, due to the properties of the external world and of encoding neurons, these patterns contain correlations, which are detrimental for stimulus discrimination. We study the peripheral olfactory neural circuit of the Drosophila larva, that preprocesses neural representations before relaying them to higher brain areas. A comprehensive understanding of this preprocessing is, however, lacking. Here, we propose a mechanistic and normative framework describing the function of the circuit and predict the circuit’s synaptic organization based on the circuit’s input neural activity. We show how the circuit can autonomously adapt to different environments, extracts stimulus features, and decorrelate and normalize input representations, which facilitates odor discrimination downstream.
Express Arm Responses Appear Bilaterally on Upper-limb Muscles in an Arm Choice Reaching Task
Authors: Kearsley Sarah L. , Cecala Aaron L. , Kozak Rebecca A. , Corneil Brian D. 
Published: September 2021

AbstractWhen required, humans can generate very short latency reaches towards visual targets, like catching a falling cellphone. During such rapid reaches, express arm responses are the first wave of upper limb muscle recruitment, occurring ~80-100 ms after target appearance. There is accumulating evidence that express arm responses arise from signaling along the tecto-reticulo-spinal tract, but the involvement of the reticulo-spinal tract has not been well-studied. Since the reticulospinal tract projects bilaterally, we studied whether express arm responses would be generated bilaterally. Human participants (n = 14; 7 female) performed visually guided reaches in a modified emerging target paradigm where either arm could intercept the target. We recorded electromyographic activity bilaterally from the pectoralis major muscle. Our analysis focused on target locations where participants reached with the right arm on some trials, and the left arm on others. In support of the involvement of the reticulospinal tract, express arm responses persisted bilaterally regardless of which arm reached to the target. The latency and magnitude of the express arm response did not depend on whether the arm was chosen to reach or not. However, on the reaching arm, the magnitude of the express arm response was correlated to the level of anticipatory activity. The bilateral generation of express arm responses supports the involvement of the reticulo-spinal tract. We surmise that the correlation between anticipatory activity and the magnitude of express arm responses on the reaching arm arises from convergence of cortically-derived signals with a parallel subcortical pathway mediating the express arm response.New and NoteworthyExpress arm responses have been proposed to arise from the tecto-reticulo-spinal tract originating within the superior colliculus, but the involvement of the reticulo-spinal tract has not been well studied. Here, we show these responses appear bilaterally in a task where either arm can reach to a newly appearing stimulus. Our results suggest that the most rapid visuomotor transformations for reaching are performed by a subcortical pathway.
Emergent selectivity for scenes, object properties, and contour statistics in feedforward models of scene-preferring cortex
Authors: Li Donald Shi Pui , Bonner Michael F. 
Published: September 2021

ABSTRACTThe scene-preferring portion of the human ventral visual stream, known as the parahippocampal place area (PPA), responds to scenes and landmark objects, which tend to be large in real-world size, fixed in location, and inanimate. However, the PPA also exhibits preferences for low-level contour statistics, including rectilinearity and cardinal orientations, that are not directly predicted by theories of scene- and landmark-selectivity. It is unknown whether these divergent findings of both low- and high-level selectivity in the PPA can be explained by a unified computational theory. To address this issue, we fit feedforward computational models of visual feature coding to the image-evoked fMRI responses of the PPA, and we performed a series of high-throughput experiments on these models. Our findings show that feedforward models of the PPA exhibit emergent selectivity across multiple levels of complexity, giving rise to seemingly high-level preferences for scenes and for objects that are large, spatially fixed, and inanimate/manmade while simultaneously yielding low-level preferences for rectilinear shapes and cardinal orientations. These results reconcile disparate theories of PPA function in a unified model of feedforward feature coding, and they demonstrate how multifaceted selectivity profiles naturally emerge from the feedforward computations of visual cortex and the natural statistics of images.SIGNIFICANCE STATEMENTVisual neuroscientists characterize cortical selectivity by identifying stimuli that drive regional responses. A perplexing finding is that many higher-order visual regions exhibit selectivity profiles spanning multiple levels of complexity: they respond to highly complex categories, such as scenes and landmarks, but also to surprisingly simplistic features, such as specific contour orientations. Using large-scale computational analyses and human brain imaging, we show how multifaceted selectivity in scene-preferring cortex can emerge from the feedforward, hierarchical coding of visual features. Our work reconciles seemingly divergent findings of selectivity in scene-preferring cortex and suggests that surprisingly simple feedforward feature representations may be central to the category-selective organization of the human visual system.
Transcriptome-wide association and prediction for carotenoids and tocochromanols in fresh sweet corn kernels
Authors: Hershberger Jenna , Tanaka Ryokei , Wood Joshua C. , Kaczmar Nicholas , Wu Di , Hamilton John P. , DellaPenna Dean , Buell C. Robin , Gore Michael A. 
Published: September 2021

ABSTRACTSweet corn is consistently one of the most highly consumed vegetables in the U.S., providing a valuable opportunity to increase nutrient intake through biofortification. Significant variation for carotenoid (provitamin A, lutein, zeaxanthin) and tocochromanol (vitamin E, antioxidants) levels is present in temperate sweet corn germplasm, yet previous genome-wide association studies (GWAS) of these traits have been limited by low statistical power and mapping resolution. Here, we employed a high-quality transcriptomic dataset collected from fresh sweet corn kernels to conduct transcriptome-wide association studies (TWAS) and transcriptome prediction studies for 39 carotenoid and tocochromanol traits. In agreement with previous GWAS findings, TWAS detected significant associations for four causal genes,β-carotene hydroxylase (crtRB1),lycopene epsilon cyclase(lcyE),γ-tocopherol methyltransferase(vte4), andhomogentisate geranylgeranyltransferase(hggt1) on a transcriptome-wide level. Pathway-level analysis revealed additional associations fordeoxy-xylulose synthase2(dxs2),diphosphocytidyl methyl erythritol synthase2(dmes2),cytidine methyl kinase1(cmk1), andgeranylgeranyl hydrogenase1(ggh1), of which,dmes2, cmk1, andggh1have not previously been identified through maize association studies. Evaluation of prediction models incorporating genome-wide markers and transcriptome-wide abundances revealed a trait-dependent benefit to the inclusion of both genomic and transcriptomic data over solely genomic data, but both transcriptome- and genome-wide datasets outperformeda prioricandidate gene-targeted prediction models for most traits. Altogether, this study represents an important step towards understanding the role of regulatory variation in the accumulation of vitamins in fresh sweet corn kernels.Core IdeasTranscriptomic data aid the study of vitamin levels in fresh sweet corn kernels.crtRB1, lcyE, dxs2, dmes2, andcmk1were associated with carotenoid traits.vte4, hggt1, andggh1were associated with tocochromanol traits.Transcriptomic data boosted predictive ability over genomic data alone for some traits.Joint transcriptome- and genome-wide models achieved the highest predictive abilities.
Single-cell RNA Sequencing Reveals Immunosuppressive Myeloid Cell Diversity and Restricted Cytotoxic Effector Cell Trafficking and Activation During Malignant Progression in Glioma
Authors: Rajendran Sakthi , Peterson Clayton , Canella Alessandro , Hu Yang , Gross Amy , Cam Maren , Serin-Harmanci Akdes , Distefano Rosario , Nigita Giovanni , Wang Wesley , Miller Katherine E. , Elemento Olivier , Roberts Ryan , Holland Eric C. , Rao Ganesh , Mardis Elaine R. , Rajappa Prajwal 
Published: September 2021

ABSTRACTLow grade gliomas (LGG) account for about two-thirds of all glioma diagnoses in adolescents and young adults (AYA) and malignant progression of these patients leads to dismal outcomes. Recent studies have shown the importance of the dynamic tumor microenvironment in high-grade gliomas (HGG), yet its role is still poorly understood in low-grade glioma malignant progression. Here, we investigated the heterogeneity of the immune microenvironment using a platelet-derived growth factor (PDGF)-driven RCAS (replication-competent ASLV long terminal repeat with a splice acceptor) glioma model that recapitulates the malignant progression of low to high-grade glioma in humans and also provides a model system to characterize immune cell trafficking and evolution. To illuminate changes in the immune cell landscape during tumor progression, we performed single-cell RNA sequencing on immune cells isolated from animals bearing no tumor (NT), LGG and HGG, with a particular focus on the myeloid cell compartment, which is known to mediate glioma immunosuppression. LGGs demonstrated significantly increased infiltrating T cells, CD4 T cells, CD8 T cells, B cells, and natural killer cells in the tumor microenvironment, whereas HGGs significantly abrogated this infiltration. Our study identified two distinct macrophage clusters in the tumor microenvironment; one cluster appeared to be bone marrow-derived while another was defined by overexpression of Trem2, a marker of tumor associated macrophages. Our data demonstrates that these two distinct macrophage clusters show an immune-activated phenotype (Stat1, Tnf, Cxcl9 and Cxcl10) in LGG which evolves to an immunosuppressive state (Lgals3, Apoc1 and Id2) in HGG that restricts T cell recruitment and activation. We identified CD74 and macrophage migration inhibition factor (MIF) as potential targets for these distinct macrophage populations. Interestingly, these results were mirrored by our analysis of the TCGA dataset, which demonstrated a statistically significant association between CD74 overexpression and decreased overall survival in AYA patients with grade II gliomas. Targeting immunosuppressive myeloid cells and intra-tumoral macrophages within this therapeutic window may ameliorate mechanisms associated with immunosuppression before and during malignant progression.