bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving sleep after stroke: a randomised controlled trial of digital cognitive behavioural therapy for insomnia
Authors: Fleming Melanie K , Smejka Tom , Macey Ellie , Luengo-Fernandez Ramon , Henry Alasdair L , Robinson Barbara , Kyle Simon D , Espie Colin A , Johansen-Berg Heidi 
Published: February 2023

AbstractStroke is frequently accompanied by long-term sleep disruption. We therefore aimed to assess the efficacy of digital cognitive behavioural therapy (dCBT) for insomnia to improve sleep after stroke. A parallel group randomised controlled trial was conducted remotely in participant’s homes/online. Randomisation was online with minimisation of between-group differences in age and baseline Sleep Condition Indicator (SCI-8) score. In total, 86 community dwelling stroke survivors consented, of whom 84 completed baseline assessments (39 female, mean 5.5 years post-stroke, mean 59 years of age) and were randomised to dCBT or control (sleep hygiene information). Follow-up was completed at post-intervention (mean 75 days after baseline) and 8-weeks later. The primary outcome was self-reported insomnia symptoms, as per the SCI-8 (range 0-32, lower numbers indicate more severe insomnia, reliable change 7-points) at post-intervention. There were significant improvements in SCI-8 for dCBT compared to control (intention-to-treat, dCBT n=48, control n=36, 5 imputed datasets, effect of group p≤0.02, ηp2=0.07–0.12, pooled mean difference=-3.35). Additionally, secondary outcomes showed shorter self-reported sleep onset latencies and better mood for the dCBT group, but no significant differences for self-efficacy, quality of life, or actigraphy-derived sleep parameters. Cost-effectiveness analysis found that dCBT dominates over control (non-significant cost savings and higher quality adjusted life years). No related serious adverse events were reported to the researchers. Overall, dCBT for insomnia effectively improves sleep after stroke. Future research is needed to assess earlier stages post-stroke, with a longer follow-up period to determine whether it should be included as part of routine post-stroke care.Clinicaltrials.govNCT04272892
Family Income and Utilization Disparities for Dental Access of Minority Children: A Cross-Sectional Study
Authors: Okuji David , Wei Tianqi , Lee Myeonggyun 
Published: February 2023

AbstractPurposeThrough the use Minorities’ Diminished Return theory, this study aimed to assess the concepts of the theory for access to and utilization of dental care of minority children, compared to White children, when all race/ethnicity groups achieve higher socioeconomic status.MethodsThis study was designed cross-sectionally from 21,599 subjects responding to the 2017 National Survey of Children’s Health. The outcome variables of access to and utilization of dental care were compared across Hispanic and non-Hispanic White, Black, Asian, and Multi-race children. Logistic regression models estimated the effects of race/ethnicity on each outcome, with adjustments for child sex, parental education, child age, and income-to-needs ratio.ResultsThe findings showed that compared to White children, when all racial/ethnic groups increased family income and socioeconomic status, Black and Multi-race children received less health gains in the outcomes of access to and utilization of dental care; and Hispanic children experienced less access to dental care.ConclusionsMinorities’ Diminished Return theory provides evidence of structural barriers which negatively impact the health gains from higher socioeconomic status for access to and utilization of dental care for Black, Hispanic, and Multi-race children. Dentists and policymakers must address systemic racism and structural barriers for oral health equity among all children.
Incorporating data from multiple endpoints in the analysis of clinical trials: example from RSV vaccines
Authors: Prunas Ottavia , Willemsen Joukje E. , Bont Louis , Pitzer Virginia E. , Warren Joshua L. , Weinberger Daniel M. 
Published: February 2023

AbstractBackgroundTo achieve licensure, interventions typically must demonstrate efficacy against a primary outcome in a randomized clinical trial. However, selecting a single primary outcomea prioriis challenging. Incorporating data from multiple and related outcomes might help to increase statistical power in clinical trials. Inspired by real-world clinical trials of interventions against respiratory syncytial virus (RSV), we examined methods for analyzing data on multiple endpoints.MethodWe simulated data from three different populations in which the efficacy of the intervention and the correlation among outcomes varied. We developed a novel permutation-based approach that represents a weighted average of individual outcome test statistics (varP) to evaluate intervention efficacy in a multiple endpoint analysis. We compared the power and type I error rate of this approach to two alternative methods: the Bonferroni correction (bonfT) and another permutation-based approach that uses the minimum P-value across all test statistics (minP).ResultsWhen the vaccine efficacy against different outcomes was similar,VarPyielded higher power thanbonfTandminP;in some scenarios the improvement in power was substantial. In settings where vaccine efficacy was notably larger against one endpoint compared to the others, all three methods had similar power.ConclusionsAnalyzing multiple endpoints using a weighted permutation method can increase power while controlling the type I error rate in settings where outcomes share similar characteristics, like RSV outcomes. We developed an R package,PERMEATE, to guide selection of the most appropriate method for analyzing multiple endpoints in clinical trials.
Automatic quality control of single-cell and single-nucleus RNA-seq using valiDrops
Authors: Kavaliauskaite Gabija , Madsen Jesper Grud Skat 
Published: February 2023

AbstractSingle-cell and single-nucleus RNA-sequencing (sxRNA-seq) measures gene expression in individual cells or nuclei, which enables unbiased characterization of cell types and states in tissues. However, the isolation of cells or nuclei for sxRNA-seq can introduce artifacts, such as cell damage and transcript leakage. This can distort biological signals and introduce contamination from debris. Thus, the identification of barcodes con-taining high-quality cells or nuclei is a critical analytical step in the processing of sxRNA-seq data. Here, we present valiDrops, which is a novel data-adaptive method to identify high-quality barcodes and flag dead cells. In valiDrops, barcodes are initially filtered using data-adaptive thresholding on community-standard quality metrics and subsequently, valiDrops uses a novel clustering-based approach to identify barcodes with biological distinct signals. We benchmark valiDrops and existing methods and find that the biological signals from cell types and states are more distinct, easier to separate and more consistent after filtering by valiDrops. Finally, we show that valiDrops can be used to predict and flag dead cells with high accuracy. This novel classifier can further improve data quality or be used to identify dead cells to interrogate the biology of cell death. Thus, valiDrops is an effective and easy-to-use method to remove barcodes associated with low quality cells or nuclei from sxRNA-seq datasets, thereby improving data quality and biological interpretation. Our method is openly available as an R package atwww.github.com/madsen-lab/valiDrops.
Phantom touch illusion, an unexpected phenomenological effect of tactile gating in the absence of tactile stimulation
Authors: Pilacinski Artur , Metzler Marita , Klaes Christian 
Published: February 2023

AbstractWe report the presence of a tingling sensation perceived during self touch without physical stimulation. We used immersive virtual reality scenarios in which subjects touched their body using a virtual object. This touch resulted in a tingling sensation corresponding to the location touched on the virtual body. We called it “phantom touch illusion” (PTI). Interestingly the illusion was also present when subjects touched invisible (inferred) parts of their limb. We reason that this PTI results from tactile gating process during self-touch. The reported PTI when touching invisible body parts indicates that tactile gating is not exclusively based on vision, but rather on multi-sensory, top-down input involving body schema. This finding shows that representations of own body are defined top-down, beyond the available sensory information.
Rigosertib promotes anti-tumor immunity via autophagic degradation of PD-L1 in colorectal cancer cells
Authors: Zhou Xinyi , Fu Dongliang , Yang Hang , Le Chenqin , Lu Yier , Wei Jingsun , Tang Yang , Zhang Jiawei , Yuan Ying , Ding Kefeng , Xiao Qian 
Published: February 2023

AbstractRigosertib (RGS) is a benzyl styryl sulfone which exhibits impressive cytotoxicity in cancer cells. However, its modulating effect on tumor immune microenvironment remains elusive. In our experiments, compared with immunodeficient mouse model, increased tumor growth arrest and robust anti-tumor immunity were observed in RGS-treated colorectal cancer (CRC) xenograft tumors in immunocompetent mice.Intriguingly, RGS markedly down-regulated programmed cell death ligand 1 (PD-L1) expression in both vivo and in vitro. Meanwhile, RGS increased autophagic vacuole number in CRC cells as seen by transmission electron microscopy and immunofluorescence. Moreover, increased LC3-II level and tandem- mRFP- GFP- LC3 labeled vacuole accumulation demonstrated RGS-induced autophagic flux.Mechanistically, it is the activation of AMP-activated protein kinase-UNC-51-like kinase 1 (AMPK-ULK1) axis, rather than the canonical mTOR signaling pathway, that plays a pivotal role in RGS-induced autophagy. AMPK-ULK1 dependent autophagy inhibition, by either short interfering RNA or chemical inhibitors, blocked RGS-induced PD-L1 degradation. Finally, RGS exhibited synergistic anti-tumor activity with cytotoxic T-lymphocyte-associated protein 4 monoclonal antibody in the CRC xenograft model. Furthermore, apart from the immunomodulatory effect, we also confirmed the direct cytotoxicity of RGS in inducing mitochondria-related apoptosis. Altogether, considering its PD-L1 inhibitory and cytotoxic effects, RGS could be a promising drug for CRC therapy.
The dual role of the angiosperm radiation on insect diversification
Authors: Peris David , Condamine Fabien L. 
Published: February 2023

AbstractMost of the animal pollination is realized by insects, interactions between them and flowering plants have been hypothesized to be important drivers of diversification. Yet, there is weak support for coevolutionary diversification in plant–pollinator interactions. Macroevolutionary studies on insect and plant diversities support the hypothesis that angiosperms evolved after an insect diversity peak in the Early Cretaceous, suggesting that gymnosperm pollinators may have been accessible for angiosperms when they evolved. We examined fossil and phylogenetic evidence documenting this hypothesis and provide new clues on the impact of angiosperm radiation on insect diversification. Using the family-level fossil record of insects and a Bayesian process-based approach, we estimated diversification rates and the role of six different variables on insect macroevolutionary history. We found that, among the six tested variables, angiosperms had a dual role that has changed through time with an attenuation of insect extinction in the Cretaceous and a driver of insect origination in the Cenozoic. However, increasing insect diversity, spore plants and global temperature also showed strong positive correlation with both origination and extinction rates of insects, suggesting that different drivers had important effect on insect evolution, not just angiosperms, which would deserve further studies.
Coordination between endoderm progression and gastruloid elongation controls endodermal morphotype choice
Authors: Farag Naama , Schiff Chen , Nachman Iftach 
Published: February 2023

AbstractEmbryos mostly follow a single morphogenetic trajectory, where variability is largely quantitative with no qualitative differences. This robustness stands in contrast to in-vitro embryo-like models, which, like most organoids, display a high degree of variability. What makes embryonic morphogenesis so robust is unclear.We use the gastruloid model to study the morphogenetic progression of definitive endoderm (DE) and its divergence. We first catalog the different morphologies and characterize their statistics. We then learn predictive models for the lineage morphotype based on earlier expression and morphology measurements. Finally, we analyze these models to identify key drivers of morphotype variability, and devise personalized (gastruloid-specific) as well as global interventions that will lower this variability and steer morphotype choice. In the process we identify two types of coordination that are lacking in the in-vitro model but are required for robust gut tube formation.We expect the insights obtained here will improve the quality and usability of 3D embryo-like models, chart a methodology extendable to other organoids for controlling variability, and will also shed light on the factors that provide the embryo its morphogenetic robustness.
Wnt activity reveals context-specific genetic effects on gene regulation in neural progenitors
Authors: Matoba Nana , Le Brandon D , Valone Jordan M , Wolter Justin M , Mory Jessica , Liang Dan , Aygün Nil , Broadaway K Alaine , Bond Marielle L , Mohlke Karen L , Zylka Mark J , Love Michael I , Stein Jason L 
Published: February 2023

AbstractGene regulatory effects in bulk-post mortem brain tissues are undetected at many non-coding brain trait-associated loci. We hypothesized that context-specific genetic variant function during stimulation of a developmental signaling pathway would explain additional regulatory mechanisms. We measured chromatin accessibility and gene expression following activation of the canonical Wnt pathway in primary human neural progenitors from 82 donors. TCF/LEF motifs, brain structure-, and neuropsychiatric disorder-associated variants were enriched within Wnt-responsive regulatory elements (REs). Genetically influenced REs were enriched in genomic regions under positive selection along the human lineage. Stimulation of the Wnt pathway increased the detection of genetically influenced REs/genes by 66.2%/52.7%, and led to the identification of 397 REs primed for effects on gene expression. Context-specific molecular quantitative trait loci increased brain-trait colocalizations by up to 70%, suggesting that genetic variant effects during early neurodevelopmental patterning lead to differences in adult brain and behavioral traits.
IQGAP2 regulates blood-brain barrier immune dynamics
Authors: Katdare Ketaki A. , Kjar Andrew , O’Brown Natasha M. , Neal Emma H. , Sorets Alexander G. , Shostak Alena , Romero-Fernandez Wilber , Kwiatkowski Alexander J. , Mlouk Kate , Kim Hyosung , Cowell Rebecca P. , Schwensen Katrina R. , Horner Kensley B. , Wilson John T. , Schrag Matthew S. , Megason Sean G. , Lippmann Ethan S. 
Published: February 2023

AbstractBrain endothelial cells (BECs) play an important role in maintaining central nervous system (CNS) homeostasis through blood-brain barrier (BBB) functions. BECs express low baseline levels of adhesion receptors, which limits entry of leukocytes. However, the molecular mediators governing this phenotype remain mostly unclear. Here, we explored how infiltration of immune cells across the BBB is influenced by the scaffold protein IQ motif containing GTPase activating protein 2 (IQGAP2). In mice and zebrafish, we demonstrate that loss of Iqgap2 increases infiltration of peripheral leukocytes into the CNS under homeostatic and inflammatory conditions. Using single-cell RNA sequencing and immunohistology, we further show that BECs from mice lacking Iqgap2 exhibit a profound inflammatory signature, including extensive upregulation of adhesion receptors and antigen-processing machinery. Human tissue analyses also reveal that Alzheimer’s disease is associated with reduced hippocampal IQGAP2. Overall, our results implicate IQGAP2 as an essential regulator of BBB immune privilege and immune cell entry into the CNS.
Diminishing neuronal acidification by channelrhodopsins with low proton conduction
Authors: Hayward Rebecca Frank , Brooks F. Phil , Yang Shang , Gao Shiqiang , Cohen Adam E 
Published: February 2023

AbstractMany channelrhodopsins are permeable to protons. We found that in neurons, activation of a high-current channelrhodopsin, CheRiff, led to significant acidification, with faster acidification in the dendrites than in the soma. Experiments with patterned optogenetic stimulation in monolayers of HEK cells established that the acidification was due to proton transport through the opsin, rather than through other voltage-dependent channels. We identified and characterized two opsins which showed large photocurrents, but small proton permeability, PsCatCh2.0 and ChR2-3M. PsCatCh2.0 showed excellent response kinetics and was also spectrally compatible with simultaneous voltage imaging with QuasAr6a. Stimulation-evoked acidification is a possible source of disruptions to cell health in scientific and prospective therapeutic applications of optogenetics. Channelrhodopsins with low proton permeability are a promising strategy for avoiding these problems.Statement of SignificanceAcidification is an undesirable artifact of optogenetic stimulation. Low proton-permeability opsins minimize this artifact while still allowing robust optogenetic control.
Artificial physics engine for real-time inverse dynamics of arm and hand movement
Authors: Manukian Mykhailo , Bahdasariants Serhii , Yakovenko Sergiy 
Published: February 2023

AbstractSimulating human body dynamics requires detailed and accurate mathematical models. When solved inversely, these models provide a comprehensive description of force generation that evaluates subject morphology and can be applied to control real-time assistive technology, for example, orthosis or muscle/nerve stimulation. Yet, model complexity hinders the speed of its computations and may require approximations as a mitigation strategy. Here, we use machine learning algorithms to provide a method for accurate physics simulations and subject-specific parameterization. Several types of artificial neural networks (ANNs) with varied architecture were tasked to generate the inverse dynamic transformation of realistic arm and hand movement (23 degrees of freedom). Using a physical model to generate the training and testing sets for the limb workspace, we developed the ANN transformations with low torque errors (less than 0.1 Nm). Multiple ANN implementations using kinematic sequences solved accurately and robustly the high-dimensional kinematic Jacobian and inverse dynamics of arm and hand. These results provide further support for the use of ANN architectures that use temporal trajectories of time-delayed values to make accurate predictions of limb dynamics.
Shared evolutionary path in social microbiomes
Authors: Frazão Nelson , Gordo Isabel 
Published: February 2023

AbstractSocial networks can influence the ecology of gut bacteria, shaping the species composition of the gut microbiome in humans and other animals. Gut commensals evolve and can adapt at a rapid pace when colonizing healthy hosts. Here, we aimed at assessing the impact of host-to-host bacterial transmission onEscherichia colievolution in the mammalian gut. Using anin vivoexperimental evolution approach in mice, we found a transmission rate of 7% (±3% 2SE) ofE. colicells per day between hosts inhabiting the same household. Consistent with the predictions of a simple population genetics model of mutation-selection-migration, the level of shared events resulting from within host evolution is greatly enhanced in co-housed mice, showing that hosts undergoing the same diet and habit are not only expected to have similar microbiome species compositions but also similar microbiome evolutionary dynamics. Furthermore, we estimated the rate of mutation accumulation ofE. colito be 2.9×10−3(±5×10−42SE) mutations/genome/generation, irrespective of the social context of the regime. Our results reveal the impact of bacterial migration across hosts in shaping the adaptive evolution of new strains colonizing gut microbiomes.
POLCAM: Instant molecular orientation microscopy for the life sciences
Authors: Bruggeman Ezra , Zhang Oumeng , Needham Lisa-Maria , Körbel Markus , Daly Sam , Cheetham Matthew , Peters Ruby , Wu Tingting , Klymchenko Andrey S. , Davis Simon J. , Paluch Ewa K. , Klenerman David , Lew Matthew D. , O’Holleran Kevin , Lee Steven F. 
Published: February 2023

AbstractCurrent methods for single-molecule orientation localization microscopy (SMOLM) require optical setups and algorithms that can be prohibitively slow and complex, limiting the widespread adoption for biological applications. We present POLCAM, a simplified SMOLM method based on polarized detection using a polarization camera, that can be easily implemented on any wide-field fluorescence microscope. To make polarization cameras compatible with single-molecule detection, we developed theory to minimize field of view errors, used simulations to optimize experimental design, and developed a fast algorithm based on Stokes parameter estimation which can operate over 1000 fold faster than the state of the art, enabling near instant determination of molecular anisotropy. To aid in the adoption of POLCAM, we developed open-source image analysis software, and a website detailing hardware installation and software use. To illustrate the potential of POLCAM in the life sciences, we applied our method to study alpha-synuclein fibrils, the actin cytoskeleton of mammalian cells, fibroblast-like cells and the plasma membrane of live human T cells.
How do different functional groups of crop perform in temperate silvoarable agroforestry systems? A case study
Authors: Vaccaro Christina , Six Johan , Schöb Christian 
Published: February 2023

AbstractAgroforestry systems provide a number of ecosystem services and are frequently considered as a promising diversification strategy for more sustainable and climate resilient primary production. Still, less than 1% of the agricultural land in the European Union is silvoarable agroforestry. Most agroforestry field trials compare one crop type with a control in open field with no additional environmental treatments such as nutrient and water availability, thereby limiting our understanding of the ecological processes underlying the potential benefits of agroforestry for food production. The present experimental study addresses three factors (shade, fertilisation, irrigation) on three functionally different crop species (field bean, summer barley, summer rapeseed) and a C4-grass (Echinochloa crus-galli) in a Swiss agroforestry system. The objective of this study was to assess if and how crop performance (physiological traits, yield) between functional groups varies and if and how shade-induced crop yield reductions diverge between treatment combinations, aiming to provide general functional crop species and management recommendations as a guideline for a successful agroforestry practice in temperate Europe. Summer barley (−44%) and field bean (−38%) showed significant yield declines, similar to summer rapeseed with a significant biomass decline (−35%). Shade significantly increased the occurrence of lodging in barley. Rapeseed in particular performed better when fertilised (+40% biomass). Our results enable to estimate the range of potential yield losses in the competitive zone near mature trees for functionally different crop types and serve as a decision-support for species selection in temperate European agroforestry systems.