bluuebunny/crossref_metadata_2025_split huggingface dataset:
Runx1 regulates critical factors that control uterine angiogenesis and trophoblast differentiation during placental development
Authors: Kannan Athilakshmi , Beal Jacob R. , Neff Alison M. , Bagchi Milan K. , Bagchi Indrani C. 
Published: March 2023

ABSTRACTDuring early pregnancy in humans and rodents, uterine stromal cells undergo a remarkable differentiation to form the decidua, a transient maternal tissue that supports the growing fetus. It is important to understand the key decidual pathways that orchestrate the proper development of the placenta, a key structure at the maternal-fetal interface. We discovered that ablation of expression of the transcription factor Runx1 in decidual stromal cells in a conditionalRunx1-null mouse model (Runx1d/d) causes fetal lethality during placentation. Further phenotypic analysis revealed that uteri of pregnantRunx1d/dmice exhibited severely compromised decidual angiogenesis, and a lack of trophoblast differentiation and migration, resulting in impaired spiral artery remodeling. Gene expression profiling using uteri fromRunx1d/dand control mice revealed that Runx1 directly controls the decidual expression of the gap junction protein connexin 43 (also known as GJA1), which was previously shown to be essential for decidual angiogenesis. Our study also revealed a critical role of Runx1 in controlling insulin-like growth factor (IGF) signaling at the maternal-fetal interface. While Runx1-deficiency drastically reduced the production of IGF2 by the decidual cells, we observed concurrent elevated expression of the IGF-binding protein 4 (IGFBP4), which regulates the bioavailability of IGFs thereby controlling trophoblast differentiation. We posit that dysregulated expression of GJA1, IGF2, and IGFBP4 inRunx1d/ddecidua contributes to the observed defects in uterine angiogenesis, trophoblast differentiation, and vascular remodeling. This study therefore provides unique insights into key maternal pathways that control the early phases of maternal-fetal interactions within a critical window during placental development.SignificanceA clear understanding of the maternal pathways that ensure coordination of uterine differentiation and angiogenesis with embryonic growth during the critical early stages of placenta formation still eludes us. The present study reveals that the transcription factor Runx1 controls a set of molecular, cellular, and integrative mechanisms that mediate maternal adaptive responses controlling uterine angiogenesis, trophoblast differentiation, and resultant uterine vascular remodeling, which are essential steps during placenta development.
Retrospective transcriptome analyses identifyLINC01013as an activation marker in human dermal fibroblasts
Authors: Dolivo David M. , Rodrigues Adrian E. , Galiano Robert D. , Mustoe Thomas A. , Hong Seok Jong 
Published: March 2023

AbstractStudy of fibroblast biology, including the process of fibroblast activation, is critical to our understanding of wound healing, tissue fibrosis, and cancer. However, the rapid adoption of next-generation sequencing technologies, particularly single-cell RNA-seq and spatial transcriptomics, has revealed that fibroblast heterogeneity of both healthy and pathological tissues is more complicated than we currently understand. Therefore, a better understanding of molecular players that are not only indicative of but also that contribute to fibroblast activation is critical to piecing together the complete picture and to informing therapeutic strategies to combat associated pathologies. Here we focus on a long-noncoding RNA,LINC01013, recently implicated in pathological activation of cardiac fibroblasts and valvular interstitial cell. We analyze several sets of publicly available human transcriptomic data with the aim of determining whetherLINC01013correlates with fibroblast activation state, and whether compounds that affect fibroblast activation also modulate expression ofLINC01013. We find that, in numerous independent datasets of healthy and diseased human fibroblasts,LINC01013expression is associated with fibroblast activation. We also describe that, even in datasets comprised of small sample sizes, statistically significant correlations exist between expression ofLINC01013and expression of fibroblast activation markersACTA2andCCN2. This finding, while preliminary, suggests that changes inLINC01013expression may be an indicator of changes in fibroblast activation state, and thatLINC01013might functionally contribute to fibroblast activation, lending potential rationale for greater exploration of this lncRNA in the context of tissue fibrosis or tumor stroma.
Effects on wrong-patient errors by limiting access to concurrently open ERH charts: A preliminary systematic mapping and synthesis review
Authors: Myronuk Lonn D. S. 
Published: March 2023

AbstractBackgroundSeveral recent outcome studies have been published looking at the effects of restricting electronic health record (EHR) user interfaces to limit the number of concurrently accessible patient records. Strong recommendations have been in place for several years to have user interfaces constrained to only display one patient chart at a time in order to reduce the risk of data (documentation, orders) being entered on the wrong patient (Joint Commission, 2015; ONC, 2016). This recommendation was made based on expert opinion rather than objective information, raising the question whether the accumulating evidence supports continued implementation of such chart access restrictions.ObjectivesThis work reports a systematic mapping and synthesis review addressing research questions, “What is the evidence that restricting the number of concurrently open records reduces errors? (RQ1), “How effective is restriction of concurrently open charts at reducing wrong-patient errors? (RQ2), and “What additional inquiry is needed to make evidence-based policy decisions about restricting concurrent chart access? (RQ3).MethodsA systematic search of CINAHL, PubMed, and Web of Science databases was performed with full search string specification to retrieve a result set that is the conjunction of result sets for concepts ofEHR, concurrently open charts, andmedical error. Of 407 studies identified and screened, five were eligible for inclusion in the qualitative synthesis review, and three were amenable to data extraction and pooled effect size calculation.ResultsNone of the studies included for review found evidence of statistically significant change in wrong-patient error rates associated with implementing restriction in the number of patient records allowed to be open concurrently in the EHR. The combined OR for the pooled studies was 1.02 (95% CI 0.90 – 1.15) with low estimates for inter-study heterogeneity and no indication of publication bias.ConclusionThere is no evidence that restricting the number of concurrently open records reduces errors (RQ1). It is not possible to definitively answer RQ2, but the magnitude of any yet to be detected beneficial effect that might be lost with lifting of chart access restriction can be no greater than an absolute risk increase of 33 errors per 100,000 ordering sessions. While it has been claimed that restricting the number of concurrently open EHR records is necessary for patient safety, the present review demonstrates that it is insufficient to attain a measurable improvement in error rates. Additional investigation of the usability and human factors aspects of EHR configuration decisions as well as knowledge of the impacts on clinical workflows will be necessary to provide policymakers, operational leaders, and practitioners with insight into the nature of the threats and opportunities with respect to safety, as well as the strengths and weaknesses of potential interventions.
Immune responses and disease biomarker long-term changes following COVID-19 mRNA vaccination in a cohort of rheumatic disease patients
Authors: An Zesheng , Zhou Xian , Li Yanfeng , Jaquith Jane , McCarthy-Fruin Kathleen , Sletten Jennifer , Warrington Kenneth J. , Weyand Cornelia , Crowson Cynthia S. , Chumsri Saranya , Knutson Keith L. , Figueroa-Parra Gabriel , Sanchez-Rodriguez Alain , Thanarajasingam Uma , Duarte-García Alí , Zeng Hu 
Published: March 2023

ABSTRACTObjectiveTo evaluate seroreactivity and disease biomarkers after 2 or 3 doses of COVID-19 mRNA vaccines in a cohort of patients with rheumatic diseases.MethodsWe collected biological samples longitudinally before and after 2-3 doses of COVID-19 mRNA vaccines from a cohort of patients with systemic lupus erythematosus (SLE), psoriatic arthritis, Sjogren’s syndrome, ankylosing spondylitis, and inflammatory myositis. Anti-SARS-CoV-2 spike IgG and IgA and anti-dsDNA concentration were measured by ELISA. A surrogate neutralization assay was utilized to measure antibody neutralization ability. Lupus disease activity was measured by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Expression of type I interferon signature was measured by real-time PCR. The frequency of extrafollicular double negative 2 (DN2) B cells was measured by flow cytometry.ResultsMost of the patients generated high SARS-CoV-2 spike-specific neutralizing antibodies comparable to those in healthy controls after 2 doses of mRNA vaccines. The antibody level declined over time but recovered after the third dose of the vaccine. Rituximab treatment substantially reduced antibody level and neutralization ability. Among SLE patients, no consistent increase in SLEDAI scores was observed post-vaccination. The changes in anti-dsDNA antibody concentration and expression of type I IFN signature genes were highly variable but did not show consistent or significant increases. Frequency of DN2 B cells remained largely stable.ConclusionRheumatic disease patients without rituximab treatment have robust antibody responses toward COVID-19 mRNA vaccination. Disease activity and disease-associated biomarkers remain largely stable over 3 doses of vaccines, suggesting that COVID-19 mRNA vaccines may not exacerbate rheumatic diseases.KEY MESSAGESPatients with rheumatic diseases mount robust humoral immunity towards 3 doses of COVID-19 mRNA vaccines.Disease activity and biomarkers remain stable following 3 doses of COVID-19 mRNA vaccines.
Circulating immune cell populations at rest and in response to acute endurance exercise in young adults with cerebral palsy
Authors: Kruse Annika , Imery Ian , Corell Linnéa , Hjalmarsson Emma , Fernandez-Gonzalo Rodrigo , von Walden Ferdinand , Reitzner Stefan M. 
Published: March 2023

AbstractAimLow physical activity alters immune function and increases the risk of developing chronic inflammation. This cross-sectional study aimed at determining the immune status and function in young adults with cerebral palsy (CP) in comparison to typically developing (TD) individuals.MethodBlood samples from 12 individuals with CP and 17 TD were collected before, immediately after, and one hour following 45 minutes of Frame Running or running, respectively. Independent t-tests were used to compare heart rate, level of exertion, and baseline cell proportions between groups. Mixed model ANOVA was utilized to investigate immune cell responses to exercise across groups.ResultsBaseline levels of TCRγδ+ T-cells were significantly higher in the individuals with CP. Several cell populations showed significant changes after exercise in both CP and TD groups. CD8+ T-cells were only significantly elevated immediately after exercise in the TD participants. Individuals with CP exhibited significantly lower heart rates, despite similar ratings of perceived exertion.InterpretationElevated baseline TCRγδ+ T-cells may indicate low-grade inflammation in adults with CP. Although most of the cell populations showed typical responses to endurance exercise, the absence of response in CD8+ T-cells in individuals with CP may indicate the need for higher intensity during exercise.What this paper addsThis is the first study addressing immune cells in adults with CPTCRγδ+ T-cell baseline levels are elevated in adults with CPThe CD8+ T-cell response to exercise was blunted in adults with CPExercise intensity is decisive for CD8+ T-cell responses in individuals with CP
Single-cell transcriptomics reveals that glial cells integrate homeostatic and circadian processes to drive sleep-wake cycles
Authors: Dopp Joana , Ortega Antonio , Davie Kristofer , Poovathingal Suresh , Baz El-Sayed , Liu Sha 
Published: March 2023

AbstractThe sleep-wake cycle is determined by circadian and sleep homeostatic processes. However, the molecular impact of these processes and their interaction in different brain cell populations remain unknown. To fill this gap, we profiled the single-cell transcriptome of adultDrosophilabrains across the sleep-wake cycle and four circadian times. We show cell type-specific transcriptomic changes with glia displaying the largest variation. Glia are also among the few cell types whose gene expression correlates with both sleep homeostat and circadian clock. The sleep-wake cycle and sleep drive level affect expression of clock gene regulators in glia, while diminishing the circadian clock specifically in glia impairs homeostatic sleep rebound after sleep deprivation. These findings reveal a comprehensive view of the effects of sleep homeostatic and circadian processes on distinct cell types in an entire animal brain and reveal glia as an interaction site of these two processes to determine sleep-wake dynamics.
Schrödinger’s Cat in Simulations in Genome-wide Association Studies
Authors: Ozkaraca Mustafa Ismail , Tenesa Albert 
Published: March 2023

AbstractSimulations are essential components for testing methods or assumptions in genome-wide association studies (GWAS). We show through theory and examples that markers can be both causal and non-causal simultaneously, resulting in a paradox, had simulation not being run properly. We developed a software (ParaPheSim – a paradoxical phenotype simulator) that allows users to create different traits whose genetic correlation is exactly 1 and yet they have no genetic overlap.
Group AStreptococcusstrains causing meningitis without distinct invasive phenotype
Authors: Marquardt Laura , Andreoni Federica , Boumasmoud Mathilde , Schweizer Tiziano A. , Heuberger Dorothea M. , Parietti Elena , Hertegonne Sanne , Epprecht Jana , Mattle Dario , Raez Anna K. , Marques-Maggio Ewerton , Schuepbach Reto A. , Hasse Barbara , Mairpady-Shambat Srikanth , Brugger Silvio D. , Zinkernagel Annelies S. 
Published: March 2023

AbstractGroup A streptococcal (GAS, akaStreptococcus pyogenes) meningitis is a fulminant disease associated with high morbidity and mortality. To elucidate the mechanisms underlying the invasiveness of GAS in meningitis, we compared GAS isolates derived from five cases of meningitis, to otitis and colonizing isolates. We did not observe differences in adherence to and invasion of human brain microvascular endothelial cells, virulence factors activity or barrier disruption. Whole genome sequencing did not reveal particular invasiveness traits. Most patients previously suffered from otitis media suggesting that meningitis likely resulted from a continuous spread of the infection rather than being attributable to changes in pathogen’s virulence.
Re-evaluating the nuclear staining on pathological sections in Alzheimer’s disease
Authors: Fu Hualin , Li Jilong , Zhang Chunlei , Du Peng , Gao Guo , Ge Qiqi , Guan Xinping , Cui Daxiang 
Published: March 2023

AbstractA paper recently published on Nature Neuroscience, asserting that lysosome leakage induces neuronal cell death and the formation of senile plaques in Alzheimer’s disease. The study believed that flower-like perikaryal rosettes formed by packed autophagic vacuoles around central nuclei, termed “PANTHOS” neurons, are responsible for the senile plaque formation. However, all of the nuclei staining in this paper based on images in the blue fluorescence channel. We did detailed studies on the senile plaque blue autofluorescence and found that senile plaque blue autofluorescence could be easily mistaken as nuclear staining. The blue “nuclear” staining in this paper is probably inaccurate since it was not verified in red or green fluorescence channels and their “nuclei”-related data might be mis-interpreted.
A domain-agnostic MR reconstruction framework using a randomly weighted neural network
Authors: Pal Arghya , Ning Lipeng , Rathi Yogesh 
Published: March 2023

PurposeTo design a randomly-weighted neural network that performs domain-agnostic MR image reconstruction from undersampled k-space data without the need for ground truth or extensive in-vivo training datasets. The network performance must be similar to the current state-of-the-art algorithms that require large training datasets.MethodsWe propose a Weight Agnostic randomly weighted Network method for MRI reconstruction (termed WAN-MRI) which does not require updating the weights of the neural network but rather chooses the most appropriate connections of the network to reconstruct the data from undersampled k-space measurements. The network architecture has three components, i.e. (1) Dimensionality Reduction Layers comprising of 3d convolutions, ReLu, and batch norm; (2) Reshaping Layer is Fully Connected layer; and (3) Upsampling Layers that resembles the ConvDecoder architecture. The proposed methodology is validated on fastMRI knee and brain datasets.ResultsThe proposed method provides a significant boost in performance for structural similarity index measure (SSIM) and root mean squared error (RMSE) scores on fastMRI knee and brain datasets at an undersampling factor of R=4 and R=8 while trained on fractal and natural images, and fine-tuned with only 20 samples from the fastMRI training k-space dataset. Qualitatively, we see that classical methods such as GRAPPA and SENSE fail to capture the subtle details that are clinically relevant. We either outperform or show comparable performance with several existing deep learning techniques (that require extensive training) like GrappaNET, VariationNET, J-MoDL, and RAKI.ConclusionThe proposed algorithm (WAN-MRI) is agnostic to reconstructing images of different body organs or MRI modalities and provides excellent scores in terms of SSIM, PSNR, and RMSE metrics and generalizes better to out-of-distribution examples. The methodology does not require ground truth data and can be trained using very few undersampled multi-coil k-space training samples.
Atlas ofPlasmodium falciparumintraerythrocytic development using expansion microscopy
Authors: Liffner Benjamin , Cepeda Diaz Ana Karla , Blauwkamp James , Anaguano David , Frölich Sonja , Muralidharan Vasant , Wilson Danny W. , Dvorin Jeffrey , Absalon Sabrina 
Published: March 2023

ABSTRACTApicomplexan parasites exhibit tremendous diversity in much of their fundamental cell biology, but study of these organisms using light microscopy is often hindered by their small size. Ultrastructural expansion microscopy (U-ExM) is a microscopy preparation method that physically expands the sample ∼4.5x. Here, we apply U-ExM to the human malaria parasitePlasmodium falciparumduring the asexual blood stage of its lifecycle to understand how this parasite is organized in three-dimensions. Using a combination of dye-conjugated reagents and immunostaining, we have catalogued 13 differentP. falciparumstructures or organelles across the intraerythrocytic development of this parasite and made multiple observations about fundamental parasite cell biology. We describe that the outer centriolar plaque and its associated proteins anchor the nucleus to the parasite plasma membrane during mitosis. Furthermore, the rhoptries, Golgi, basal complex, and inner membrane complex, which form around this anchoring site while nuclei are still dividing, are concurrently segregated and maintain an association to the outer centriolar plaque until the start of segmentation. We also show that the mitochondrion and apicoplast undergo sequential fission events while maintaining an association with the outer centriolar plaque during cytokinesis. Collectively, this study represents the most detailed ultrastructural analysis ofP. falciparumduring its intraerythrocytic development to date, and sheds light on multiple poorly understood aspects of its organelle biogenesis and fundamental cell biology.IMPACT STATEMENTUsing ultrastructure-expansion microscopy we explore the fundamental cell biology of malaria parasites, providing new insights into processes including establishment of cell polarity and organelle fission.
Latent transcriptional programs reveal histology-encoded tumor features spanning tissue origins
Authors: Hieromnimon Hanna M. , Dolezal James , Doytcheva Kristina , Howard Frederick M. , Kochanny Sara , Zhang Zhenyu , Grossman Robert L. , Tanager Kevin , Wang Cindy , Kather Jakob Nikolas , Izumchenko Evgeny , Cipriani Nicole A , Fertig Elana J. , Pearson Alexander T , Riesenfeld Samantha J 
Published: March 2023

AbstractPrecision medicine in cancer treatment depends on deciphering tumor phenotypes to reveal the underlying biological processes. Molecular profiles, including transcriptomics, provide an information-rich tumor view, but their high-dimensional features and assay costs can be prohibitive for clinical translation at scale. Recent studies have suggested jointly leveraging histology and genomics as a strategy for developing practical clinical biomarkers. Here, we use machine learning techniques to identifyde novolatent transcriptional processes in squamous cell carcinomas (SCCs) and to accurately predict their activity levels directly from tumor histology images. In contrast to analyses focusing on pre-specified, individual genes or sample groups, our latent space analysis reveals sets of genes associated with both histologically detectable features and clinically relevant processes, including immune response, collagen remodeling, and fibrosis. The results demonstrate an approach for discovering clinically interpretable histological features that indicate complex, potentially treatment-informing biological processes.
Active dendrites enable robust spiking computations despite timing jitter
Authors: Burger Thomas SJ , Rule Michael E , O’Leary Timothy 
Published: March 2023

AbstractDendritic action potentials exhibit long plateaus of many tens of milliseconds, outliving axonal spikes by an order of magnitude. The computational role of these slow events seems at odds with the need to rapidly integrate and relay information throughout large nervous systems. We propose that the timescale of dendritic potentials allows for reliable integration of asynchronous inputs. We develop a physiologically grounded model in which the extended duration of dendritic spikes equips each dendrite with a resettable memory of incoming signals. This provides a tractable model for capturing dendritic nonlinearities observed in experiments and in more complex, detailed models. Using this model, we show that long-lived, nonlinear dendritic plateau potentials allow neurons to spike reliably when confronted with asynchronous input spikes. We demonstrate this model supports non-trivial computations in a network solving an association/discrimination task using sparse spiking that is subject to timing jitter. This demonstrates a computational role for the specific time-course of dendritic potentials in situations where decisions occur quickly, reliably, and with a low number of spikes. Our results provide empirically testable hypotheses for the role of dendritic action potentials in cortical function as well as a potential bio-inspired means of realising neuromorphic spiking computations in analog hardware.