bluuebunny/crossref_metadata_2025_split huggingface dataset:
The COVID-19 Community Research Partnership: Objectives, Study Design, Baseline Recruitment, and Retention
Authors:   The COVID-19 Community Research Partnership, Sanders John 
Published: February 2022

ABSTRACTThe COVID-19 Community Research Partnership (CCRP) is a multisite surveillance platform designed to characterize the epidemiology of the SARS-CoV-2 pandemic. This manuscript describes the CCRP study design and methodology. The CCRP includes two prospective cohorts, one with six health systems in the mid-Atlantic and southern United States, and the other with six health systems in North Carolina. With enrollment beginning April 2020, sites invited persons within their healthcare systems as well as community members to participate in daily surveillance for symptoms of COVID-like illnesses, testing and risk behaviors. Participants with electronic health records were also asked to volunteer data access. Subsets of participants, representative of the general population and including oversampling of populations of interest, were selected for repeated at home serology testing. By October 2021, 65,739 participants (62,261 adult and 3,478 pediatric) were enrolled with 89% providing syndromic data, 74% providing EHR data, and 70% participating in one of two serology sub-studies. An average of 62% of participants completed a daily survey at least once a week, and 55% of serology kits were returned. The CCRP provides rich regional epidemiologic data and opportunities to more fully characterize the risks and sequelae of SARS-CoV-2 infection.
Diurnal modulation of subthalamic beta oscillatory power in Parkinson’s disease patients during deep brain stimulation
Authors: van Rheede Joram J. , Feldmann Lucia K. , Busch Johannes L. , Fleming John E. , Mathiopoulou Varvara , Denison Timothy , Sharott Andrew , Kühn Andrea A. 
Published: February 2022

AbstractBackgroundBeta band activity in the subthalamic local field potential (LFP) is correlated with Parkinson’s disease (PD) symptom severity, and is the therapeutic target and feedback signal for adaptive deep brain stimulation (aDBS). While clinically relevant beta fluctuations in PD patients are well characterised on shorter timescales and in the clinic, it is not known how beta activity evolves around the diurnal cycle, outside a clinical setting.ObjectiveTo characterise diurnal fluctuations in beta amplitude in PD patients receiving continuous, high frequency DBS.MethodsWe obtained chronic recordings (34±13 days) of subthalamic beta power in PD patients implanted with the Percept DBS device during high-frequency DBS, and analysed its diurnal properties. To investigate the influence of non-frequency-specific effects and artifacts, we compared beta to contralateral theta amplitude and recorded LFPs during various movements.ResultsBeta power had strong 24-hour periodicity, and time of day explained 41±9% of the variance in all long-term beta power recordings (p<0.001 in all patients). For all patients, beta activity was high during the day and reduced at night. Beta activity was not fully explained by theta activity and could show independent diurnal modulation. Movement artifacts affected the recorded LFPs, influenced band power estimates, and could have contributed to diurnal patterns in some patients.ConclusionsDiurnal fluctuations in beta amplitude will need to be accommodated in aDBS to prevent suboptimal stimulation, particularly at night. Careful screening and/or mitigation of movement artifacts is needed to ensure that the signal is suitable for adaptive stimulation or neurophysiological investigation.
Epigenetic Memory of COVID-19 in Innate Immune Cells and Their Progenitors
Authors: Cheong Jin-Gyu , Ravishankar Arjun , Sharma Siddhartha , Parkhurst Christopher N. , Nehar-Belaid Djamel , Ma Sai , Paddock Lucinda , Fatou Benoit , Karakaslar Onur , Thibodeau Asa , Bale Michael J. , Kartha Vinay K. , Yee Jim K , Mays Minh Yen , Leyre Louise , de Paz Alexia Martinez , Daman Andrew W. , Mullett Sergio Alvarez , Robbins Lexi , LaFond Elyse , Weidman Karissa , Racine-Brzostek Sabrina , Yang He S. , Price David , Jones Brad , Schenck Edward J. , Kaner Robert J. , Chadburn Amy , Zhao Zhen , Steen Hanno , Pascual Virginia , Buenrostro Jason , Niec Rachel E. , Lief Lindsay , Ucar Duygu , Josefowicz Steven Z. 
Published: February 2022

AbstractSevere coronavirus disease 2019 (COVID-19) is characterized by systemic inflammation and can result in protracted symptoms. Robust systemic inflammation may trigger persistent changes in hematopoietic cells and innate immune memory through epigenetic mechanisms. We reveal that rare circulating hematopoietic stem and progenitor cells (HSPC), enriched from human blood, match the diversity of HSPC in bone marrow, enabling investigation of hematopoiesis and HSPC epigenomics. Following COVID-19, HSPC retain epigenomic alterations that are conveyed, through differentiation, to progeny innate immune cells. Epigenomic changes vary with disease severity, persist for months to a year, and are associated with increased myeloid cell differentiation and inflammatory or antiviral programs. Epigenetic reprogramming of HSPC may underly altered immune function following infection and be broadly relevant, especially for millions of COVID-19 survivors.One Sentence SummaryTranscriptomic and epigenomic analysis of blood reveal sustained changes in hematopoiesis and innate immunity after COVID-19.Graphical Abstract
Identification of Alkaloids and Related Intermediates of Dendrobium officinale by Solid-Phase Extraction Coupled with High-Performance Liquid Chromatography Tandem Mass Spectrometry
Authors: Song Cheng , Zhang Yunpeng , Manzoor Muhammad Aamir , Li Guohui 
Published: February 2022

AbstractJA signaling plays a pivotal role in plant stress responses and secondary metabolism. Many studies have demonstrated that jasmonates effectively induce the expressions of alkaloid biosynthesis genes in various plants, which rendered to the accumulation of alkaloid to counteract stresses. Despite the multiple roles of jasmonate (JA) in the regulation of plant growth and different stresses, less studied involved in the regulatory role of JA in D. officinale alkaloids. A strategy for the rapid identification of alkaloid and the intermediates of D. officinale was established based on a solid-phase extraction coupled with high-performance liquid chromatography tandem mass spectrometry method. By using SPE-HPLC-LTQ-Orbitrap method, the potential compounds were tentatively identified by aligning the accurate molecular weight with the METLIN and Dictionary of Natural Products databases. The chemical structures and main characteristic fragments of the potential compounds were further confirmed by retrieving the multistage mass spectra from the MassBank and METLIN databases.The Mass Frontier software was used to speculate the fragmentation pathway of the identified compounds. Seven alkaloids were separated and identified from D. officinale, which were mainly classified into five types (tropane alkaloids, tetrahydroisoquinoline alkaloids, quinolizidine alkaloids, piperidine alkaloids and spermidine alkaloids). Besides the alkaloids, forty-nine chemical substances, including guanidines, nucleotides, dipeptides, sphingolipids and nitrogen-containing glucosides, were concurrently identified. These findings gives the composition of chemicals currently found in D. officinale, which could provide the scientific method for the identification of alkaloids in other Dendrobium plants.
Engineering Defensin α-helix to produce high-affinity SARS-CoV-2 Spike protein binding ligands
Authors: Fernandes Leonardo Antônio , Gomes Anderson Albino , Magalhães Maria de Lourdes Borba , Ray Partha , da Silva Gustavo Felippe 
Published: February 2022

AbstractThe binding of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike protein to the Angiotensin-Converting Enzyme 2 (ACE2) receptor expressed on the host cells is a critical initial step for viral infection. This interaction is blocked through competitive inhibition by soluble ACE2 protein. Therefore, developing high-affinity and cost-effective ACE2 peptidomimetic ligands that disrupt this protein-protein interaction is a promising strategy for viral diagnostics and therapy. We employed human and plant defensins, a class of small and highly stable proteins, and engineered the amino acid residues on its conformationally constrained alpha-helices to mimic the critical residues on the ACE2 helix 1 that interacts with the Spike-protein. The engineered proteins were soluble and purified to homogeneity with high yield from a bacterial expression system. The proteins demonstrated exceptional thermostability, high-affinity binding to the Spike protein with dissociation constants in the low nanomolar range, and were used in a diagnostic assay that detected SARS-CoV-2 neutralizing antibodies. This work addresses the challenge of developing helical peptidomimetics by demonstrating that defensins provide promising scaffolds to engineer alpha-helices in a constrained form for designing high-affinity ligands.Broad audience statementThe engineered proteins developed in this study are cost-effective and highly stable reagents for SARS-CoV-2 detection. These features may allow large-scale and cost-effective production of diagnostic tests to assist COVID-19 diagnostic and prevention.
Remdesivir and GS-441524 retain antiviral activity against Delta, Omicron, and other emergent SARS-CoV-2 variants
Authors: Pitts Jared , Li Jiani , Perry Jason K. , Du Pont Venice , Riola Nicholas , Rodriguez Lauren , Lu Xianghan , Kurhade Chaitanya , Xie Xuping , Camus Gregory , Manhas Savrina , Martin Ross , Shi Pei-Yong , Cihlar Tomas , Porter Danielle P. , Mo Hongmei , Maiorova Evguenia , Bilello John P. 
Published: February 2022

AbstractGenetic variation of SARS-CoV-2 has resulted in the emergence and rapid spread of multiple variants throughout the pandemic, of which Omicron is currently the predominant variant circulating worldwide. SARS-CoV-2 variants of concern or interest (VOC/VOI) have evidence of increased viral transmission, disease severity, or decreased effectiveness of vaccines and neutralizing antibodies. Remdesivir (RDV, VEKLURY®) is a nucleoside analog prodrug and the first FDA-approved antiviral treatment of COVID-19. Here we present a comprehensive antiviral activity assessment of RDV and its parent nucleoside, GS-441524, against 10 current and former SARS-CoV-2 VOC/VOI clinical isolates by nucleoprotein ELISA and plaque reduction assay.Delta and Omicron variants remained susceptible to RDV and GS-441524, with EC50values 0.31 to 0.62-fold of those observed against the ancestral WA1 isolate. All other tested variants exhibited EC50values ranging from 0.15 to 2.3-fold of the observed EC50values against WA1. Analysis of nearly 6 million publicly available variant isolate sequences confirmed that Nsp12, the RNA-dependent RNA polymerase (RdRp) target of RDV and GS-441524, is highly conserved across variants with only 2 prevalent changes (P323L and G671S). Using recombinant viruses, both RDV and GS-441524 retained potency against all viruses containing frequent variant substitutions or their combination. Taken together, these results highlight the conserved nature of SARS-CoV-2 Nsp12 and provide evidence of sustained SARS-CoV-2 antiviral activity of RDV and GS-441524 across the tested variants. The observed pan-variant activity of RDV supports its continued use for the treatment of COVID-19 regardless of the SARS-CoV-2 variant.
High-intensity interval or circuit-based strength training effects on physical and cognitive functioning for community-dwelling older adults: A systematic review protocol
Authors: Morgan Ashley , Noguchi Kenneth S , Tang Ada , Heisz Jennifer , Thabane Lehana , Richardson Julie 
Published: February 2022

ABSTRACTBackgroundHigh-intensity interval or circuit-based strength training utilizes brief intense periods of strengthening exercises interspersed with rest/light activity or performed in a continuous circuit. The physical and cognitive effects of this time-efficient approach in community-dwelling older adults have not been systematically reviewed.ObjectivesTo determine the effects of high-intensity interval or circuit-based strength training interventions on physical and cognitive functioning for community-dwelling older adults, and the associated adherence, retention, and adverse event rates.MethodsSix databases will be searched from inception to November 2021; MEDLINE, EMBASE, CINAHL, AgeLine, SPORTDiscus, and Web of Science. To assess physical and/or cognitive functioning effects, randomized and quasi-randomized controlled trials (RCTs and Q-RCTs) of high-intensity interval or circuit-based strengthening interventions in community-dwelling older adults, utilizing any comparator, will be included. The above criteria will be extended to include non-randomized study designs to assess adherence, retention, and adverse events. All screening, data extraction and risk of bias will be assessed by two independent reviewers. Risk of bias will be assessed utilizing the Cochrane RoB 2 tool for randomized and ROBINS-I for non-randomized studies. Qualitative synthesis will be used to present information on adherence, retention, and adverse event rates. Qualitative and/or quantitative synthesis will be used to present physical and cognitive functioning effects depending on which method is deemed appropriate for the various outcomes.ConclusionThis systematic review will be the first to summarize the physical and/or cognitive effects, adherence, retention, and adverse events reported in high-intensity interval and circuit-based strengthening interventions for community-dwelling older adults.Systematic review registration numberCRD42021284010
Acoel single-cell atlas reveals expression dynamics and heterogeneity of a pluripotent stem cell population
Authors: Hulett Ryan E. , Kimura Julian O. , Bolaños D. Marcela , Luo Yi-Jyun , Ricci Lorenzo , Srivastava Mansi 
Published: February 2022

AbstractPluripotent adult stem cell populations underlie whole-body regeneration in many distantly related animal lineages. These collectively pluripotent populations of cells share some features across species, such as the expression of piwi and other germline-related genes. Studies of how these cells operate during regeneration are needed in diverse systems to determine how underlying cellular and molecular mechanisms of renewal and differentiation compare. Here, we sought to characterize stem cells and their dynamics in the acoel Hofstenia miamia, a highly regenerative marine worm with a piwi-expressing stem cell population called neoblasts. Transcriptome profiling at single cell resolution revealed cell types shared across postembryonic stages, including stem cells and differentiated cell types such as neural, epidermal, muscle, and digestive cells. Reconstruction of single-cell differentiation trajectories followed by functional studies confirmed that neoblasts are the source of differentiated cells and identified transcription factors needed for the formation of major cell types. Next, analysis of single-cell transcriptomes from regenerating worms showed that both differentiated cells and stem cells dynamically alter gene expression in response to amputation. Further analysis of the stem cells recovered subpopulations of neoblasts, each with specific transcriptional profiles suggesting that the majority of neoblasts are specialized to differentiated lineages, reflecting putatively lineage-primed progenitors. Notably, neoblast subsets in Hofstenia were identifiable consistently across postembryonic stages and also displayed differential expression dynamics in response to wounding. Altogether, these data suggest that whole-body regeneration is accomplished by the coordination of cells with distinct and dynamic transcriptomic profiles through time. Furthermore, the data generated here will enable the study of how this coordination is achieved, enhancing our understanding of pluripotent stem cells and their evolution across metazoans.
False-Positive IRESes from Hoxa9 and other genes resulting from errors in mammalian 5’ UTR annotations
Authors: Akirtava Christina , May Gemma E. , McManus C. Joel 
Published: February 2022

AbstractHyperconserved genomic sequences have great promise for understanding core biological processes. It has been recently proposed that scores of hyperconserved transcript leaders (hTLs) encode Internal Ribosome Entry Sites (IRESes) that drive cap-independent translation in part via interactions with ribosome expansion segments. However, the direct functional significance of such interactions has not yet been definitively demonstrated. We provide evidence that the putative IRESes previously reported in Hox gene hTLs are rarely included in transcript leaders. Instead, these regions function independently as transcriptional promoters. In addition, we find the proposed RNA structure of the putative Hoxa9 IRES is not conserved. Instead, sequences previously shown to be essential for putative IRES activity encode a hyperconserved transcription factor binding site (E-box) that contributes to its promoter activity by binding to the transcription factors USF1 and USF2. Similar E-box sequences enhance the promoter activities of other putative Hoxa gene IRESes. Moreover, we provide evidence that the vast majority of hTLs with putative IRES activity overlap transcriptional promoters, enhancers, and 3’ splice sites that are most likely responsible for their reported IRES activities. These results argue strongly against recently reported widespread IRES-like activities from hTLs and contradict proposed interactions between ribosomal expansion segment ES9S and putative IRESes. Furthermore, our work underscores the importance of accurate transcript annotations, controls in bicistronic reporter assays, and the power of synthesizing publicly available data from multiple sources.
Assessing Quantitative MRI Techniques using Multimodal Comparisons
Authors: Carter Francis , Anwander Alfred , Goucha Thomás , Adamson Helyne , Friederici Angela D. , Lutti Antoine , Gauthier Claudine J , Weiskopf Nikolaus , Bazin Pierre-Louis , Steele Christopher J 
Published: February 2022

AbstractThe study of brain structure and change in neuroscience is commonly conducted using macroscopic morphological measures of the brain such as regional volume or cortical thickness, providing little insight into the microstructure and physiology of the brain. In contrast, quantitative MRI allows the monitoring of microscopic brain change non-invasively in-vivo, and provides normative values for comparisons between tissues, regions, and individuals. To support the development and common use of qMRI for cognitive neuroscience, we analysed a set of qMRI metrics (R1, R2*, Magnetization Transfer saturation, Proton Density saturation, Fractional Anisotropy, Mean Diffusivity) in 101 healthy young adults. Here we provide a comprehensive descriptive analysis of these metrics and their linear relationships to each other in grey and white matter to develop a more complete understanding of the relationship to tissue microstructure. Furthermore, we provide evidence that combinations of metrics may uncover informative gradients across the brain by showing that lower variance components of PCA may be used to identify cortical gradients otherwise hidden within individual metrics. We discuss these results within the context of microstructural and physiological neuroscience research.
CD8 T Cell Memory Inflation is Driven by Latent CMV Infection of Lymphatic Endothelial Cells
Authors: Munks Michael W. , Rott Katherine , Nesterenko Pavlo A. , Smart Savannah M. , Williams Venasha , Tatum Angela , Xu George , Smith Tameka , Murray Susan E. , Hill Ann B. 
Published: February 2022

ABSTRACTCMV, a ubiquitous herpesvirus, elicits an extraordinarily large T cell response that is sustained or increases over time, a phenomenon termed ‘memory inflation.’ Remarkably, even latent, non-productive infection can drive memory inflation. Despite intense research on this phenomenon, the infected cell type(s) involved are unknown. To identify the responsible cell type(s), we designed a Cre-lox murine CMV (MCMV) system, where a spread-deficient (ΔgL) virus expresses recombinant SIINFEKL only in Cre+ host cells. We found that latent infection of endothelial cells (ECs), but not dendritic cells (DCs) or hepatocytes, was sufficient to drive CD8 T cell memory inflation. Infection of Lyve-1-Cre and Prox1-CreERT2 mice revealed that amongst EC subsets, infection of lymphatic ECs was sufficient. Genetic ablation of β2m on lymphatic ECs did not prevent inflation, suggesting another unidentified cell type can also present antigen to CD8 T cells during latency. This novel system definitively shows that antigen presentation by lymphatic ECs drives robust CD8 T cell memory inflation.SUMMARYActive T cell immunosurveillance during latent CMV infection results in T cell ‘memory inflation.’ A novel Cre-lox genetic system for cell-specific antigen expression reveals that lymphatic ECs, but not DCs or hepatocytes, can drive CD8 T cell memory inflation.
Targeting NAAA counters dopamine neuron loss and symptom progression in mouse models of Parkinson’s disease
Authors: Palese Francesca , Pontis Silvia , Realini Natalia , Torrens Alexa , Ahmed Faizy , Assogna Francesca , Pellicano Clelia , Bossù Paola , Spalletta Gianfranco , Green Kim , Piomelli Daniele 
Published: February 2022

ABSTRACTThe lysosomal cysteine hydrolase N-acylethanolamine acid amidase (NAAA) deactivates the lipidderived mediator palmitoylethanolamide (PEA), an endogenous PPAR-α agonist that is critically involved in the control of inflammation and nociception. In this study, we asked whether NAAA-regulated PEA signaling might contribute to the pathogenesis of Parkinson’s disease (PD), a neurodegenerative disorder characterized by progressive loss of nigrostriatal dopamine neurons. Analyses of postmortem brain cortex and premortem blood-derived exosomes found elevated levels of NAAA expression in persons with PD compared to age-matched controls. Furthermore, in vitro experiments showed that the dopaminergic neurotoxins, 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), enhanced NAAA expression and lowered PEA content in human SH-SY5Y cells. A similar effect was observed in dopamine neurons and, subsequently, in microglia following 6-OHDA injection in mice. Importantly, deletion of the Naaa gene or pharmacological inhibition of NAAA activity markedly attenuated both dopamine neuron death and parkinsonian symptoms in mice treated with 6-OHDA or MPTP. The results identify NAAA-regulated PEA signaling as a control node for dopaminergic neuron survival and a potential target for therapeutic intervention in PD.