bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of COVID-19 on Primary Care Mental Health Services: A Descriptive, Cross-Sectional Timeseries of Electronic Healthcare Records
Authors: Bauer-Staeb Clarissa , Davis Alice , Smith Theresa , Wilsher Wendy , Betts David , Eldridge Chris , Griffith Emma , Faraway Julian , Button Katherine 
Published: August 2020

ABSTRACTIntroductionThere are growing concerns about the impact of the COVID-19 pandemic on mental health. With government-imposed restrictions as well as a general burden on healthcare systems, the pandemic has the potential to disrupt the access to, and delivery of, mental healthcare. Ultimately, this could potentially lead to unmet needs of individuals requiring mental health support.MethodsElectronic healthcare records from primary care psychological therapy services (Improving Access to Psychological Therapy) in England were used to examine changes in access to mental health services and service delivery during early stages of the COVID-19 pandemic. A cross-sectional, descriptive timeseries was conducted using data from 1st January 2019 to 24th May 2020 across five NHS trusts to examine patterns in referrals to services (n = 171,823) and appointments taking place (n = 865,902).ResultsThe number of patients accessing mental health services dropped by an average of 55% in the 9 weeks after lockdown was announced, reaching a maximum reduction of 74% in the initial 3 weeks after lockdown in the UK. As referrals began to increase again, there was a relatively faster increase in referrals from Black, Asian, and ethnic minority groups as well an increase in referrals from more densely populated areas. Despite a reduction in access, service providers adapted to infection control guidance by rapidly shifting to remote delivery of care.InterpretationServices were able to rapidly adapt to provide continuity of care in mental healthcare. However, patients accessing services reduced dramatically, potentially placing a future burden on service providers to treat a likely backlog of patients in addition to a possible excess of patients as the long-term consequences of the pandemic become more apparent. Despite the observational nature of the data, which should be noted, the present study can inform the planning of service provision and policy.
The differential immune responses to COVID-19 in peripheral and lung revealed by single-cell RNA sequencing
Authors: Xu Gang , Qi Furong , Li Hanjie , Yang Qianting , Wang Haiyan , Wang Xin , Liu Xiaoju , Zhao Juanjuan , Liao Xuejiao , Liu Yang , Amit Ido , Liu Lei , Zhang Shuye , Zhang Zheng 
Published: August 2020

AbstractUnderstanding the mechanism that leads to immune dysfunction induced by SARS-CoV2 virus is crucial to develop treatment for severe COVID-19. Here, using single cell RNA-seq, we characterized the peripheral blood mononuclear cells (PBMC) from uninfected controls and COVID-19 patients, and cells in paired broncho-alveolar lavage fluid (BALF). We found a close association of decreased dendritic cells (DC) and increased monocytes resembling myeloid-derived suppressor cells (MDSC) which correlated with lymphopenia and inflammation in the blood of severe COVID-19 patients. Those MDSC-like monocytes were immune-paralyzed. In contrast, monocyte-macrophages in BALFs of COVID-19 patients produced massive amounts of cytokines and chemokines, but secreted little interferons. The frequencies of peripheral T cells and NK cells were significantly decreased in severe COVID-19 patients, especially for innate-like T and various CD8+ T cell subsets, compared to health controls. In contrast, the proportions of various activated CD4+ T cell subsets, including Th1, Th2 and Th17-like cells were increased and more clonally expanded in severe COVID-19 patients. Patients’ peripheral T cells showed no sign of exhaustion or augmented cell death, whereas T cells in BALFs produced higher levels of IFNG, TNF, CCL4 and CCL5 etc. Paired TCR tracking indicated abundant recruitment of peripheral T cells to the patients’ lung. Together, this study comprehensively depicts how the immune cell landscape is perturbed in severe COVID-19.
Pulmonary cavitation – an under-recognized late complication of severe COVID-19 lung disease
Authors: Zoumot Zaid , Bonilla Maria-Fernanda , Wahla Ali S. , Shafiq Irfan , Uzbeck Mateen , El-Lababidi Rania M. , Hamed Fadi , Abuzakouk Mohamed , ElKaissi Mahmoud 
Published: August 2020

ABSTRACTBackgroundRadiological findings of the novel coronavirus disease 2019 (COVID-19) pulmonary disease have been well documented and range from scattered ground-glass infiltrates in milder cases to confluent ground-glass change, dense consolidation, and crazy paving in the critically ill, however, lung cavitation has not been described in these patients.ObjectivesTo assess the incidence of pulmonary cavitation and describe its characteristics and evolution.MethodsA retrospective review of all patients admitted to our institution with COVID-19 was undertaken and imaging reviewed to identify patients who developed pulmonary cavitation.ResultsTwelve out of 689 (1.7%) patients admitted to our institution with COVID-19 developed pulmonary cavitation, comprising 3.3% (n = 12/359) of those with COVID-19 pneumonia, and 11% (n = 12/110) of those admitted to the intensive care unit. We describe the imaging characteristics of the cavitation and present the clinical, pharmacological, laboratory, and microbiological parameters for these patients. In this cohort six patients have died while another remains critically ill and unlikely to survive.ConclusionCavitary lung disease in patients with severe COVID-19 disease is not uncommon, and is associated with a high level of morbidity and mortality.
An invasive plant species enhances biodiversity in overgrazed pastures but inhibits its recovery in protected areas
Authors: Losapio Gianalberto , De Moraes Consuelo M. , Dirzo Rodolfo , Dutoit Lilian L. , Tscheulin Thomas , Zouros Nikos , Mescher Mark C. 
Published: August 2020

AbstractAnthropogenic environmental change exposes biological communities to concurrent stressors (e.g., changes in climate and land-use, overexploitation, biotic invasions) that frequently persist over prolonged periods. Predicting and mitigating the consequences of human action on nature therefore requires understanding how exposure to multiple interacting stressors alters biological communities over relevant (e.g., multi-decadal) time periods. Here, we explore the effects of overgrazing and plant species invasion on plant community diversity and ecosystem functioning (productivity), as well as the patterns of recovery of plant communities following cessation of grazing pressure. In a Mediterranean pasture system, we utilized a “natural” experiment involving long-term exclusion of grazers (for 15-25 years in parks) and also conducted short-term grazing-exclusion and invasive species removal experiments. Our results reveal that invasion by a grazing-resistant plant (prickly burnet) has net positive effects on plant diversity under overgrazing conditions but inhibits the recovery of biodiversity once grazing ceases. Furthermore, while the diversity-productivity relationship was found to be positive in pastures, the interactive effects of overgrazing and species invasion appear to disrupt ecosystem functioning and inhibit the recovery of pasture productivity. These findings highlight the potential for prolonged exposure to anthropogenic stressors, such as overgrazing, to cause potentially-irreversible changes in biological communities that, in turn, compromise ecosystem functioning and resilience. In such cases, sustainable ecosystem management may require direct intervention to boost biodiversity resilience against centennial overgrazing.
Adaptive evolution at mRNA editing sites in soft-bodied cephalopods
Authors: Moldovan Mikhail A. , Chervontseva Zoe S. , Bazykin Georgii A. , Gelfand Mikhail S. 
Published: August 2020

AbstractThe bulk of variability in mRNA sequence arises due to mutation – change in DNA sequence which is heritable if it occurs in the germline. However, variation in mRNA can also be achieved by post-translational modification including mRNA editing, changes in mRNA nucleotide sequence that mimic the effect of mutations. Such modifications are not inherited directly; however, as the processes affecting them are encoded in the genome, they have a heritable component, and therefore can be shaped by selection. In soft-bodied cephalopods, adenine-to-inosine RNA editing is very frequent, and much of it occurs at nonsynonymous sites, affecting the sequence of the encoded protein. Here, we show that mRNA editing of individual nonsynonymous sites in cephalopods originates in evolution through substitutions at regions adjacent to these sites. As such substitutions mimic the effect of the substitution at the edited site itself, we hypothesize that they are favored by selection if the inosine is selectively advantageous to adenine at the edited position. Consistent with this hypothesis and with observations onDrosophilaand human editing sites, we show that edited adenines are more frequently substituted with guanine, an informational analogue of inosine, in the course of evolution than their unedited counterparts, and for heavily edited adenines, these transitions are favored by positive selection. Thus, our study shows that coleoid editing sites may enhance adaptation, which, together with distinct evolutionary features ofDrosophilaand human editing sites, points at a general role of RNA editing in the molecular evolution of metazoans.
Rapid and efficientin vivoastrocyte-to-neuron conversion with regional identity and connectivity?
Authors: Wang Lei-Lei , Garcia Carolina Serrano , Zhong Xiaoling , Ma Shuaipeng , Zhang Chun-Li 
Published: August 2020

ABSTRACTIn vivoreprogramming of glia into functional neurons emerges as potential regeneration-based therapeutics for neural injuries or neurological diseases. Recent studies show that AAV-based manipulation of certain factors can rapidly and highly efficiently convert resident glia into functional neurons with brain region-specificity and precise connectivity. Using NEUROD1 as an example, we here show that the presumed astrocytes-converted neurons are essentially endogenous neurons in the adult mouse brain. AAV-mediated co-expression of NEUROD1 and a reporter indeed specifically, rapidly, and efficiently induces numerous reporter-labeled neurons. However, these neurons cannot be traced back to quiescent or reactive astrocytes by using stringent lineage-mapping strategies. Conversely, reporter-labeled neurons cannot be detected when NEUROD1 is strictly expressed in adult brain astrocytes. Through a retrograde labeling approach, our results rather reveal that endogenous neurons are the cell source for NEUROD1-induced reporter-labeled neurons. These results underline the indispensable value of stringent lineage-tracing strategies and beg for cautious interpretation of thein vivoreprogramming phenomena.
Effects of Peripheral Haptic Feedback on Intracortical Brain-Computer Interface Control and Associated Sensory Responses in Motor Cortex
Authors: Deo Darrel R. , Rezaii Paymon , Hochberg Leigh R. , Okamura Allison M. , Shenoy Krishna V. , Henderson Jaimie M. 
Published: August 2020

AbstractIntracortical brain-computer interfaces (iBCIs) provide people with paralysis a means to control devices with signals decoded from brain activity. Despite recent impressive advances, these devices still cannot approach able-bodied levels of control. To achieve naturalistic control and improved performance of neural prostheses, iBCIs will likely need to include proprioceptive feedback. With the goal of providing proprioceptive feedback via mechanical haptic stimulation, we aim to understand how haptic stimulation affects motor cortical neurons and ultimately, iBCI control. We provided skin shear haptic stimulation as a substitute for proprioception to the back of the neck of a person with tetraplegia. The neck location was determined via assessment of touch sensitivity using a monofilament test kit. The participant was able to correctly report skin shear at the back of the neck in 8 unique directions with 65% accuracy. We found motor cortical units that exhibited sensory responses to shear stimuli, some of which were strongly tuned to the stimuli and well modeled by cosine-shaped functions. We also demonstrated online iBCI cursor control with continuous skin-shear feedback driven by decoded command signals. Cursor control performance increased slightly but significantly when the participant was given haptic feedback, compared to the purely visual feedback condition.
Cellular pathways of calcium transport and concentration towards mineral formation in sea urchin larvae
Authors: Kahil Keren , Varsano Neta , Sorrentino Andrea , Pereiro Eva , Rez Peter , Weiner Steve , Addadi Lia 
Published: August 2020

AbstractSea urchin larvae have an endoskeleton consisting of two calcitic spicules. The primary mesenchyme cells (PMCs) are the cells that are responsible for spicule formation. PMCs endocytose sea water from the larval internal body cavity into a network of vacuoles and vesicles, where calcium ions are concentrated until they precipitate in the form of amorphous calcium carbonate (ACC). The mineral is subsequently transferred to the syncytium, where the spicule forms. Using cryo-soft X-ray microscopy (cryo-SXM) we imaged intra-cellular calcium-containing particles in the PMCs and acquired Ca-L2,3X-ray absorption near edge spectra (XANES) of these Ca-particles. Using the pre-peak/main peak (L2’/ L2) intensity ratio, which reflects the atomic order in the first Ca coordination shell, we determined the state of the calcium ions in each particle. The concentration of Ca in each of the particles was also determined by the integrated area in the main Ca absorption peak. We observed about 700 Ca-particles with order parameters, L2’/ L2, ranging from solution to hydrated and anhydrous ACC, and with concentrations ranging between 1-15 M. We conclude that in each cell the calcium ions exist in a continuum of states. This implies that most, but not all water, is expelled from the particles. This cellular process of calcium concentration may represent a widespread pathway in mineralizing organisms.SignificanceOrganisms form mineralized skeletons, many of which are composed of calcium salts. Marine organisms extract calcium ions from sea water. One of the main unresolved issues is how organisms concentrate calcium by more than 3 orders of magnitude, to achieve mineral deposition in their skeleton. Here we determine the calcium state in each of the calcium-containing vesicles inside the spicule-building cells of sea urchin larvae. We show that within one cell there is a wide range of concentrations and states from solution to solid. We hypothesize that calcium concentration increases gradually in each vesicle, starting from sea water levels and until mineral is deposited. This model might well be relevant to other phyla, thus advancing the understanding of biomineralization processes.
Cooperative Binding of Transcription Factors is a Hallmark of Active Enhancers
Authors: Rao Satyanarayan , Ahmad Kami , Ramachandran Srinivas 
Published: August 2020

AbstractEnhancers harbor binding motifs that recruit transcription factors (TFs) for gene activation. While cooperative binding of TFs at enhancers is known to be critical for transcriptional activation of a handful of developmental enhancers, the extent TF cooperativity genome-wide is unknown. Here, we couple high-resolution nuclease footprinting with single-molecule methylation profiling to characterize TF cooperativity at active enhancers in theDrosophilagenome. Enrichment of short MNase-protected DNA segments indicates that the majority of enhancers harbor two or more TF binding sites, and we uncover protected fragments that correspond to co-bound sites in thousands of enhancers. We integrate MNase-seq, methylation accessibility profiling, and CUT&RUN chromatin profiling as a comprehensive strategy to characterize co-binding of the Trithorax-like (TRL) DNA binding protein and multiple other TFs and identify states where an enhancer is bound by no TF, by either single factor, by multiple factors, or where binding sites are occluded by nucleosomes. From the analysis of co-binding, we find that cooperativity dominates TF bindingin vivoat a majority of active enhancers. TF cooperativity can occur without apparent protein-protein interactions and provides a mechanism to effectively clear nucleosomes and promote enhancer function.
The anti-sigma factor MucA is required for viability inPseudomonas aeruginosa
Authors: Schofield Melissa C. , Rodriguez Daniela , Kidman Amanda A. , Cassin Erin K. , Michaels Lia A. , Campbell Elizabeth A. , Jorth Peter A. , Tseng Boo Shan 
Published: August 2020

ABSTRACTDuring decades-long infections in the cystic fibrosis (CF) airway,Pseudomonas aeruginosaundergoes selection. One bacterial genetic adaptation often observed in CF isolates ismucAmutations. MucA inhibits the sigma factor AlgU. Mutations inmucAlead to AlgU misregulation, resulting in a mucoid phenotype that is associated with poor CF disease outcomes. Due to its ability to be mutated,mucAis assumed to be dispensable for bacterial viability. Here we show that, paradoxically, a portion ofmucAis essential inP. aeruginosa. We demonstrate thatmucAis no longer required in a strain lackingalgU, thatmucAalleles encoding for proteins that do not bind to AlgU are insufficient for viability, and thatmucAis no longer essential in mutant strains containing AlgU variants with reduced sigma factor activity. Furthermore, we found that overexpression ofalgUprevents cell growth in the absence of MucA, and that this phenotype can be rescued by overproduction of RpoD, the housekeeping sigma factor. Together, these results suggest that in the absence of MucA, the inability to regulate AlgU activity results in the loss of bacterial viability. Finally, we speculate that essentiality of anti-sigma factors that regulate envelope function may be a widespread phenomenon in bacteria.
FLIMJ: an open-source ImageJ toolkit for fluorescence lifetime image data analysis
Authors: Gao Dasong , Barber Paul R , Chacko Jenu V , Sagar Md Abdul Kader , Rueden Curtis T , Grislis Aivar R , Hiner Mark C , Eliceiri Kevin W 
Published: August 2020

AbstractIn the field of fluorescence microscopy, there is continued demand for dynamic technologies that can exploit the complete information from every pixel of an image. One imaging technique with proven ability for yielding additional information from fluorescence imaging is Fluorescence Lifetime Imaging Microscopy (FLIM). FLIM allows for the measurement of how long a fluorophore stays in an excited energy state and is affected by changes in its chemical microenvironment, such as proximity to other fluorophores, pH, and hydrophobic regions. This ability to provide information about the microenvironment has made FLIM a powerful tool for cellular imaging studies ranging from metabolic measurement to measuring distances between proteins. The increased use of FLIM has necessitated the development of computational tools for integrating FLIM analysis with image and data processing. To address this need, we have created FLIMJ, an ImageJ plugin, and toolkit that allows for easy use and development of extensible image analysis workflows with FLIM data. Built on the FLIMLib decay curve fitting library and the ImageJ Ops framework, FLIMJ offers FLIM fitting routines with seamless integration with other ImageJ components, and the ability to be extended to create complex FLIM analysis workflows. Building on ImageJ Ops also enables FLIMJ’s routines to be used with Jupyter notebooks and integrate naturally with science-friendly programming in, e.g., Python and Groovy. We show the extensibility of FLIMJ in two analysis scenarios: lifetime-based image segmentation and image colocalization. We also validate the fitting routines by comparing against industry FLIM analysis standards.
BARcode DEmixing through Non-negative Spatial Regression (BarDensr)
Authors: Chen Shuonan , Loper Jackson , Chen Xiaoyin , Vaughan Alex , Zador Anthony M. , Paninski Liam 
Published: August 2020

AbstractModern spatial transcriptomics methods can target thousands of different types of RNA transcripts in a single slice of tissue. Many biological applications demand a high spatial density of transcripts relative to the imaging resolution, leading to partial mixing of transcript rolonies in many voxels; unfortunately, current analysis methods do not perform robustly in this highly-mixed setting. Here we develop a new analysis approach,BARcode DEmixing through Non-negative Spatial Regression(BarDensr): we start with a generative model of the physical process that leads to the observed image data and then apply sparse convex optimization methods to estimate the underlying (demixed) rolony densities. We apply Bar-Densr to simulated and real data and find that it achieves state of the art signal recovery, particularly in densely-labeled regions or data with low spatial resolution. Finally, BarDensr is fast and parallelizable. We provide open-source code as well as an implementation for the ‘NeuroCAAS’ cloud platform.Author SummarySpatial transcriptomics technologies allow us to simultaneously detect multiple molecular targets in the context of intact tissues. These experiments yield images that answer two questions: which kinds of molecules are present, and where are they located in the tissue? In many experiments (e.g., mapping RNA expression in fine neuronal processes), it is desirable to increase the signal density relative to the imaging resolution. This may lead to mixing of signals from multiple RNA molecules into single imaging voxels; thus we need todemixthe signals from these images. Here we introduce BarDensr, a new computational method to perform this demixing. The method is based on a forward model of the imaging process, followed by a convex optimization approach to approximately ‘invert’ mixing induced during imaging. This new approach leads to significantly improved performance in demixing imaging data with dense expression and/or low spatial resolution.
Genetic diversity of maize landraces from the South-West of France
Authors: Diaw Yacine , Tollon-Cordet Christine , Charcosset Alain , Nicolas Stéphane , Madur Delphine , Ronfort Joëlle , David Jacques , Gouesnard Brigitte 
Published: August 2020

AbstractFrom the 17th century until the arrival of hybrids in 1960s, maize landraces were cultivated in the South-West of France, a traditional region for maize cultivation. A set of landraces were collected in this region between the 1950s and 1980s and were then conservedex situin a germplam collection. Previous studies using molecular markers on approx. twenty landraces fo this region showed that they belonged to a Pyrenees-Galicia Flint genetic group and originated from hybridization between Caribbean and Northern Flint germplasms introduced in Europe. In this study, we assessed the structure and genetic diversity of 194 SWF maize landraces to elucidate their origin, using a 50K SNP array and a bulk DNA approach. We identified two weakly differentiated genetic groups, one in the Western part and the other in the Eastern part. We highlighted the existence of a longitudinal gradient along the SWF area that was probably maintained through the interplay between genetic drifts and restricted gene flows, rather than through differential climatic adaptation. The contact zone between the two groups observed near the Garonne valley may be the result of these evolutionnary forces. We found only few significant cases of hybridization between Caribbean and Northern Flint germplasms in the region. We also found gene flows from various maize genetic groups to SWF landraces. Thus, we assumed that SWF landraces had a multiple origin with a slightly higher influence of Tropical germplasm in the West and preponderance of Northern Flint germplasm in the East.