bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bronchoscopy on Intubated COVID-19 Patients is Associated with Low Infectious Risk to Operators at a High-Volume Center Using an Aerosol-minimizing Protocol
Authors: Gao Catherine A. , Bailey Joseph I. , Walter James M. , Coleman John M. , Malsin Elizabeth S. , Argento A. Christine ,   NU COVID Investigators, Wunderink Richard G. , Smith Sean B. 
Published: September 2020

ABSTRACTBackgroundThe coronavirus disease 2019 (COVID-19) pandemic raised concern for exposure to healthcare providers through aerosol generating procedures, such as bronchoalveolar lavage (BAL). Current society guidelines recommended limiting use of BAL to reduce operators’ risk for infection, yet data on the infection rate for providers after BAL is sparse. Since March 2020, our institution used a modified protocol to perform over 450 BALs on intubated COVID-19 patients. We therefore sought to describe the subsequent infectious risks to providers associated with BAL.MethodsFifty-two pulmonary and critical care providers (faculty and fellows) at our tertiary-care, urban medical center were surveyed. Survey participants were asked to provide the number of BALs on COVID-19 patients they performed, the number of weeks they cared for intensive care unit (ICU) patients with COVID-19, and the results of any SARS-CoV-2 testing that they received. Participants were asked to assess the difficulty of BAL on intubated COVID-19 patients as compared to routine ICU BAL using a numeric perceived difficulty score ranging from 1 (easier) to 10 (harder).ResultsWe received forty-seven responses from fifty-two surveyed (90% response rate), with 2 declining to participate. Many respondents (19/45, 42%) spent >5 weeks on an ICU service with COVID-19 patients. The number of BALs performed by providers ranged from 0 to >60. Sixteen of the 35 providers (46%) who performed BALs underwent at least one nasopharyngeal (NP) swab to test for SARS-CoV-2, but none were positive. Twenty-seven of the 35 providers (77%) who performed BALs underwent SARS- CoV-2 serology testing, and only one (3.7%) was positive. Respondents indicated occasionally not being able to follow aerosol-minimizing steps but overall felt BALs in COVID-19 patients was only slightly more difficult than routine bronchoscopy.DiscussionAt a high-volume center having performed >450 BALs on intubated COVID-19 patients with aerosol-limiting precautions, our survey of bronchoscopists found no positive NP SARS-CoV-2 tests and only one positive antibody test result. While the optimal role for COVID-19 BAL remains to be determined, these data suggest that BAL can be safely performed in intubated COVID-19 patients if experienced providers take precautions to limit aerosol generation and wear personal protective equipment.
Viral shedding dynamics reveals sputum as a reliable and cost-saving specimen for SARS-CoV-2 diagnosis within the first 10 days since symptom onset: A prospective cohort study
Authors: Levican Jorge , Almonacid Leonardo I. , Valenzuela Gonzalo , García-Salum Tamara , Rojas Luis , Serrano Eileen , Pardo-Roa Catalina , Salinas Erick , Avendaño María José , Perazzo Fabiola , Díaz Luis Antonio , Valderrama Sebastián , Ortega Marcos , Toro Adriana , Montecinos Viviana , Riquelme Arnoldo , Medina Rafael A. 
Published: September 2020

AbstractBackgroundCoronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome virus (SARS-CoV-2) is challenging global public health, due to an increasing demand for testing and the shortage of diagnostic supplies. Nasopharyngeal swab (NPS) is considered the optimal sample for SARS-CoV2 diagnosis and sputum (SPT) has been proposed as an economic alternative. However, the temporal concordance of diagnosis in NPS and SPT has not been addressed.MethodsThrough a longitudinal study we compared the shedding dynamics of SARS-CoV-2 RNA evaluated by RT-qPCR in serially collected SPT and NPS obtained from 82 ambulatory and hospitalized patients during acute infection and convalescence. The concordance during the follow-up and cost analysis between both collected specimens was evaluated.FindingsWe analyzed 379 samples, 177 NPS and 202 SPT. The highest proportion of positive samples was detected within the first 15 days after the symptoms onset. The median time of positivity was higher for NPS (median= 25 days) than SPT (median= 21 days). There was no significant difference in the median RT-qPCR CTvalues between both sample types. The temporal categorization of matched-paired samples indicated substantial correlation (r=0·6023) and substantial agreement (87·23%) during the first ten days since symptoms onset (kappa = 0·697). A cost analysis demonstrated a significant saving when the SPT specimen was used.InterpretationSputum is a feasible and cost-saving alternative to NPS, providing an equivalent value for the detection and follow-up of SARS-CoV-2 RNA.FundingAgencia Nacional de Investigación y Desarrollo (ANID) of Chile, NIH-NIAID USA.
Dissecting the landscape of activated CMV-stimulated CD4+ T cells in human by linking single-cell RNA-seq with T-cell receptor sequencing
Authors: Lyu Menghua , Wang Shiyu , Gao Kai , Wang Longlong , Li Bin , Tian Lei 
Published: September 2020

AbstractCD4 T cell is crucial in CMV infection, but its role is still unclear during this process. Here, we present a single-cell RNA-seq together with T cell receptor (TCR) sequencing to screen the heterogenicity and potential function of CMV pp65 reactivated CD4+ T cell subsets from human peripheral blood, and unveil their potential interactions. Notably, Treg composed the major part of these reactivated cells. Treg gene expression data revealed multiple transcripts of both inflammatory and inhibitory functions. Additionally, we describe the detailed phenotypes of CMV-reactivated effector-memory (Tem), cytotoxic T (CTL), and naïve T cells at the single-cell resolution, and implied the direct derivation of CTL from naïve CD4+ T cells. By analyzing the TCR repertoire, we identified a clonality in stimulated Tem and CTLs, and a tight relationship of Tem and CTL showing a large share in TCR. This study provides clues for understanding the function of CD4+ T cells subsets and unveils their interaction in CMV infection, and may promote the development of CMV immunotherapy.
Discriminating the Single-cell Gene Regulatory Networks of Human Pancreatic Islets: A Novel Deep Learning Application
Authors: Turki Turki , Taguchi Y-h. 
Published: September 2020

AbstractAnalyzing single-cell pancreatic data would play an important role in understanding various metabolic diseases and health conditions. Due to the sparsity and noise present in such single-cell gene expression data, analyzing various functions related to the inference of gene regulatory networks, derived from single-cell data, remains difficult, thereby posing a barrier to the deepening of understanding of cellular metabolism. Since recent studies have led to the reliable inference of single-cell gene regulatory networks (SCGRNs), the challenge of discriminating between SCGRNs has now arisen. By accurately discriminating between SCGRNs (e.g., distinguishing SCGRNs of healthy pancreas from those of T2D pancreas), biologists would be able to annotate, organize, visualize, and identify common patterns of SCGRNs for metabolic diseases. Such annotated SCGRNs could play an important role in speeding up the process of building large data repositories. In this study, we aimed to contribute to the development of a novel deep learning (DL) application. First, we generated a dataset consisting of 224 SCGRNs belonging to both T2D and healthy pancreas and made it freely available. Next, we chose seven DL architectures, including VGG16, VGG19, Xception, ResNet50, ResNet101, DenseNet121, and DenseNet169, trained each of them on the dataset, and checked prediction based on a test set. We evaluated the DL architectures on an HP workstation platform with a single NVIDIA GeForce RTX 2080Ti GPU. Experimental results on the whole dataset, using several performance measures, demonstrated the superiority of VGG19 DL model in the automatic classification of SCGRNs, derived from the single-cell pancreatic data.
A Metabolomic Study of Cervical Dystonia
Authors: Liu Chang , Scorr Laura , Kilic-Berkmen Gamze , Cotton Adam , Factor Stewart A. , Freeman Alan , Tran ViLinh , Liu Ken , Uppal Karan , Jones Dean , Jinnah H. A. , Sun Yan V. 
Published: September 2020

AbstractBackgroundCervical dystonia is the most common of the adult-onset focal dystonias. Most cases are idiopathic. The current view is that cervical dystonia may be caused by some combination of genetic and environmental factors. Genetic contributions have been studied extensively, but there are few studies of other factors.ObjectiveTo conduct an exploratory metabolomics analysis of cervical dystonia to identify potentially abnormal metabolites or altered biological pathways.MethodsPlasma samples from 100 cases with idiopathic cervical dystonia and 100 controls were compared using liquid chromatography coupled with mass spectrometry-based metabolomics.ResultsA total of 7,346 metabolic features remained after quality control, and 289 demonstrated significant differences between cases and controls, depending on statistical criteria chosen. Pathway analysis revealed 9 biological processes to be significantly associated at p<0.05, 5 pathways were related to carbohydrate metabolism, 3 pathways were related to lipid metabolism.ConclusionThis is the first large scale metabolomics study for any type of dystonia. The results may provide potential novel insights into the biology of cervical dystonia.
Student-focused development of a next-generation centrifuge force microscope
Authors: Tompkins K.J. , Venkatesh N. , Berscheid E.T. , Adamek A.J. , Beckman A.P. , Esler M.A. , Evans A.C. , Everett B.A. , Houtti M. , Koo H. , Litzau L.A. , Nelson A.T. , Peterson T.M. , Reid T.A. , Evans R.L. , Gordon W.R. 
Published: September 2020

ABSTRACTAdvanced biological molecule force probing methods such as atomic force microscopy and optical tweezers used to quantify forces at the single-molecule level are expensive and require extensive training and technical knowledge. However, the technologies underlying a centrifuge force microscope (CFM) are relatively straight forward, allowing for construction by labs with relatively low budgets and minimal training. Design ideas from previously constructed CFMs served as a guide in the development of this CFM. There were two primary goals: first, to develop an inexpensive, functional CFM using off-the-shelf and 3D printed parts; and second, to do so in the context of providing an educational experience for a broad range of students. The team included high school students and undergraduates from local high schools, the University of Minnesota, and other local higher education institutions. This project created an environment for student-focused development of the CFM that fostered active learning, individual ownership, as well as excellence in research. The instrument discussed herein represents a fully functional CFM designed and built by a postdoctoral researcher and a graduate student who together mentored several high school and undergraduate students.STATEMENT OF SIGNIFICANCEThe presented centrifuge force microscope (CFM) builds on features of existing designs specifically engineered for probing macromolecular force interactions at the single-molecule level. In the coming years, more versatile and modular CFM designs will be utilized in the force spectroscopy field, and the presented design is a step in that direction. In addition to constructing a functional instrument, true student ownership of the project design was equally an end goal. Students from high school through graduate school were included, and the project was structured so that everyone was seen as peers. This active learning project allowed students to acquire scientific concepts and techniques and apply them to real-life situations.
Feedback from retinal ganglion cells to the inner retina
Authors: Vlasiuk Anastasiia , Asari Hiroki 
Published: September 2020

AbstractRetinal ganglion cells (RGCs) are thought to be strictly postsynaptic within the retina. They carry visual signals from the eye to the brain, but do not make chemical synapses onto other retinal neurons. Nevertheless, they form gap junctions with other RGCs and amacrine cells, providing possibilities for RGC signals to feed back into the inner retina. Here we identified such feedback circuitry in the salamander and mouse retinas. First, using biologically inspired circuit models, we found mutual inhibition among RGCs of the same type. We then experimentally determined that this effect is mediated by gap junctions with amacrine cells. Finally, we found that this negative feedback lowers RGC visual response gain without affecting feature selectivity. The principal neurons of the retina therefore participate in a recurrent circuit much as those in other brain areas, not being a mere collector of retinal signals, but are actively involved in visual computations.
Freeform printing of heterotypic tumor models within cell-laden microgel matrices
Authors: Molley Thomas G. , Jalandhra Gagan K. , Nemec Stephanie R. , Tiffany Aleczandria S. , Harley Brendan A. C. , Hung Tzong-tyng , Kilian Kristopher A. 
Published: September 2020

AbstractThe tissue microenvironment is comprised of a complex assortment of multiple cell types, matrices, membranes and vessel structures. Emulating this complex and often hierarchical organizationin vitrohas proved a considerable challenge, typically involving segregation of different cell types using layer-by-layer printing or lithographically patterned microfluidic devices. Bioprinting in granular materials is a new methodology with tremendous potential for tissue fabrication. Here, we demonstrate the first example of a complex tumor microenvironment that combines direct writing of tumor aggregates, freeform vasculature channels, and a tunable macroporous matrix as a model to studying metastatic signaling. Our photocrosslinkable microgel suspensions yield local stiffness gradients between particles and the intervening space, while enabling the integration of virtually any cell type. Using computational fluid dynamics, we show that removal of a sacrificial Pluronic ink defines vessel-mimetic channel architectures for endothelial cell linings. Pairing this vasculature with 3D printing of melanoma aggregates, we find that tumor cells within proximity migrated into the prototype vasculature. Together, the integration of perfusable channels with multiple spatially defined cell types provides new avenues for modelling development and disease, with scope for fundamental research and drug development.
Somatosensory Cortex of Macaque Monkeys is Designed for Opposable Thumb
Authors: Lazar Leslee , Chand Prem , Rajan Radhika , Mohammed Hisham , Jain Neeraj 
Published: September 2020

AbstractThe evolution of opposable thumb has enabled fine grasping ability and precision grip, which led to the capacity for fine manipulation of objects and refined tool use. Since tactile inputs to an opposable thumb are often spatially and temporally out of synch with inputs from the fingers, we hypothesized that inputs from the opposable thumb would be processed in an independent module in the primary somatosensory cortex (area 3b). Here we show that in area 3b of macaque monkeys, most neurons in the thumb representation do not respond to tactile stimulation of other digits and receive few intrinsic cortical inputs from other digits. However, neurons in the representations of other digits respond to touch on any of the four digits and are significantly more interconnected in the cortex. The thumb inputs are thus processed in an independent module, whereas there is significantly more inter-digital information exchange between the other digits. This cortical organization reflects behavioral use of the hand with an opposable thumb.
Emergence of Lyme disease on treeless islands in Scotland, UK
Authors: Millins Caroline , Leo Walter , MacInnes Isabell , Ferguson Johanne , Charlesworth Graham , Nayar Donald , Davison Reece , Yardley Jonathan , Kilbride Elizabeth , Huntley Selene , Gilbert Lucy , Viana Mafalda , Johnson Paul , Biek Roman 
Published: September 2020

AbstractLyme disease (LD) is typically associated with forested habitats but has recently emerged on treeless islands in the Western Isles of Scotland. This has created a need to understand the environmental and human components of LD risk in open habitats. This study quantified both elements of LD risk and compared these between treeless islands with high and low LD incidence. We found high LD incidence was linked to higher prevalence in ticks (6.4% vs 0.4%) and increased human tick bite exposure. Most reported tick bites (72.7%) were within 1km of the home address and commonly in gardens. Residents on islands with high LD incidence reported increasing problems with ticks and suggested changing deer distribution as a potential driver. This study highlights the benefits to public health of an integrated approach to understand the factors contributing to LD emergence and a need to evaluate LD ecology in treeless habitats more broadly.
Plankton Planet: ‘seatizen’ oceanography to assess open ocean life at the planetary scale
Authors: de Vargas Colomban , Pollina Thibaut , Romac Sarah , Le Bescot Noan , Henry Nicolas , Berger Calixte , Colin Sébastien , Haëntjens Nils , Carmichael Margaux , Le Guen David , Decelle Johan , Mahé Frédéric , Malpot Emmanuel , Beaumont Carole , Hardy Michel ,   the planktonauts, the Plankton Planet team, Guiffant Damien , Probert Ian , Gruber David F. , Allen Andy , Gorsky Gabriel , Follows Mick , Cael Barry B. , Pochon Xavier , Troublé Romain , Lombard Fabien , Boss Emmanuel , Prakash Manu 
Published: September 2020

AbstractIn every liter of seawater there are between 10 and 100 billion life forms, mostly invisible, called plankton, which form the largest and most dynamic ecosystem on our planet, at the heart of global ecological and economic processes. While physical and chemical parameters of planktonic ecosystems are fairly well measured and modelled at the planetary scale, but biological data are still scarce due to the extreme cost and relative inflexibility of the classical vessels and instruments used to explore marine biodiversity. Here we introduce ‘Plankton Planet’, an initiative whose goal is to merge the creativity of researchers, makers, and mariners to (i) develop frugal scientific instrumentation and protocols to assess the genetic and morphological diversity of plankton life, and (ii) organize their systematic deployment through fleets of volunteer sailors, fishermen, or cargo-ships to generate comparable and open-access plankton data across global and long-term spatio-temporal scales. As proof-of-concept, we show how 20 crews of sailors (“planktonauts”) were abl to sample plankton biomass from the world surface ocean in a single year, generating the first citizen-based, planetary dataset of plankton biodiversity based on DNA barcodes. The quality of this dataset is comparable to that generated by Tara Oceans and is not biased by the multiplication of samplers. This dataset has unveiled significant genetic novelty and can be used to explore the taxonomic and ecological diversity of plankton at both regional and global scales. This pilot project paves the way for construction of a miniaturized, modular, evolvable, affordable and open-source citizen field-platform that will allow systematic assessment of the eco/morpho/genetic variation of aquatic ecosystems across the dimensions of the Earth system.
ACE2 and SARS-CoV-2 Expression in the Normal and COVID-19 Pancreas
Authors: Kusmartseva Irina , Wu Wenting , Syed Farooq , Van Der Heide Verena , Jorgensen Marda , Joseph Paul , Tang Xiaohan , Candelario-Jalil Eduardo , Yang Changjun , Nick Harry , Harbert Jack L. , Posgai Amanda , Lloyd Richard , Cechin Sirlene , Pugliese Alberto , Campbell-Thompson Martha , Vander Heide Richard S. , Evans-Molina Carmella , Homann Dirk , Atkinson Mark A. 
Published: September 2020

SUMMARYDiabetes is associated with increased mortality from Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Given literature suggesting a potential association between SARS-CoV-2 infection and diabetes induction, we examined pancreatic expression of the key molecule for SARS-CoV-2 infection of cells, angiotensin-converting enzyme-2 (ACE2). Specifically, we analyzed five public scRNAseq pancreas datasets and performed fluorescencein situhybridization, Western blotting, and immunolocalization for ACE2 with extensive reagent validation on normal human pancreatic tissues across the lifespan, as well as those from coronavirus disease 2019 (COVID-19) patients. Thesein silicoandex vivoanalyses demonstrated pancreatic expression of ACE2 is prominent in pancreatic ductal epithelium and the microvasculature, with rare endocrine cell expression of this molecule. Pancreata from COVID-19 patients demonstrated multiple thrombotic lesions with SARS-CoV-2 nucleocapsid protein expression primarily limited to ducts. SARS-CoV-2 infection of pancreatic endocrine cells, via ACE2, appears an unlikely central pathogenic feature of COVID-19 as it relates to diabetes.
The ups and downs of amino acid co-evolution: evolutionary Stokes and anti-Stokes shifts
Authors: Youssef Noor , Susko Edward , Roger Andrew J. , Bielawski Joseph P. 
Published: September 2020

AbstractThe most fundamental form of epistasis occurs between residues within a protein. Epistatic interactions can have significant consequences for evolutionary dynamics. For example, a substitution to a deleterious amino acid may be compensated for by replacements at other sites which increase its propensity (a function of its average fitness) over time - this is the evolutionary Stokes shift. We discovered that an opposite trend -the decrease in amino acid propensity with time-can also occur via the same epistatic dynamics. We define this novel and pervasive phenomenon as the evolutionary anti-Stokes shift. Our extensive simulations of three natural proteins show that evolutionary Stokes and anti-Stokes shifts occur with similar frequencies and magnitudes across the protein. This high-lights that decreasing amino acid propensities, on their own, are not conclusive evidence of adaptive responses to a changing environment. We find that stabilizing substitutions are often permissive (i.e., expand potential evolutionary paths) whereas destabilizing substitutions are restrictive. We show how these dynamics explain the variations in amino acid propensities associated with both evolutionary shifts in propensities.
Modeling stem cell nucleus mechanics using confocal microscopy
Authors: Kennedy Z , Newberg J , Goelzer M , Judex Stefan , Fitzpatrick CK , Uzer G 
Published: September 2020

AbstractNuclear mechanics is emerging as a key component of stem cell function and differentiation. While changes in nuclear structure can be visually imaged with confocal microscopy, mechanical characterization of the nucleus and its sub-cellular components require specialized testing equipment. A computational model permitting cell-specific mechanical information directly from confocal and atomic force microscopy of cell nuclei would be of great value. Here, we developed a computational framework for generating finite element models of isolated cell nuclei from multiple confocal microscopy scans and simple atomic force microscopy (AFM) tests. Confocal imaging stacks of isolated mesenchymal stem cells (MSC) were converted into finite element models and siRNA-mediated LaminA/C depletion isolated chromatin and LaminA/C structures. Using AFM-measured experimental stiffness values, a set of conversion factors were determined for both chromatin and LaminA/C to map the voxel intensity of the original images to the element stiffness, allowing the prediction of nuclear stiffness in an additional set of other nuclei. The developed computational framework will identify the contribution of a multitude of sub-nuclear structures and predict global nuclear stiffness of multiple nuclei based on simple nuclear isolation protocols, confocal images and AFM tests.