bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of a novel, low-cost, scalable vaporized hydrogen peroxide system for sterilization of N95 respirators and other COVID-19 related personal protective equipment
Authors: Dave Nikhil , Pascavis Katie Sue , Patterson John , Wallace David , Chowdhury Abhik , Abbaszadegan Morteza , Alum Absar , Herckes Pierre , Zhang Zhaobo , Kozicki Michael , Forzani Erica , Mora S. Jimena , Chang Josh , Ewell Clinton , Smith Tyler , Naufel Mark 
Published: June 2020

AbstractDue to the virulence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen responsible for the respiratory disease termed COVID-19, there has been a significant increase in demand for surgical masks and N95 respirators in medical clinics as well as within communities operating during the COVID-19 epidemic. Thus, community members, business owners, and even medical personnel have resorted to alternative methods for sterilizing face coverings and N95 respirators for reuse. While significant work has shown that vaporized hydrogen peroxide (VHP) can be used to sterilize N95 respirators, the cost and installation time for these sterilization systems limit their accessibility. To this end, we have designed and constructed a novel, cost-effective, and scalable VHP system that can be used to sterilize N95 respirators and other face coverings for clinical and community applications. N95 respirators inoculated with P22 bacteriophage showed a greater than 6-log10reduction in viral load when sterilized in the VHP system for one 60-minute cycle. Further, N95 respirators treated with 20 cycles in this VHP system showed comparable filtration efficiency to untreated N95 respirators in a 50 to 200 nanometer particulate challenge filtration test. While a 23% average increase in water droplet roll-off time was observed for N95 respirators treated with 5 cycles in the sterilization, no breakdown in fluid resistance was detected. These data suggest that our VHP system is effective in sterilizing N95 respirators and other polypropylene masks for reuse. Relating to the present epidemic, deployment of this system reduces the risk of COVID-19 community transmission while conserving monetary resources otherwise spent on the continuous purchase of disposable N95 respirators and other face coverings. In summary, this novel, scientifically validated sterilization system can be easily built at a low cost and implemented in a wide range of settings.
A direct RT-qPCR approach to test large numbers of individuals for SARS-CoV-2
Authors: Maricic Tomislav , Nickel Olaf , Aximu-Petri Ayinuer , Essel Elena , Gansauge Marie , Kanis Philipp , Macak Dominik , Riesenberg Stephan , Bokelmann Lukas , Zeberg Hugo , Meyer Matthias , Borte Stephan , Pääbo Svante 
Published: June 2020

AbstractSARS-CoV-2 causes substantial morbidity and mortality in elderly and immunocompromised individuals, particularly in retirement homes, where transmission from asymptomatic staff and visitors may introduce the infection. Here we present a cheap and fast approach to detect SARS-CoV-2 in single or pooled gargle lavages (“mouthwashes”). With this approach, we test all staff at a nursing home daily over a period of three weeks in order to reduce the risk that the infection penetrates the facility. This or similar approaches could be implemented to protect hospitals, nursing homes and other institutions in this and future viral epidemics.
Reproducibility in the UK Biobank of Genome-Wide Significant Signals Discovered in Earlier Genome-wide Association Studies
Authors: O’Sullivan Jack W. , Ioannidis John P. A. 
Published: June 2020

AbstractWith the establishment of large biobanks, discovery of single nucleotide polymorphism (SNPs) that are associated with various phenotypes has been accelerated. An open question is whether SNPs identified with genome-wide significance in earlier genome-wide association studies (GWAS) are replicated also in later GWAS conducted in biobanks. To address this question, the authors examined a publicly available GWAS database and identified two, independent GWAS on the same phenotype (an earlier, “discovery” GWAS and a later, replication GWAS done in the UK biobank). The analysis evaluated 136,318,924 SNPs (of which 6,289 had reached p<5e-8 in the discovery GWAS) from 4,397,962 participants across nine phenotypes. The overall replication rate was 85.0% and it was lower for binary than for quantitative phenotypes (58.1% versus 94.8% respectively). There was a18.0% decrease in SNP effect size for binary phenotypes, but a 12.0% increase for quantitative phenotypes. Using the discovery SNP effect size, phenotype trait (binary or quantitative), and discovery p-value, we built and validated a model that predicted SNP replication with area under the Receiver Operator Curve = 0.90. While non-replication may often reflect lack of power rather than genuine false-positive findings, these results provide insights about which discovered associations are likely to be seen again across subsequent GWAS.
Explainable CNN-attention Networks (C-Attention Network) for Automated Detection of Alzheimer’s Disease
Authors: Wang Ning , Chen Mingxuan , Subbalakshmi K.P. 
Published: June 2020

AbstractIn this work we propose three explainable deep learning architectures to automatically detect patients with Alzheimer’s disease based on their language abilities. The architectures use: (1) only the part-of-speech features; (2) only language embedding features and (3) both of these feature classes via a unified architecture. We use self-attention mechanisms and interpretable 1-dimensional Convolutional Neural Network (CNN) to generate two types of explanations of the model’s action: intra-class explanation and inter-class explanation. The inter-class explanation captures the relative importance of each of the different features in that class, while the inter-class explanation captures the relative importance between the classes. Note that although we have considered two classes of features in this paper, the architecture is easily expandable to more classes because of its modularity. Extensive experimentations and comparison with several recent models show that our method outperforms these methods with an accuracy of 92.2% and F1 score of 0.952 on the DementiaBank dataset while being able to generate explanations. We show by examples, how to generate these explanations using attention values.
Modulation of ferroptosis sensitivity by TXNRD1 in pancreatic cancer cells
Authors: Cai Luke L. , Ruberto Richard A. , Ryan Matthew J. , Eaton John K. , Schreiber Stuart L. , Viswanathan Vasanthi S. 
Published: June 2020

AbstractThe selenoprotein thioredoxin reductase 1 (TXNRD1) plays a central role in ameliorating oxidative stress. Inhibition of TXNRD1 has been explored as a means of killing cancer cells that are thought to develop an enhanced reliance on such antioxidant proteins. In the context of ferroptosis, a non-apoptotic form of oxidative cell death, TXNRD1 has been proposed to cooperate with the phospholipid hydroperoxidase enzyme glutathione peroxidase 4 (GPX4) to protect cells from the lethal accumulation of lipid peroxides. Here, we report our unexpected finding that in pancreatic cancer cells, CRISPR–Cas9-mediated loss of TXNRD1 confers protection from ferroptosis induced by small-molecule inhibition of GPX4. Insights stemming from mechanistic interrogation of this phenomenon suggest that loss of TXNRD1 results in increased levels of GPX4 protein, potentially by influencing availability of selenocysteine, a scarce amino acid required by both proteins for proper synthesis and function. Increased abundance of GPX4 protein, in turn, protects cells from the effects of small-molecule GPX4 inhibition. These findings implicate selenoprotein regulation in governing ferroptosis sensitivity. Furthermore, by delineating a relationship between GPX4 and TXNRD1 contrary to that observed in numerous other settings, our discoveries underscore the context-specific nature of ferroptosis circuitry and its modulators.
More than noise: Context-dependant luminance contrast discrimination in a coral reef fish (Rhinecanthus aculeatus)
Authors: van den Berg Cedric P. , Hollenkamp Michelle , Mitchell Laurie J. , Watson Erin J. , Green Naomi F. , Marshall N. Justin , Cheney Karen L. 
Published: June 2020

AbstractAchromatic (luminance) vision is used by animals to perceive motion, pattern, space and texture. Luminance contrast sensitivity thresholds are often poorly characterised for individual species and are applied across a diverse range of perceptual contexts using over-simplified assumptions of an animal’s visual system. Such thresholds are often estimated using the Receptor Noise Limited model (RNL) using quantum catch values and estimated noise levels of photoreceptors. However, the suitability of the RNL model to describe luminance contrast perception remains poorly tested.Here, we investigated context-dependent luminance discrimination using triggerfish (Rhinecanthus aculeatus)presented with large achromatic stimuli (spots) against uniform achromatic backgrounds of varying absolute and relative contrasts. ‘Dark’ and ‘bright’ spots were presented against relatively dark and bright backgrounds. We found significant differences in luminance discrimination thresholds across treatments. When measured using Michelson contrast, thresholds for bright spots on a bright background were significantly higher than for other scenarios, and the lowest threshold was found when dark spots were presented on dark backgrounds. Thresholds expressed in Weber contrast revealed increased contrast sensitivity for stimuli darker than their backgrounds, which is consistent with the literature. The RNL model was unable to estimate threshold scaling across scenarios as predicted by the Weber-Fechner law, highlighting limitations in the current use of the RNL model to quantify luminance contrast perception. Our study confirms that luminance contrast discrimination thresholds are context-dependent and should therefore be interpreted with caution.
Harvest and Culture of Porcine Adipose-Derived Mesenchymal Stem Cells for Autologous Transplantation
Authors: Sharma Ayushman , Dietz Allan B. 
Published: June 2020

AbstractImportanceTransplantation of adipose-derived (mesenchymal) stem cells (ADSCs) are currently under investigation for numerous novel regenerative cell therapies of the head, neck and periphery. Critical to the development of these techniques is the availability of large-animal models that can be used to test the safety and efficacy of these approaches in a manner that provides source material (in this case MSC) analogous to those developed in humans.ObjectiveTo describe the surgical technique and laboratory procedures for harvesting and isolating porcine ADSCs that are functionally equivalent to human ADSCs without sacrificing the donor animal.MethodsThe reagents and methods used in the porcine model described were purposefully focused to be able to be sufficiently analogous to those used in humans such that data developed using these techniques should support the use of porcine models for regulatory submissions.ResultsWe describe a method and confirm the activity of functionally analogous adipose derived porcine MSC. Two conditions were critical to move gain analogous performance: the cells needed to be incubated at porcine body temperature (39°C) and the cells were more sensitive to initial plating densities with plating densities of 20,000 cells/cm2being optimal.DiscussionThis approach will allow reproducible and predictable use of an autologous large-animal model for testing AMDSC therapies.
Intra-session test-retest reliability of functional connectivity in infants
Authors: Wang Yun , Hinds Walter , Duarte Cristiane S , Lee Seonjoo , Monk Catherine , Wall Melanie , Canino Glorisa , Milani Ana Carolina C. , Jackowski Andrea , Mamin Marina Griorgi , Foerster Bernd U. , Gingrich Jay , Weissman Myrna M , Peterson Bradley S. , Semanek David , Perez Edna Acosta , Labat Eduardo , Torres Ioannisely Berrios , Da Silva Ivaldo , Parente Camila , Abdala Nitamar , Posner Jonathan 
Published: June 2020

AbstractResting functional MRI studies of the infant brain are increasingly becoming an important tool in developmental neuroscience. Whereas the test-retest reliability of functional connectivity (FC) measures derived from resting fMRI data have been characterized in the adult and child brain, similar assessments have not been conducted in infants. In this study, we examined the intra-session test-retest reliability of FC measures from 119 infant brain MRI scans from four neurodevelopmental studies. We investigated edge-level and subject-level reliability within one MRI session (between and within runs) measured by the Intraclass correlation coefficient (ICC). First, using an atlas-based approach, we examined whole-brain connectivity as well as connectivity within two common resting fMRI networks – the default mode network (DMN) and the sensorimotor network (SMN). Second, we examined the influence of run duration, study site, and scanning manufacturer (e.g., Philips and General Electric) on ICCs. Lastly, we tested spatial similarity using the Jaccard Index from networks derived from independent component analysis (ICA). Consistent with resting fMRI studies from adults, our findings indicated poor edge-level reliability (ICC = 0.14 - 0.18), but moderate-to-good subject-level intra-session reliability for whole-brain, DMN, and SMN connectivity (ICC = 0.40 - 0.78). We also found significant effects of run duration, site, and scanning manufacturer on reliability estimates. Some ICA-derived networks showed strong spatial reproducibility (e.g., DMN, SMN, and Visual Network), and were labelled based on their spatial similarity to analogous networks measured in adults. These networks were reproducibly found across different study studies. However, other ICA-networks (e.g. Executive Control Network) did not show strong spatial reproducibility, suggesting that the reliability and/or maturational course of functional connectivity may vary by network. In sum, our findings suggest that developmental scientist may be on safe ground examining the functional organization of some major neural networks (e.g. DMN and SMN), but judicious interpretation of functional connectivity is essential to its ongoing success.HighlightsInfant functional connectivity (FC) shows poor edge-level reliability (ICCs)However, subject-level infant FC estimates show good-to-excellent ICCsSpatial reproducibility is better for some resting networks (DMN, SMN) than others (ECN)Reliability estimates differ across study site and MRI scannerConclusion - Infant FC can be a reliable measurement, but judicious use is needed
A multi-omic integrative scheme characterizes tissues of action at loci associated with type 2 diabetes
Authors: Torres Jason M. , Abdalla Moustafa , Payne Anthony , Fernandez-Tajes Juan , Thurner Matthias , Nylander Vibe , Gloyn Anna L. , Mahajan Anubha , McCarthy Mark I. 
Published: June 2020

AbstractResolving the molecular processes that mediate genetic risk remains a challenge as most disease-associated variants are non-coding and functional and bioinformatic characterization of these signals requires knowledge of the specific tissues and cell-types in which they operate. To address this challenge, we developed a framework for integrating tissue-specific gene expression and epigenomic maps (primarily from tissues involved in insulin secretion and action) to obtaintissue-of-action(TOA) scores for each association signal by systematically partitioning posterior probabilities from Bayesian fine-mapping. We applied this scheme to credible set variants for 380 association signals from a recent GWAS meta-analysis of type 2 diabetes (T2D) in Europeans. The resulting tissue profiles underscored a predominant role for pancreatic islets and, to a lesser extent, subcutaneous adipose and liver, that was largely attributable to enhancer elements and transcribed regions, particularly among signals with greater fine-mapping resolution. We incorporated resulting TOA scores into a rule-based classifier, and validated the tissue assignments through comparison with data fromcis-eQTL enrichment, functional fine-mapping, RNA co-expression, and patterns of physiological association. In addition to implicating signals with a single tissue-of-action, we also found evidence for signals with shared effects in multiple tissues as well as distinct tissue profiles between independent signals within heterogeneous loci. Lastly, we demonstrated that TOA scores can be directly coupled with eQTL colocalization to further resolve effector transcripts at T2D signals. This framework guides mechanistic inference by directing functional validation studies to the most relevant tissues and can gain power as fine-mapping resolution and cell-specific annotations become richer. This method is generalizable to all complex traits with relevant annotation data and is made available as an R package.
Application of Surgical Lead Management and Reconfigurable Coil Technology to Reduce RF Heating of DBS Implants during MRI at 3T Under Variant Body Compositions
Authors: Bhusal Bhumi , Elahi Behzad , Keil Boris , Rosenow Joshua , Kazemivalipour Ehsan , Golestanirad Laleh 
Published: June 2020

AbstractPatients with active implants such as deep brain stimulation (DBS) devices, have limited access to magnetic resonance imaging (MRI) due to risks of RF heating. With an aging population, the prevalence of neurodegenerative and vascular disease increases; and so does the indication for MRI exams in patients with such implants. In response to this growing need for MRI, many groups have investigated strategies to mitigate the RF heating of the implants. These efforts, however, have relied either on simulations with homogenous body models or simplified phantom experiments (box shaped phantom with single tissue). It is well established, however, that the shape and heterogeneity of human body affects the distribution of MRI electric fields, which by proxy, alters the RF heating of an implant inside the body. In this contribution, we applied numerical simulations and phantom experiments to examine the effectiveness of RF heating mitigation strategies under variant patient body compositions, focusing on two recently proposed techniques: (a) surgical modification of DBS lead trajectories inside the body, and (b) use of a patient-adjustable reconfigurable MRI coil, both aiming to reduce the coupling of implanted leads and MRI electric fields. Our results demonstrated that both techniques perform well under variant body compositions.
Model-driven promoter strength prediction based on a fine-tuned synthetic promoter library inEscherichia coli
Authors: Zhao Mei , Zhou Shenghu , Wu Longtao , Deng Yu 
Published: June 2020

AbstractPromoters are one of the most critical regulatory elements controlling metabolic pathways. However, in recent years, researchers have simply perfected promoter strength, but ignored the relationship between the internal sequences and promoter strength. In this context, we constructed and characterized a mutant promoter library of Ptrcthrough dozens of mutation-construction-screening-characterization engineering cycles. After excluding invalid mutation sites, we established a synthetic promoter library, which consisted of 3665 different variants, displaying an intensity range of more than two orders of magnitude. The strongest variant was 1.52-fold stronger than a 1 mM isopropyl-β-D-thiogalactoside driven PT7promoter. Our synthetic promoter library exhibited superior applicability when expressing different reporters, in both plasmids and the genome. Different machine learning models were built and optimized to explore relationships between the promoter sequences and transcriptional strength. Finally, our XgBoost model exhibited optimal performance, and we utilized this approach to precisely predict the strength of artificially designed promoter sequences. Our work provides a powerful platform that enables the predictable tuning of promoters to achieve the optimal transcriptional strength.
Structure and allosteric regulation of human IDH3 holoenzyme
Authors: Sun Pengkai , Liu Yan , Ma Tengfei , Ding Jianping 
Published: June 2020

AbstractHuman NAD-dependent isocitrate dehydrogenase or IDH3 catalyzes the decarboxylation of isocitrate into α-ketoglutarate in the TCA cycle. We here report the structure of the IDH3 holoenzyme, in which the αβ and αγ heterodimers assemble the α2βγ heterotetramer via their clasp domains, and two α2βγ heterotetramers assemble the (α2βγ)2heterooctamer via the β and γ subunits. The functional roles of the key residues involved in the assembly and allosteric regulation are validated by mutagenesis and kinetic studies. The allosteric site plays an important role but the pseudo allosteric site plays no role in the allosteric activation; the activation signal from the allosteric site is transmitted to the active sites of both heterodimers via the clasp domains; and the N-terminus of the γ subunit plays a critical role in the formation and function of the holoenzyme. These findings reveal the molecular mechanism of the assembly and allosteric regulation of human IDH3 holoenzyme.
Draft Genome Sequences of 10 Strains ofPseudomonas syringaepv.actinidiaeBiovar 1: A Major Kiwifruit Bacterial Canker Pathogen in Japan
Authors: Fujikawa Takashi , Hatomi Hiroe , Sawada Hiroyuki 
Published: June 2020

AbstractSeveral groups (biovars) of the kiwifruit bacterial canker pathogen,Pseudomonas syringaepv.actinidiae, are found in Japan. Here, we sequenced and compared the 10 genomes of biovar 1, the major group in Japan, which is known as the phaseolotoxin producer.The kiwifruit bacterial canker pathogen,Pseudomonas syringaepv.actinidiae(Psa), was first described in Japan in 1989 (1). Subsequently, Psa was found in other kiwifruit-producing countries (2). Based on comparative analyses (2–4), Psa was categorized into several groups (biovars). The first Japanese group was named biovar 1 (Psa1), which was also later found in Italy and Korea. This biovar produces phaseolotoxin (2), a phytotoxin that inhibits arginine biosynthesis in host plants and results in bacterial canker symptom development. On the Psa1 chromosome, a large number of genes involved in phaseolotoxin biosynthesis are accumulated in an approximately 23 kb region (argK-toxcluster), which is contained in an exogenous genomic island (toxisland) that Psa1 acquired in the past (2). However, some Psa1 strains found in Ehime Prefecture, Japan (the Ehime isolates) do not produce phaseolotoxin, although they seem to possess theargK-toxcluster (5). On the other hand, several Psa1 strains preserved in the NARO Genebank (https://www.gene.affrc.go.jp/index_en.php) may lack this cluster (2). Here, we selected 10 strains (Table 1) that represent Psa1 diversity and conducted comparative genome analyses.