bluuebunny/crossref_metadata_2025_split huggingface dataset:
Freeze-dried plasma for major trauma – Systematic review and meta-analysis
Authors: Mok Garrick , Hoang Richard , Khan Montaha Wajid , Pannell Dylan , Peng Henry , Tien Homer , Nathens Avery , Callum Jeannie , Karkouti Keyvan , Beckett Andrew , da Luz Luis Teodoro 
Published: November 2020

BACKGROUND
Treatment of acute trauma coagulopathy has shifted toward rapid replacement of coagulation factors with frozen plasma (FP). There are logistic difficulties in providing FP. Freeze-dried plasma (FDP) may have logistical advantages including easier storage and rapid preparation time. This review assesses the feasibility, efficacy, and safety of FDP in trauma.

STUDY DESIGN AND METHODS
Studies were searched from Medline, Embase, Cochrane Controlled Trials Register, ClinicalTrials.gov, and Google Scholar. Observational and randomized controlled trials (RCTs) assessing FDP use in trauma were included. Trauma animal models addressing FDP use were also included. Bias was assessed using validated tools. Primary outcome was efficacy, and secondary outcomes were feasibility and safety. Meta-analyses were conducted using random-effect models. Evidence was graded using Grading of Recommendations Assessment, Development, and Evaluation profile.

RESULTS
Twelve human studies (RCT, 1; observational, 11) and 15 animal studies were included. Overall, studies demonstrated moderate risk of bias. Data from two studies (n = 119) were combined for meta-analyses for mortality and transfusion of allogeneic blood products (ABPs). For both outcomes, no difference was identified. For mortality, pooled odds ratio was 0.66 (95% confidence interval, 0.29–1.49), with I
2 = 0%. Use of FDP is feasible, and no adverse events were reported. Animal data suggest similar results for coagulation and anti-inflammatory profiles for FP and FDP.

CONCLUSION
Human data assessing FDP use in trauma report no difference in mortality and transfusion of ABPs in patients receiving FDP compared with FP. Data from animal trauma studies report no difference in coagulation factor and anti-inflammatory profiles between FP and FDP. Results should be interpreted with caution because most studies were observational and have heterogeneous population (military and civilian trauma) and a moderate risk of bias. Well-designed prospective observational studies or, preferentially, RCTs are warranted to answer FDP’s effect on laboratory (coagulation factor levels), transfusion (number of ABPs), and clinical outcomes (organ dysfunction, length of stay, and mortality).

LEVEL OF EVIDENCE
Systematic review and meta-analysis, level IV.
The m6A methyltransferase METTL3 promotes LPS-induced microglia inflammation through TRAF6/NF-κB pathway
Authors: Wen Linbao , Sun Wei , Xia Dayong , Wang Yanming , Li Junpeng , Yang Song 
Published: November 2020

Objectives
Microglia are the main effectors in the inflammatory process of the central nervous system. Once overactivated, microglia may release pro-inflammatory cytokines (IL-1β, IL-6, TNF-α and IL-18, etc.) and accelerate neurodegeneration. Here, we aimed to explore the mechanism of how m6A methyltransferase METTL3 affects the inflammatory response of microglia, appropriately inhibiting the overactivation of microglia.

Materials and methods
Lipopolysaccharide (LPS) was used to construct a cellular inflammation model in vitro. To evaluate the expression of METTL3 and inflammatory cytokines (IL-1β, IL-6, TNF-α and IL-18) in cells, RT-PCR and ELISA were carried out. The related protein (TRAF6, NF-κB and I-κB) expression was examined adopting Western blot. Dot blot experiment was used to assess the effect of regulating METTL3 on the m6A level. Methylated RNA immunoprecipitation reaction was used to measure the effect of METTL3 on the m6A level of TRAF6 mRNA 3′-UTR. The co-immunoprecipitation experiment (IP) proved that METTL3 combines with TRAF6.

Results
In LPS-mediated microglial inflammation, METTL3 expression was increased, and the expression of inflammatory cytokines (IL-1β, IL-6, TNF-α and IL-18) and inflammatory proteins (TRAF6 and NF-κB) were upregulated. METTL3 level was positively correlated with TRAF6, and the two proteins could bind to each other. Overexpression of METTL3 promoted the activation of the TRAF6-NF-κB pathway in an m6A-dependent manner, and inhibiting NF-κB attenuated METTL3-mediated microglial activation.

Conclusion
METTL3 promotes LPS-induced microglial inflammation by activating the TRAF6-NF-κB pathway.
Atmospheric chemistry on Uranus and Neptune
Authors: Moses J. I. , Cavalié T. , Fletcher L. N. , Roman M. T. 
Published: November 2020

Comparatively little is known about atmospheric chemistry on Uranus and Neptune, because remote spectral observations of these cold, distant ‘Ice Giants’ are challenging, and each planet has only been visited by a single spacecraft during brief flybys in the 1980s. Thermochemical equilibrium is expected to control the composition in the deeper, hotter regions of the atmosphere on both planets, but disequilibrium chemical processes such as transport-induced quenching and photochemistry alter the composition in the upper atmospheric regions that can be probed remotely. Surprising disparities in the abundance of disequilibrium chemical products between the two planets point to significant differences in atmospheric transport. The atmospheric composition of Uranus and Neptune can provide critical clues for unravelling details of planet formation and evolution, but only if it is fully understood how and why atmospheric constituents vary in a three-dimensional sense and how material coming in from outside the planet affects observed abundances. Future mission planning should take into account the key outstanding questions that remain unanswered about atmospheric chemistry on Uranus and Neptune, particularly those questions that pertain to planet formation and evolution, and those that address the complex, coupled atmospheric processes that operate on Ice Giants within our solar system and beyond.This article is part of a discussion meeting issue ‘Future exploration of ice giant systems’.
Auroral emissions from Uranus and Neptune
Authors: Lamy L. 
Published: November 2020

Uranus and Neptune possess highly tilted/offset magnetic fields whose interaction with the solar wind shapes unique twin asymmetric, highly dynamical, magnetospheres. These radiate complex auroral emissions, both reminiscent of those observed at the other planets and unique to the ice giants, which have been detected at radio and ultraviolet (UV) wavelengths to date. Our current knowledge of these radiations, which probe fundamental planetary properties (magnetic field, rotation period, magnetospheric processes, etc.), still mostly relies on Voyager 2 radio, UV andin situmeasurements, when the spacecraft flew by each planet in the 1980s. These pioneering observations were, however, limited in time and sampled specific solar wind/magnetosphere configurations, which significantly vary at various timescales down to a fraction of a planetary rotation. Since then, despite repeated Earth-based observations at similar and other wavelengths, only the Uranian UV aurorae have been re-observed at scarce occasions by the Hubble Space Telescope. These observations revealed auroral features radically different from those seen by Voyager 2, diagnosing yet another solar wind/magnetosphere configuration. Perspectives for the in-depth study of the Uranian and Neptunian auroral processes, with implications for exoplanets, include follow-up remote Earth-based observations and future orbital exploration of one or both ice giant planetary systems.This article is part of a discussion meeting issue ‘Future exploration of ice giant systems’.
Lessons learned from (and since) the Voyager 2 flybys of Uranus and Neptune
Authors: Hammel Heidi B. 
Published: November 2020

More than 30 years have passed since the Voyager 2 flybys of Uranus and Neptune. This paper outlines a range of lessons learned from Voyager, broadly grouped into ‘process, planning and people.’ In terms of process, we must be open to new concepts, whether new instrument technologies, new propulsion systems or operational modes. Examples from recent decades that could open new vistas in the exploration of the deep outer Solar System include the Cassini Resource Exchange and the ‘sleep’ mode from the New Horizons mission. Planning is crucial: mission gaps that last over three decades leave much scope for evolution both in mission development and in the targets themselves. The science is covered in other papers in this issue, but this paper addresses the structure of the US Planetary Decadal Surveys, with a specific urging to move from a ‘destination-based’ organization to a structure based on fundamental science. Coordination of distinct and divergent international planning timelines brings both challenges and opportunity. Complexity in the funding and political processes is amplified when multiple structures must be navigated; but the science is enriched by the diversity of international perspectives, as were represented at the Ice Giant discussion meeting that motivated this review. Finally, the paper turns to people: with generational-length gaps between missions, continuity in knowledge and skills requires careful attention to people. Lessons for the next generation of voyagers include: how to lead and inspire; how to develop the perspective to see their missions through decades-long development phases; and cultivation of strategic thinking, altruism and above all, patience.
This article is part of a discussion meeting issue ‘Future exploration of ice giant systems’.
Genetic variants are identified to increase risk of COVID-19 related mortality from UK Biobank data
Authors: Hu Jianchang , Li Cai , Wang Shiying , Li Ting , Zhang Heping 
Published: November 2020

AbstractBackgroundThe severity of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly heterogenous. Studies have reported that males and some ethnic groups are at increased risk of death from COVID-19, which implies that individual risk of death might be influenced by host genetic factors.MethodsIn this project, we consider the mortality as the trait of interest and perform a genome-wide association study (GWAS) of data for 1,778 infected cases (445 deaths, 25.03%) distributed by the UK Biobank. Traditional GWAS failed to identify any genome-wide significant genetic variants from this dataset. To enhance the power of GWAS and account for possible multi-loci interactions, we adopt the concept of super-variant for the detection of genetic factors. A discovery-validation procedure is used for verifying the potential associations.ResultsWe find 8 super-variants that are consistently identified across multiple replications as susceptibility loci for COVID-19 mortality. The identified risk factors on Chromosomes 2, 6, 7, 8, 10, 16, and 17 contain genetic variants and genes related to cilia dysfunctions (DNAH7andCLUAP1), cardiovascular diseases (DESandSPEG), thromboembolic disease (STXBP5), mitochondrial dysfunctions (TOMM7), and innate immune system (WSB1). It is noteworthy thatDNAH7has been reported recently as the most downregulated gene after infecting human bronchial epithelial cells with SARS-CoV2.ConclusionsEight genetic variants are identified to significantly increase risk of COVID-19 mortality among the patients with white British ancestry. These findings may provide timely evidence and clues for better understanding the molecular pathogenesis of COVID-19 and genetic basis of heterogeneous susceptibility, with potential impact on new therapeutic options.
A novel anti-inflammatory treatment for bradykinin-induced sore throat or pharyngitis
Authors: Leyva-Grado Victor , Pugach Pavel , Latefi Nazlie 
Published: November 2020

AbstractBackgroundOften thought of as a minor health concern, sore throat or pharyngitis is an important public health issue. It is one of the most common symptoms of upper respiratory diseases including COVID-19 and is a leading cause of physician visits and antibiotic prescriptions. However, few over the counter medications are proven to heal sore throat inflammation.MethodsAdenocarcinomic human alveolar basal epithelial cells (A549 cells) and three dimensional organotypic human respiratory tissues were used to study inflammation and various treatment effects on respiratory epithelia. The cells and tissues were studied both in the presence and absence of bradykinin, one of the first inflammatory mediators of pharyngitis. Inflammation was measured by analyzing levels of prostaglandin E2 (PGE2), interleukin 8 (IL-8), and leukotriene B4 (LTB4), transepithelial electrical resistance (TEER), and lactate dehydrogenase (LDH) release. Tissue morphology was analyzed by immunohistochemistry.ResultsIn studying pharyngitis using organotypic human respiratory tissue stimulated with bradykinin, we saw an increase in prostaglandin E2 (PGE2) and interleukin-8 (IL-8) in response to bradykinin. Acetyl salicylic acid (ASA), a non-specific COX inhibitor, was able to mitigate a bradykinin-induced increase in PGE2 in our studies. However, ASA was inflammatory above its therapeutic window, increasing levels of PGE2 and IL-8 above those seen with bradykinin stimulation alone. We describe a novel, scientifically validated treatment for sore throat, that contains a low dose of aspirin and other anti-inflammatory ingredients.ConclusionThis study elucidates the complex mechanisms involved in healing pharyngitis, an inflammatory condition of the upper respiratory epithelia. An ASA-based formula (Biovanta) mitigated bradykinin-induced inflammation more strongly than ASA alone in organotypic human respiratory tissues. Surprisingly, we found that many of the most common over the counter sore throat therapies exacerbate inflammation and IL-8 in organotypic human respiratory tissues, suggesting these common treatments may increase the likelihood of further respiratory complications.Competing interest statementThis study was funded entirely by Applied Biological Laboratories, a private company that owns the Biovanta™ product. Some studies were conducted by third parties in a blind format, as indicated. All other experiments were performed at Applied Biological Laboratories’ research facility located at the SUNY Downstate Biotechnology Incubator, a part of StartUP NY. All of the authors were employees of Applied Biological Laboratories at the time the experiments were performed.
Quantitative genetic basis of floral design in a natural plant population
Authors: Zhou Juannan , Fenster Charles B. , Reynolds Richard J. 
Published: November 2020

AbstractThe amount of genetic variation of floral traits and the degree to which they are genetically correlated are important parameters for the study of plant evolution. Estimates of these parameters can reveal the effect of historical selection relative to neutral processes such as mutation and drift, and allow us to predict the short-term evolutionary trajectory of a population under various selective regimes. Here, we assess the heritability and genetic correlation of the floral design of a native N. American tetraploid plant,Silene stellata(Caryophyllaceae), in a natural population. Specifically, we use a linear mixed model to estimate the genetic parameters based on a genealogy reconstructed from highly variable molecular markers. Overall, we found significant heritabilities in five out of nine studied traits. The level of heritability was intermediate (0.027 – 0.441). Interestingly, the floral trait showing the highest level of genetic variation was previously shown to be under strong sexually conflicting selection, which may serve as a mechanism for maintaining the observed genetic variation. Additionally, we also found prevalent positive genetic correlations between floral traits. Our results suggest thatS. stellatais capable of responding to phenotypic selection on its floral design, while the abundant positive genetic correlations could also constrain the evolutionary trajectories to certain directions. Furthermore, this study demonstrates the utility and feasibility of marker-based approaches for estimating genetic parameters in natural populations.
χ-separation: Magnetic susceptibility source separation toward iron and myelin mapping in the brain
Authors: Shin Hyeong-Geol , Lee Jingu , Yun Young Hyun , Yoo Seong Ho , Jang Jinhee , Oh Se-Hong , Nam Yoonho , Jung Sehoon , Kim Sunhye , Fukunaga Masaki , Kim Woojun , Choi Hyung Jin , Lee Jongho 
Published: November 2020

AbstractObtaining a histological fingerprint from thein-vivobrain has been a long-standing target of magnetic resonance imaging (MRI). In particular, non-invasive imaging of iron and myelin, which are involved in normal brain functions and are histopathological hallmarks in neurodegenerative diseases, has practical utilities in neuroscience and medicine. Here, we propose a biophysical model that describes the individual contribution of paramagnetic (e.g., iron) and diamagnetic (e.g., myelin) susceptibility sources to the frequency shift and transverse relaxation of MRI signals. Using this model, we develop a method,χ-separation, that generates the voxel-wise distributions of the two sources. The method is validated using computer simulation and phantom experiments, and applied toex-vivoandin-vivobrains. The results delineate the well-known histological features of iron and myelin in the specimen, healthy volunteers, and multiple sclerosis patients. This new technology may serve as a practical tool for exploring the microstructural information of the brain.
Identification of cell-type-specific marker genes from co-expression patterns in tissue samples
Authors: Qiu Yixuan , Wang Jiebiao , Lei Jing , Roeder Kathryn 
Published: November 2020

AbstractMotivationMarker genes, defined as genes that are expressed primarily in a single cell type, can be identified from the single cell transcriptome; however, such data are not always available for the many uses of marker genes, such as deconvolution of bulk tissue. Marker genes for a cell type, however, are highly correlated in bulk data, because their expression levels depend primarily on the proportion of that cell type in the samples. Therefore, when many tissue samples are analyzed, it is possible to identify these marker genes from the correlation pattern.ResultsTo capitalize on this pattern, we develop a new algorithm to detect marker genes by combining published information about likely marker genes with bulk transcriptome data in the form of a semi-supervised algorithm. The algorithm then exploits the correlation structure of the bulk data to refine the published marker genes by adding or removing genes from the list.Availability and implementationWe implement this method as an R package markerpen, hosted onhttps://github.com/yixuan/markerpen.Contactroeder@andrew.cmu.edu
Dual clathrin and adhesion signaling systems regulate growth factor receptor activation
Authors: Alfonzo-Mendez Marco A. , Sochacki Kem A. , Strub Marie-Paule , Taraska Justin W. 
Published: November 2020

ABSTRACTThe crosstalk between growth factor and adhesion receptors is key for cell growth and migration. In pathological settings, these receptors are drivers of cancer. Yet, how growth and adhesion signals are spatially organized and integrated is poorly understood. Here we use quantitative fluorescence and electron microscopy to reveal a mechanism where flat clathrin lattices partition and activate growth factor signals via a coordinated response that involves crosstalk between epidermal growth factor receptor (EGFR) and the adhesion receptor β5-integrin. We show that ligand-activated EGFR, Grb2, Src, and β5-integrin are captured by clathrin coated-structures at the plasma membrane. Clathrin structures dramatically grow in response to ligand activation into large flat plaques and provide a signaling platform that link EGFR and β5-integrin through Src-mediated phosphorylation. Disrupting this EGFR/Src/β5-integrin axis prevents both clathrin plaque growth and receptor signaling. Our study reveals a reciprocal regulation of clathrin lattices and two different receptor systems to enhance cell growth factor signaling. These findings have broad implications for the control of growth factor receptors, mechanotransduction, and endocytosis.
Exosomal melanotransferrin as a potential biomarker for metastatic melanoma
Authors: Bonhoure Anne , Henry Laurent , Morille Marie , Aissaoui Nesrine , Bellot Gaëtan , Stoebner Pierre-Emmanuel , Vidal Michel 
Published: November 2020

AbstractCutaneous melanoma is the most lethal type of skin cancer. Early detection is crucial to improve the outcome of melanoma patients. The identification of noninvasive prognostic biomarkers for the follow-up of melanoma patients is still in demand for clinical use. We show here that exosomal melanotransferrin (MTf) fulfils the biomarker characteristics required to meet this demand. MTf is typically overexpressed in melanoma cells compared to other cell types – including cancer cells – and is efficiently sorted and secreted with nanovesicles, or so-called exosomes, due to its membrane-anchoring by a glycosylphosphatidylinositol. MTf is exposed on the surface of exosomes and is accessible for antibody recognition. An ELISA was set-up to quantify MTf after immobilization of nanovesicles through the exosomal constituent tetraspanins CD63. MTf was detected using low number of exosomes purified from melanoma cell line cultures, and MTf detection was abolished by phosphatidylinositol-specific phospholipase C (PI-PLC) treatment. This exosomal MTf ELISA was able to discriminate an equal number of assayed exosomes purified from two different melanoma cell lines (A-375 vs SK-MEL-28). Moreover, plasma samples from patients with melanoma and noncancer disease were assayed using this ELISA and exosomal MTf was validated as a potential melanoma biomarker.
Control techniques for enhancing performance of PV system under dynamic conditions
Authors: Ehtesham Md , Jamil Majid 
Published: November 2020

Purpose
The purpose of this paper is to focus on two major areas of concern for the Photovoltaic (PV) system, i.e. power quality and maximum power point tracking (MPPT). Novel control strategies have been proposed for both these issues, and their respective superiorities over the existing techniques have been established. On the other hand, as far as MPPT is concerned, two limitations are found in the available techniques. One is the inability of effective MPPT in dynamic conditions where the environmental parameters changes very rapidly. Second one is the ineffective tracking of global maxima under partial shading conditions.

Design/methodology/approach
Here, modified Kalman filtering approach has been applied for estimating the reference current of active power filter, incorporated for power quality improvement. The proposed Kalman algorithm introduces a weighted matrix, which advances the estimated values of state variables. This paper presents a simple and enhanced model-based (MB) MPPT algorithm that has the capability of tracking MPPT effectively in both these working conditions. The proposed MB algorithm uses the mathematical modelling, and based on precised estimation of parameters, it pre-determines the MPP analytically.

Findings
It has been tested successfully for dynamic variations of insolation, temperature and partial shading, where all these three parameters are rigorously varied over the full scale of practical values. The results have been also investigated experimentally and compared with the simulated one. A close matching of both the results has been shown through the plots, which validates the effectiveness of proposed algorithms.

Originality/value
This research paper is part of the original research work carried out in Lab. Simulated results are obtained in MATLAB/Simulink platform, whereas these are further validated experimentally on 2-KW panel constituted with all types of commercial products, namely, mono, poly and thin-film.