bluuebunny/crossref_metadata_2025_split huggingface dataset:
A New Framework to Explain Changes in Io's Footprint Tail Electron Fluxes
Authors: Szalay J. R. , Allegrini F. , Bagenal F. , Bolton S. J. , Bonfond B. , Clark G. , Connerney J. E. P. , Ebert R. W. , Hue V. , McComas D. J. , Saur J. , Sulaiman A. H. , Wilson R. J. 
Published: September 2020

AbstractWe analyze precipitating electron fluxes connected to 18 crossings of Io's footprint tail aurora, over altitudes of 0.15 to 1.1 Jovian radii (RJ). The strength of precipitating electron fluxes is dominantly organized by “Io‐Alfvén tail distance,” the angle along Io's orbit between Io and an Alfvén wave trajectory connected to the tail aurora. These fluxes best fit an exponential as a function of down‐tail extent with an e‐folding distance of 21°. The acceleration region altitude likely increases down‐tail, and the majority of parallel electron acceleration sustaining the tail aurora occurs above 1 RJ in altitude. We do not find a correlation between the tail fluxes and the power of the initial Alfvén wave launched from Io. Finally, Juno has likely transited Io's Main Alfvén Wing fluxtube, observing a characteristically distinct signature with precipitating electron fluxes ~600 mW/m2 and an acceleration region extending as low as 0.4 RJ in altitude.
Large Variations in Volcanic Aerosol Forcing Efficiency Due to Eruption Source Parameters and Rapid Adjustments
Authors: Marshall Lauren R. , Smith Christopher J. , Forster Piers M. , Aubry Thomas J. , Andrews Timothy , Schmidt Anja 
Published: September 2020

AbstractThe relationship between volcanic stratospheric aerosol optical depth (SAOD) and volcanic radiative forcing is key for quantifying volcanic climate impacts. In their Fifth Assessment Report, the Intergovernmental Panel on Climate Change used one scaling factor between volcanic SAOD and volcanic forcing based on climate model simulations of the 1991 Mt. Pinatubo eruption, which may not be appropriate for all eruptions. Using a large ensemble of aerosol‐chemistry‐climate simulations of eruptions with different sulfur dioxide emissions, latitudes, emission altitudes, and seasons, we find that the effective radiative forcing (ERF) is on average 20% less than the instantaneous radiative forcing, predominantly due to a positive shortwave cloud adjustment. In our model, the volcanic SAOD‐ERF relationship is non‐unique and varies widely depending on time since an eruption, eruption latitude, and season due to differences in aerosol dispersion and incoming solar radiation. Our revised SAOD‐ERF relationships suggest that volcanic forcing has been previously overestimated.
Artificial intelligence enhanced two-dimensional nanoscale nuclear magnetic resonance spectroscopy
Authors: Kong Xi , Zhou Leixin , Li Zhijie , Yang Zhiping , Qiu Bensheng , Wu Xiaodong , Shi Fazhan , Du Jiangfeng 
Published: September 2020

AbstractTwo-dimensional nuclear magnetic resonance (NMR) is indispensable to molecule structure determination. Nitrogen-vacancy center in diamond has been proposed and developed as an outstanding quantum sensor to realize NMR in nanoscale or even single molecule. However, like conventional multi-dimensional NMR, a more efficient data accumulation and processing method is necessary to realize applicable two-dimensional (2D) nanoscale NMR with a high spatial resolution nitrogen-vacancy sensor. Deep learning is an artificial algorithm, which mimics the network of neurons of human brain, has been demonstrated superb capability in pattern identifying and noise canceling. Here we report a method, combining deep learning and sparse matrix completion, to speed up 2D nanoscale NMR spectroscopy. The signal-to-noise ratio is enhanced by 5.7 ± 1.3 dB in 10% sampling coverage by an artificial intelligence protocol on 2D nanoscale NMR of a single nuclear spin cluster. The artificial intelligence algorithm enhanced 2D nanoscale NMR protocol intrinsically suppresses the observation noise and thus improves sensitivity.
Structural models of human ACE2 variants with SARS-CoV-2 Spike protein for structure-based drug design
Authors: Sorokina Marija , M. C. Teixeira João , Barrera-Vilarmau Susana , Paschke Reinhard , Papasotiriou Ioannis , Rodrigues João P. G. L. M. , Kastritis Panagiotis L. 
Published: September 2020

AbstractEmergence of coronaviruses poses a threat to global health and economy. The current outbreak of SARS-CoV-2 has infected more than 28,000,000 people and killed more than 915,000. To date, there is no treatment for coronavirus infections, making the development of therapies to prevent future epidemics of paramount importance. To this end, we collected information regarding naturally-occurring variants of the Angiotensin-converting enzyme 2 (ACE2), an epithelial receptor that both SARS-CoV and SARS-CoV-2 use to enter the host cells. We built 242 structural models of variants of human ACE2 bound to the receptor binding domain (RBD) of the SARS-CoV-2 surface spike glycoprotein (S protein) and refined their interfaces with HADDOCK. Our dataset includes 140 variants of human ACE2 representing missense mutations found in genome-wide studies, 39 mutants with reported effects on the recognition of the RBD, and 63 predictions after computational alanine scanning mutagenesis of ACE2-RBD interface residues. This dataset will help accelerate the design of therapeutics against SARS-CoV-2, as well as contribute to prevention of possible future coronaviruses outbreaks.
Modulation of TRPV-1 by prostaglandin-E2 and bradykinin changes cough sensitivity and autonomic regulation of cardiac rhythm in healthy subjects
Authors: Liviero Filippo , Scarpa Maria Cristina , De Stefani Diego , Folino Franco , Campisi Manuela , Mason Paola , Iliceto Sabino , Pavanello Sofia , Maestrelli Piero 
Published: September 2020

AbstractA neurogenic pathway, involving airway TRPV-1, has been implicated in acute cardiovascular events occurring after peaks of air pollution. We tested whether inhaled prostaglandin-E2 (PGE2) and bradykinin (BK) regulate TRPV-1 activity in vivo by changing cough response to capsaicin (CPS) and affecting heart rate variability (HRV), while also taking into account the influence of TRPV-1 polymorphisms (SNPs). Moreover, we assessed the molecular mechanism of TRPV-1 modulation in vitro. Seventeen healthy volunteers inhaled 100 μg PGE2, 200 μg BK or diluent in a randomized double-blind fashion. Subsequently, the response to CPS was assessed by cough challenge and the sympathetic activity by HRV, expressed by low (nLF) and high (nHF) normalized frequency components, as well as nLF/nHF ratio. Intracellular [Ca2+] was measured in HeLa cells, transfected with wild-type TRPV-1, pre-treated with increasing doses of PGE2, BK or diesel exhaust particulate (DEP), after CPS stimulation. Six functional TRPV-1 SNPs were characterized in DNA from each subject. Inhalation of PGE2 and BK was associated with significant increases in cough response induced by 30 μM of CPS (cough number after PGE2 = 4.20 ± 0.42; p < 0.001, and after BK = 3.64 ± 0.37; p < 0.01), compared to diluent (2.77 ± 0.29) and in sympathetic activity (nLF/nHF ratio after PGE2 = 6.1; p < 0.01, and after BK = 4.2; p < 0.05), compared to diluent (2.5–3.3). No influence of SNPs was observed on autonomic regulation and cough sensitivity. Unlike PGE2 and BK, DEP directly activated TRPV-1. Inhalation of PGE2 and BK sensitizes TRPV-1 and is associated with autonomic dysregulation of cardiac rhythm in healthy subjects.
New insights and best practices for the successful use of Empirical Mode Decomposition, Iterative Filtering and derived algorithms
Authors: Stallone Angela , Cicone Antonio , Materassi Massimo 
Published: September 2020

AbstractAlgorithms based on Empirical Mode Decomposition (EMD) and Iterative Filtering (IF) are largely implemented for representing a signal as superposition of simpler well-behaved components called Intrinsic Mode Functions (IMFs). Although they are more suitable than traditional methods for the analysis of nonlinear and nonstationary signals, they could be easily misused if their known limitations, together with the assumptions they rely on, are not carefully considered. In this work, we examine the main pitfalls and provide caveats for the proper use of the EMD- and IF-based algorithms. Specifically, we address the problems related to boundary errors, to the presence of spikes or jumps in the signal and to the decomposition of highly-stochastic signals. The consequences of an improper usage of these techniques are discussed and clarified also by analysing real data and performing numerical simulations. Finally, we provide the reader with the best practices to maximize the quality and meaningfulness of the decomposition produced by these techniques. In particular, a technique for the extension of signal to reduce the boundary effects is proposed; a careful handling of spikes and jumps in the signal is suggested; the concept of multi-scale statistical analysis is presented to treat highly stochastic signals.
Temporal and spatial Mycobacterium bovis prevalence patterns as evidenced in the All Wales Badgers Found Dead (AWBFD) survey of infection 2014–2016
Authors: Schroeder Paul , Hopkins Beverley , Jones Jeff , Galloway Terry , Pike Ryan , Rolfe Simon , Hewinson Glyn 
Published: September 2020

AbstractIn order to better understand the spatial spread of bovine tuberculosis (bTB) in Wales, an All Wales Badgers Found Dead (AWBFD) survey was carried out from 2014–2016. For Wales, as a whole, there was a significant decrease (p < 0.001) in prevalence of bTB in badgers since a similar survey was carried out in 2005–2006, with a drop from 13.3% to 7.3%. The highest prevalence was observed for the High TB Area East (18.6%), which shares its border with England, and differed significantly (p < 0.001) from the High TB Area West (7.4%). The lowest proportion of carcases diagnosed with the disease (0.7%) was in the Low TB Area, followed by the two Intermediate TB Areas of Wales (2.7%). The M. bovis isolates from badgers tended to be similar to the genotypes of cattle in the same area, except in the Low TB Area. The direction of any cross species transmission and the drivers for this cannot be determined from this study. The spatial variations described here support the need for regionally adapted surveillance and control measures for bovine tuberculosis in Wales.
The role of valve stiffness in the insurgence of deep vein thrombosis
Authors: Schofield Zoe , Baksamawi Hosam Alden , Campos Joana , Alexiadis Alessio , Nash Gerard B. , Brill Alexander , Vigolo Daniele 
Published: September 2020

AbstractDeep vein thrombosis is a life-threatening development of blood clots in deep veins. Immobility and blood flow stagnancy are typical risk factors indicating that fluid dynamics play an important role in the initiation of venous clots. However, the roles of physical parameters of the valves and flow conditions in deep vein thrombosis initiation have not been fully understood. Here, we describe a microfluidics in vitro method that enabled us to explore the role of valve elasticity using in situ fabrication and characterisation. In our experimental model the stiffness of each valve leaflet can be controlled independently, and various flow conditions were tested. The resulting complex flow patterns were detected using ghost particle velocimetry and linked to localised thrombus formation using whole blood and an aqueous suspension of polystyrene particles. In particular, valves with leaflets of similar stiffness had clot formation on the valve tips whereas valves with leaflets of different stiffness had clot formation in the valve pocket.
Atorvastatin improves the proliferation and migration of endothelial progenitor cells via the miR-221/VEGFA axis
Authors: Sun Lihua , Zhang Ying , Zhang Junshi , Wang Juan , Xing Shifeng 
Published: September 2020

Abstract
The present study was aimed at investigating the detailed functions of atorvastatin, a lipid-lowering agent, in the pathogenesis of coronary slow flow (CSF), a clinical disease characterized by delayed angiographic coronary opacity without obstructive coronary disease. In the present study, we successfully identified isolated endothelial progenitor cells (EPCs) from the peripheral blood of patients with CSF. Their vascular endothelial growth factor-A (VEGFA) protein levels were determined using immunoblotting analyses. We determined cell viability using MTT assays, cell migration capacity using Transwell assays, and the angiogenic capacity using a tube formation assay. The target association between miR-221 and VEGFA was validated with a luciferase reporter assay. Atorvastatin treatment increased EPC VEGFA protein levels, proliferation, migration, and angiogenesis. miR-221 expression was down-regulated after atorvastatin treatment; miR-221 overexpression exerted an opposing effect to atorvastatin treatment on VEGFA protein, EPC proliferation, migration, and angiogenesis. The protective effects of atorvastatin treatment on VEGFA protein and EPCs could be significantly suppressed by miR-221 overexpression. miR-221 directly bound the VEGFA 3′UTR to inhibit its expression. In conclusion, atorvastatin improves the cell proliferation, migration, and angiogenesis of EPCs via the miR-221/VEGFA axis. Thus, atorvastatin could be a potent agent against CSF, pending further in vivo and clinical investigations.
Association of UGT1A1*6 polymorphism with irinotecan-based chemotherapy reaction in colorectal cancer patients: a systematic review and a meta-analysis
Authors: Zhu Xiaoyun , Ma Ruchao , Ma Xin , Yang Gang 
Published: September 2020

Abstract
Colorectal cancer (CRC) is a leading cause of cancer-related deaths across the world. Irinotecan (IRI) is commonly used to treat CRC, and IRI-based chemotherapy is linked with adverse reaction and the efficacy of the treatment regimen. The gene UGT1A1 plays a central role in the IRI metabolic pathway. A polymorphism UGT1A1*6 has been widely researched which may be related to response of IRI-based chemotherapy in CRC. All relevant studies were strictly searched from PubMed, Embase, Cochrane Library and Web of Science databases to explore the associations between UGT1A1*6 and response of IRI-based chemotherapy with CRC. Nine articles comprising 1652 patients were included in the final combination. Meta-analysis showed G allele or GG had a lower risk of severe late-onset diarrhea compared with A/AA in allele model and homozygote model (G vs. A: OR = 0.53, 95% CI: 0.28–0.99, P=0.05; GG vs. AA: OR = 0.48, 95% CI: 0.23–0.99, P=0.05), no significant association was observed in other models. In addition, a significant association between UGT1A1*6 and neutropenia was observed in all models (G vs. A: OR = 0.57, 95% CI: 0.46–0.71, P=0.00; GG vs. AA: OR = 0.28, 95% CI: 0.17–0.45, P=0.01; GA vs. AA: OR = 0.42, 95% CI: 0.26–0.70, P=0.00; GG+GA vs. AA: OR = 0.32, 95% CI: 0.20–0.52, P=0.00; GG vs. AA+GA: OR = 0.40, 95% CI: 0.22–0.71, P=0.00), whereas, no relationship was found between UGT1A1*6 and clinical response among the different genotypes. UGT1A1*6 may be considered as a biomarker for IRI-based chemotherapy in CRC.
Prediction of gastric cancer risk: association between ZBTB20 genetic variance and gastric cancer risk in Chinese Han population
Authors: Bai Fei , Xiao Ke 
Published: September 2020

Abstract
Background: Gastric cancer (GC) is a complex multifactorial disease. Previous studies have revealed genetic variations associated with the risk of gastric cancer. The purpose of the present study was to determine the correlation between single-nucleotide polymorphisms (SNPs) of ZBTB20 and the risk of gastric cancer in Chinese Han population.
Methods: We conducted a ‘case–control’ study involving 509 GC patients and 507 healthy individuals. We selected four SNPs of ZBTB20 (10934270 T/C, rs9288999 G/A, rs9841504 G/C and rs73230612 C/T), and used logistic regression to analyze the relationship between those SNPs and GC risk under different genetic models; multi-factor dimensionality reduction (MDR) was used to analyze the interaction of “SNP–SNP” in gastric cancer risk; ANOVA and univariate analysis were used to analyze the differences in clinical characteristics among different genotypes.
Results: Our results showed that ZBTB20 rs9288999 is a protective factor for the risk of gastric cancer in multiple genetic models, of which the homozygous model is the most significant (OR = 0.48, P=0.0003); we also found that rs9288999 showed a significant correlation with reducing the risk of gastric cancer in different subgroups (BMI; age; gender; smoking or drinking status; adenocarcinoma); rs9841504 is associated with increased GC risk in the participants with BMI&gt;24 kg/m2; rs9841504 and rs73230612 are certainly associated with clinical characteristics of platelet and carbohydrate antigen 242, respectively.
Conclusion: Our results suggest that ZBTB20 rs9288999 may be important for reducing the risk of GC in the Chinese Han population.
The molecular mechanism of mechanotransduction in vascular homeostasis and disease
Authors: Yamashiro Yoshito , Yanagisawa Hiromi 
Published: September 2020

Abstract
Blood vessels are constantly exposed to mechanical stimuli such as shear stress due to flow and pulsatile stretch. The extracellular matrix maintains the structural integrity of the vessel wall and coordinates with a dynamic mechanical environment to provide cues to initiate intracellular signaling pathway(s), thereby changing cellular behaviors and functions. However, the precise role of matrix–cell interactions involved in mechanotransduction during vascular homeostasis and disease development remains to be fully determined. In this review, we introduce hemodynamics forces in blood vessels and the initial sensors of mechanical stimuli, including cell–cell junctional molecules, G-protein-coupled receptors (GPCRs), multiple ion channels, and a variety of small GTPases. We then highlight the molecular mechanotransduction events in the vessel wall triggered by laminar shear stress (LSS) and disturbed shear stress (DSS) on vascular endothelial cells (ECs), and cyclic stretch in ECs and vascular smooth muscle cells (SMCs)—both of which activate several key transcription factors. Finally, we provide a recent overview of matrix–cell interactions and mechanotransduction centered on fibronectin in ECs and thrombospondin-1 in SMCs. The results of this review suggest that abnormal mechanical cues or altered responses to mechanical stimuli in EC and SMCs serve as the molecular basis of vascular diseases such as atherosclerosis, hypertension and aortic aneurysms. Collecting evidence and advancing knowledge on the mechanotransduction in the vessel wall can lead to a new direction of therapeutic interventions for vascular diseases.
Vitamin D deficiency promotes large rupture-prone abdominal aortic aneurysms and cholecalciferol supplementation limits progression of aneurysms in a mouse model
Authors: Nsengiyumva Vianne , Krishna Smriti M. , Moran Corey S. , Moxon Joseph V. , Morton Susan K. , Clarke Michael W. , Seto Sai-Wang , Golledge Jonathan 
Published: September 2020

Abstract
Vitamin D deficiency has been associated with human abdominal aortic aneurysm (AAA); however, its role in AAA pathogenesis is unclear. The aim of the present study was to investigate the effect of vitamin D deficiency on AAA development and examine if administering cholecalciferol (CCF) could limit growth of established AAA within the angiotensin-II (AngII) infused apolipoprotein E-deficient mouse model. Mice were rendered vitamin D deficiency through dietary restriction and during AngII infusion developed larger AAAs as assessed by ultrasound and ex vivo morphometry that ruptured more commonly (48% vs. 19%; P=0.028) than controls. Vitamin D deficiency was associated with increased aortic expression of osteopontin and matrix metalloproteinase-2 and -9 than controls. CCF administration to mice with established aortic aneurysms limited AAA growth as assessed by ultrasound (P&lt;0.001) and ex vivo morphometry (P=0.036) and reduced rupture rate (8% vs. 46%; P=0.031). This effect was associated with up-regulation of circulating and aortic sclerostin. Incubation of human aortic smooth muscle cells with 1,25-dihyroxyvitamin D3 (the active metabolite of vitamin D) for 48 h induced up-regulation of sclerostin (P&lt;0.001) and changed the expression of a range of other genes important in extracellular matrix remodeling. The present study suggests that vitamin D deficiency promotes development of large rupture-prone aortic aneurysms in an experimental model. CCF administration limited both growth and rupture of established aneurysms. These effects of vitamin D appeared to be mediated via changes in genes involved in extracellular matrix remodeling, particularly sclerostin.
Electrophysiological Evidence of Early Cortical Sensitivity to Human Conspecific Mimic Voice as a Distinct Category of Natural Sound
Authors: Talkington William J. , Donai Jeremy , Kadner Alexandra S. , Layne Molly L. , Forino Andrew , Wen Sijin , Gao Si , Gray Margeaux M. , Ashraf Alexandria J. , Valencia Gabriela N. , Smith Brandon D. , Khoo Stephanie K. , Gray Stephen J. , Lass Norman , Brefczynski-Lewis Julie A. , Engdahl Susannah , Graham David , Frum Chris A. , Lewis James W. 
Published: September 2020

PurposeFrom an anthropological perspective of hominin communication, the human auditory system likely evolved to enable special sensitivity to sounds produced by the vocal tracts of human conspecifics whether attended or passively heard. While numerous electrophysiological studies have used stereotypical human-produced verbal (speech voice and singing voice) and nonverbal vocalizations to identify human voice–sensitive responses, controversy remains as to when (and where) processing of acoustic signal attributes characteristic of “human voiceness” per se initiate in the brain.MethodTo explore this, we used animal vocalizations and human-mimicked versions of those calls (“mimic voice”) to examine late auditory evoked potential responses in humans.ResultsHere, we revealed an N1b component (96–120 ms poststimulus) during a nonattending listening condition showing significantly greater magnitude in response to mimics, beginning as early as primary auditory cortices, preceding the time window reported in previous studies that revealed species-specific vocalization processing initiating in the range of 147–219 ms. During a sound discrimination task, a P600 (500–700 ms poststimulus) component showed specificity for accurate discrimination of human mimic voice. Distinct acoustic signal attributes and features of the stimuli were used in a classifier model, which could distinguish most human from animal voice comparably to behavioral data—though none of these single features could adequately distinguish human voiceness.ConclusionsThese results provide novel ideas for algorithms used in neuromimetic hearing aids, as well as direct electrophysiological support for a neurocognitive model of natural sound processing that informs both neurodevelopmental and anthropological models regarding the establishment of auditory communication systems in humans.Supplemental Materialhttps://doi.org/10.23641/asha.12903839