bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using machine learning to understand neuromorphological change and image‐based biomarker identification in Cavalier King Charles Spaniels with Chiari‐like malformation‐associated pain and syringomyelia
Authors: Spiteri Michaela , Knowler Susan P. , Rusbridge Clare , Wells Kevin 
Published: September 2019

AbstractBackgroundChiari‐like malformation (CM) is a complex malformation of the skull and cranial cervical vertebrae that potentially results in pain and secondary syringomyelia (SM). Chiari‐like malformation‐associated pain (CM‐P) can be challenging to diagnose. We propose a machine learning approach to characterize morphological changes in dogs that may or may not be apparent to human observers. This data‐driven approach can remove potential bias (or blindness) that may be produced by a hypothesis‐driven expert observer approach.Hypothesis/ObjectivesTo understand neuromorphological change and to identify image‐based biomarkers in dogs with CM‐P and symptomatic SM (SM‐S) using a novel machine learning approach, with the aim of increasing the understanding of these disorders.AnimalsThirty‐two client‐owned Cavalier King Charles Spaniels (CKCSs; 11 controls, 10 CM‐P, 11 SM‐S).MethodsRetrospective study using T2‐weighted midsagittal Digital Imaging and Communications in Medicine (DICOM) anonymized images, which then were mapped to images of an average clinically normal CKCS reference using Demons image registration. Key deformation features were automatically selected from the resulting deformation maps. A kernelized support vector machine was used for classifying characteristic localized changes in morphology.ResultsCandidate biomarkers were identified with receiver operating characteristic curves with area under the curve (AUC) of 0.78 (sensitivity 82%; specificity 69%) for the CM‐P biomarkers collectively and an AUC of 0.82 (sensitivity, 93%; specificity, 67%) for the SM‐S biomarkers, collectively.Conclusions and clinical importanceMachine learning techniques can assist CM/SM diagnosis and facilitate understanding of abnormal morphology location with the potential to be applied to a variety of breeds and conformational diseases.
Genetic alterations of KIT during clonal expansion and subsequent acquisition of resistance to toceranib in a canine mast cell tumor cell line
Authors: Kurita Sena , Miyamoto Ryo , Tani Hiroyuki , Kobayashi Masato , Sasaki Takashi , Tamura Kyoichi , Bonkobara Makoto 
Published: September 2019

AbstractOne of the potential mechanisms underlying acquired resistance to toceranib in canine mast cell tumor (MCT) is the emergence of a secondary mutation in the KIT gene. Here, genetic alterations of KIT during clonal expansion and subsequent acquisition of resistance to toceranib were investigated in the toceranib‐susceptible canine MCT cell line VI‐MC, which carries a KIT‐activating mutation resulting in a predicted p.(Asn508Ile) amino acid change in the receptor tyrosine kinase protein KIT. Two sublines were cloned from VI‐MC and toceranib‐resistant sublines then were established by continuous exposure to toceranib. The mutation status of KIT in parental VI‐MC and its sublines was investigated using next‐generation sequencing (NGS). Additionally, effects of secondary mutations on toceranib sensitivity in p.(Asn508Ile)‐mutant KIT were examined. KIT secondary mutations, including those encoding p.(Asn679Lys)‐, p.(Asp819Val)‐, and p.(Asp819Gly)‐mutant KIT, that confer toceranib insensitivity to p.(Asn508Ile)‐mutant KIT emerged only in toceranib‐resistant VI‐MCs. These mutations were not detected by NGS in the parental VI‐MC line or in the toceranib‐naive cloned VI‐MCs, although the parental line and sublines exhibited genetic heterogeneity in KIT that may have been caused by genetic evolution during clonal expansion. VI‐MC clones with these secondary mutations in KIT appear to have arisen from subclones during treatment with toceranib rather than being pre‐existing. However, further study using a higher resolution technique will be needed to confirm the developmental mechanism of KIT secondary mutation in canine MCT cells with acquired resistance to toceranib.
Structure and function of lipid A–modifying enzymes
Authors: Anandan Anandhi , Vrielink Alice 
Published: September 2019

AbstractLipopolysaccharides are complex molecules found in the cell envelop of many Gram‐negative bacteria. The toxic activity of these molecules has led to the terminology of endotoxins. They provide bacteria with structural integrity and protection from external environmental conditions, and they interact with host signaling receptors to induce host immune responses. Bacteria have evolved enzymes that act to modify lipopolysaccharides, particularly the lipid A region of the molecule, to enable the circumvention of host immune system responses. These modifications include changes to lipopolysaccharide by the addition of positively charged sugars, such as N‐Ara4N, and phosphoethanolamine (pEtN). Other modifications include hydroxylation, acylation, and deacylation of fatty acyl chains. We review the two‐component regulatory mechanisms for enzymes that carry out these modifications and provide details of the structures of four enzymes (PagP, PagL, pEtN transferases, and ArnT) that modify the lipid A portion of lipopolysaccharides. We focus largely on the three‐dimensional structures of these enzymes, which provide an understanding of how their substrate binding and catalytic activities are mediated. A structure–function–based understanding of these enzymes provides a platform for the development of novel therapeutics to treat antibiotic resistance.
On higher direct images of convergent isocrystals
Authors: Xu Daxin 
Published: September 2019

Let $k$ be a perfect field of characteristic $p>0$ and let $\operatorname{W}$ be the ring of Witt vectors of $k$. In this article, we give a new proof of the Frobenius descent for convergent isocrystals on a variety over $k$ relative to $\operatorname{W}$. This proof allows us to deduce an analogue of the de Rham complexes comparison theorem of Berthelot [$\mathscr{D}$-modules arithmétiques. II. Descente par Frobenius, Mém. Soc. Math. Fr. (N.S.) 81 (2000)] without assuming a lifting of the Frobenius morphism. As an application, we prove a version of Berthelot’s conjecture on the preservation of convergent isocrystals under the higher direct image by a smooth proper morphism of $k$-varieties.
Identification of key microRNAs and genes associated with abdominal aortic aneurysm based on the gene expression profile
Authors: Yang Pu , Cai Zhou , Wu Kai , Hu Yu , Liu Ling , Liao Mingmei 
Published: September 2019

New Findings
What is the central question of this study?
The aim was to identify abdominal aortic aneurysm (AAA)‐associated microRNAs and their target genes in AAA using microarray analysis.

What is the main finding and its importance?
The main finding was that miR‐145 and miR‐30c‐2* were found to be downregulated microRNAs in AAA, which could exert suppressive effects on AAA progression, and that miR‐145 might target RAC2, whereas miR‐30c‐2* might target PIK3CD, IL1B and RAC2. The findings obtained from the study provide an enhanced understanding of microRNA as a therapeutic target to limit AAA.

AbstractThe aim of the study was to identify abdominal aortic aneurysm (AAA)‐associated microRNAs (miRNAs) and genes potentially contributing to AAA. Differential analysis was performed to screen out differentially expressed genes (DEGs) and miRNAs in expression datasets of AAA‐related miRNAs [GSE51226 (mouse)] and genes [GSE51227 (mouse) and GSE7084 (human)]. Then, gene ontology (GO) enrichment analysis of DEGs was compared with aneurysm‐related GO to screen out DEGs related to the disease. The target genes of differential miRNAs were predicted and used to construct a miRNA–DEG regulatory network, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of target genes. Moreover, the protein–protein interaction network of target genes of miRNAs in the core position (hub‐miRNA) with AAA‐related genes was constructed to screen out hub genes. Finally, the target relationship between hub‐miRNAs and their target genes was verified. There were 20 upregulated miRNAs and 20 downregulated miRNAs in AAA screened from the GSE51226 dataset (mouse). In addition, there were 1154 upregulated genes and 821 downregulated genes in the GSE51227 dataset (mouse), of which 246 DEGs were enriched in aneurysm‐related GO entries in AAA. miR‐145 and miR‐30c‐2* were the key miRNAs of AAA, both of which were downregulated in AAA and influenced pathways so as to affect AAA by regulating their respective target genes. The disease‐related gene ACTA2 was downregulated, whereas DEGs including PIK3CD, IL1B, RAC2 and SELL were upregulated in AAA. Finally, it was proved that miR‐145 targeted RAC2 and SELL, whereas miR‐30c‐2* targeted PIK3CD, IL1B and RAC2. Taken together, miR‐145 and miR‐30c‐2*, downregulated in AAA, could potentially affect AAA, and miR‐145 might target RAC2, whereas miR‐30c‐2* might target PIK3CD, IL1B and RAC2.
Highly Active Electrode With Efficiently Added Surface Oxygen Groups for a Vanadium Redox Flow Battery
Authors: Ishitobi Hirokazu , Sugawara Satoshi , Oba Kosuke , Hirano Takumi , Doki Honoka , Handa Yusuke , Sato Yuma , Yamamoto Shunya , Nakagawa Nobuyoshi 
Published: September 2019

AbstractHigher power output by a lower kinetic resistance of the vanadium redox flow battery is needed for its commercialization. In this study, we focused on the air oxidation conditions of carbon paper, which is the electrode material, to reduce the kinetic resistance. The air oxidation is considered to affect the number of surface oxygen groups such as the phenol-type hydroxyl group due to oxidation of the carbon fiber. The surface oxygen groups may correspond to the active sites for the charge/discharge reaction. We quantitatively evaluated the number of surface oxygen groups by temperature-programmed desorption. In addition, we measured the double-layer capacitances of the carbon papers, which may reflect the surface area of the carbon fiber. The single-cell performances, i.e., current–voltage curves and charge–discharge profile, of the electrodes were studied. The air oxidized carbon paper, heat-treated at 500 °C for 3 h (8.4% mass decrease from the pristine sample), showed the highest power density (960 mW cm−2) in this study with thin electrode material (ca., 0.2 mm for one sheet). The negative half-reaction was enhanced by air oxidation. This result could be explained by the reduction of the kinetic resistance by increasing the number of phenol groups, and this power output was relatively high as the vanadium redox flow battery by using a commercial carbon paper and the standard flow field.
Providing a Basis for Harmonization of Accelerometer-Assessed Physical Activity Outcomes Across Epidemiological Datasets
Authors: Rowlands Alex V. , Plekhanova Tatiana , Yates Tom , Mirkes Evgeny M. , Davies Melanie , Khunti Kamlesh , Edwardson Charlotte L. 
Published: September 2019

Introduction: To capitalize on the increasing availability of accelerometry data for epidemiological research it is desirable to compare and/or pool data from surveys worldwide. This study aimed to establish whether free-living physical activity outcomes can be considered equivalent between three research-grade accelerometer brands worn on the dominant and non-dominant wrist. Of prime interest were the average acceleration (ACC) and the intensity gradient (IG). These two metrics describe the volume and intensity of the complete activity profile; further, they are comparable across populations making them ideal for comparing and/or pooling activity data. Methods: Forty-eight adults wore a GENEActiv, Axivity, and ActiGraph on both wrists for up to 7-days. Data were processed using open-source software (GGIR) to generate physical activity outcomes, including ACC and IG. Agreement was assessed using pairwise 95% equivalence tests (±10% equivalence zone) and intra-class correlation coefficients (ICC). Results: ACC was equivalent between brands when measured at the non-dominant wrist (ICC ≥ 0.93), but approximately 10% higher when measured at the dominant wrist (GENEActiv and Axivity only, ICC ≥ 0.83). The IG was equivalent irrespective of monitor brand or wrist (ICC ≥ 0.88). After adjusting ACC measured at the dominant wrist by −10% (GENEActiv and Axivity only), ACC was also within (or marginally outside) the 10% equivalence zone for all monitor pairings. Conclusion: If average acceleration is decreased by 10% for studies deploying monitors on the dominant wrist (GENEActiv and Axivity only), ACC and IG may be suitable for comparing and/or collating physical activity outcomes across accelerometer datasets, regardless of monitor brand and wrist.
The Association Between Neighborhood Socioeconomic Deprivation, Cardiorespiratory Fitness, and Physical Activity in US Youth
Authors: Clennin Morgan N. , Pate Russell R. 
Published: September 2019

Background: Growing evidence suggests that the broader neighborhood socioeconomic environment is independently associated with cardiometabolic health. However, few studies have examined this relationship among younger populations. Purpose: The purpose of the study was to (1) investigate the association between neighborhood socioeconomic deprivation (SED) and cardiorespiratory fitness and (2) determine the extent to which physical activity mediates this relationship. Methods: Data from 312 youth (aged 12–15 y) were obtained from the 2012 National Health and Nutrition Examination Survey National Youth Fitness Survey. Cardiorespiratory fitness was measured using a standard submaximal treadmill test, and maximal oxygen consumption was estimated. Physical activity was self-reported time spent in moderate to vigorous activity. Neighborhood SED was measured by a composite index score at the census tract of residence. Logistic regression analyses examined relationships between neighborhood SED, physical activity, and cardiorespiratory fitness, adjusting for individual-level characteristics and the complex sampling design. Results: Neighborhood SED was not significantly associated with cardiorespiratory fitness or physical activity among youth in the study sample. Conclusions: While not significant, cardiorespiratory fitness levels were observed to decrease as neighborhood SED increased. Future research is needed to better understand this relationship and to identify underlying mechanisms beyond fitness or physical activity that may drive the relationship between neighborhood SED and health.
The effects of a pre-exercise meal on postexercise metabolism following a session of sprint interval training
Authors: Broad Abigail A. , Howe Greg J. , McKie Greg L. , Vanderheyden Luke W. , Hazell Tom J. 
Published: September 2019

Sprint interval training (SIT) has demonstrated reductions in fat mass through potential alterations in postexercise metabolism. This study examined whether exercising in the fasted or fed state affects postexercise metabolism following acute SIT. Ten active males performed a bout of modified SIT (8 × 15-s sprints; 120 s recovery) in both a fasted (FAST) and fed (FED) state. Gas exchange was collected through 3 h postexercise, appetite perceptions were measured using a visual analog scale, and energy intake was recorded using dietary food logs. There was no difference in energy expenditure between conditions at any time point (p > 0.329) or in total session energy expenditure (FED: 514.8 ± 54.9 kcal, FAST: 504.0 ± 74.3 kcal; p = 0.982). Fat oxidation at 3 h after exercise was higher in FED (0.110 ± 0.04 g·min−1) versus FAST (0.069 ± 0.02 g·min−1; p = 0.013) though not different between conditions across time (p > 0.340) or in total postexercise fat oxidation (FED: 0.125 ± 0.04 g·min−1, FAST: 0.105 ± 0.02 g·min−1; p = 0.154). Appetite perceptions were lower in FED (–4815.0 ± 4098.7 mm) versus FAST (–707.5 ± 2010.4 mm, p = 0.022); however, energy intake did not differ between conditions (p = 0.429). These results demonstrate the fasted or fed state does not augment postexercise metabolism following acute SIT in a way that would favour fat loss following training. Novelty Energy expenditure was similar between conditions, while fat oxidation was significantly greater in FED at 3 h after exercise. Appetite perceptions were significantly lower in FED; however, energy intake was not different between conditions. Current findings suggest that performing SIT in the fed or fasted state would not affect fat loss following training.
Non-perturbative determination of improvement coefficients $$b_\mathrm{m}$$ and $$b_\mathrm{A}-b_\mathrm{P}$$ and normalisation factor $$Z_\mathrm{m}Z_\mathrm{P}/Z_\mathrm{A}$$ with $$N_\mathrm{f}= 3$$ Wilson fermions
Authors: de Divitiis Giulia Maria , Fritzsch Patrick , Heitger Jochen , Köster Carl Christian , Kuberski Simon , Vladikas Anastassios 
Published: September 2019

Abstract
We determine non-perturbatively the normalisation parameter $$Z_\mathrm{m}Z_\mathrm{P}/Z_\mathrm{A}$$ZmZP/ZA as well as the Symanzik coefficients $$b_\mathrm{m}$$bm and $$b_\mathrm{A}-b_\mathrm{P}$$bA-bP, required in $$\mathrm{O}(a)$$O(a) improved quark mass renormalisation with Wilson fermions. The strategy underlying their computation involves simulations in $$N_\mathrm{f}=3$$Nf=3 QCD with $$\mathrm{O}(a)$$O(a) improved massless sea and non-degenerate valence quarks in the finite-volume Schrödinger functional scheme. Our results, which cover the typical gauge coupling range of large-volume $$N_\mathrm{f}=2+1$$Nf=2+1 QCD simulations with Wilson fermions at lattice spacings below $$0.1\,\mathrm{fm}$$0.1fm, are of particular use for the non-perturbative calculation of $$\mathrm{O}(a)$$O(a) improved renormalised quark masses.
Post Genome-Wide Gene–Environment Interaction Study Using Random Survival Forest: Insulin Resistance, Lifestyle Factors, and Colorectal Cancer Risk
Authors: Jung Su Yon , Papp Jeanette C. , Sobel Eric M. , Zhang Zuo-Feng 
Published: September 2019

Abstract
Molecular and genetic pathways of insulin resistance (IR) connecting colorectal cancer and obesity factors in postmenopausal women remain inconclusive. We examined the IR pathways on both genetic and phenotypic perspectives at the genome-wide level. We further constructed colorectal cancer risk profiles with the most predictive IR SNPs and lifestyle factors. In our earlier genome-wide association gene–environmental interaction study, we used data from a large cohort of postmenopausal women in the Women's Health Initiative Database for Genotypes and Phenotypes Study and identified 58 SNPs in relation to IR phenotypes. In this study, we evaluated the identified IR SNPs and selected 34 lifestyles for their association with colorectal cancer risk in a total of 11,078 women (including 736 women with colorectal cancer) using a 2-stage multimodal random survival forest analysis. In overall and subgroup (defined via body mass index, exercise, and dietary-fat intake) analyses, we identified 2 SNPs (LINC00460 rs1725459 and MTRR rs722025) and lifetime cumulative exposure to estrogen (oral contraceptive use) and cigarette smoking as the most common and strongest predictive markers for colorectal cancer risk across the analyses. The combinations of genetic and lifestyle factors had much greater impact on colorectal cancer risk than any individual risk factors, and a possible synergism existed to increase colorectal cancer risk in a gene-behavior dose-dependent manner. Our findings may inform research on the role of IR in the etiology of colorectal cancer and contribute to more accurate prediction of colorectal cancer risk, suggesting potential intervention strategies for women with specific genotypes and lifestyles to reduce their colorectal cancer risk.
Neoplatonic Providence and Descent: a Test-Case from Proclus’ Alcibiades Commentary
Authors: Vasilakis D.A. 
Published: September 2019

Abstract
This article deals with the complex relation between providence and descent in Neoplatonism, with particular reference to Proclus and especially his Commentary on the First Alcibiades. At least according to this work, descent is only a species of providence, because there can be providence without any descent. Whereas the gods (for instance the Henads) provide for our cosmos without descending to it, a large group of souls provide for our cosmos by descending to it. The former kind of providence is better than the latter, even if it is necessary that souls descend in order to give existence to the beautiful cosmos. The following study deals with providence as descent, looking at it from two angles. In the first section I show that Proclus designates this form of providence in two rather surprising ways. One term he uses for it, which will be well known to readers of Plotinus, is τόλµα (audacity)—this despite the word’s negative connotations due to its Neopythagorean and Gnostic origin. A second name for descended providence is ἐπιστροφή (‘reversion’ or better ‘turning one’s attention’). Again, this may be surprising, since we usually expect this term to express the ‘turning back’ of a lower effect to its cause. In Proclus, the word ἐπιστροφή too can have negative connotations, but he also uses it in a positive way when applying it to providence. In the second part of the paper, I explain how Socrates’ providence for Alcibiades (as seen in the Alcibiades I) can be undefiled (i.e. unmixed), even if Socrates necessarily descends as he offers providential guidance. Proclus’ comparison of Socrates with Hercules, who went to the Underworld in order to save Theseus, serves as a positive illustration of Socrates’ divinelike providence, and marks the deficiency of Socrates (or Hercules as a ‘semi-god’) compared to the transcendent and undefiled providence of Neoplatonic divinities.
Restoring T-helper 17 cell/regulatory T-cell balance and decreasing disease activity by rapamycin and all-trans retinoic acid in patients with systemic lupus erythematosus
Authors: Chu Y , Zhao C , Zhang B , Wang X , Wang Y , An J , Chen J 
Published: September 2019

Objective This study aimed to investigate the effect of rapamycin (RAPA) alone or in combination with all-trans retinoic acid (ATRA) on the T-helper 17 (Th17) cell/regulatory T-cell (Treg) balance in patients with systemic lupus erythematosus (SLE) and to evaluate the clinical efficacy. Methods Seventy patients with SLE were enrolled. They were randomly and equally divided into RAPA and RAPA + ATRA groups. The number of Th17 and Treg cells was measured by flow cytometry before and after treatment for 6, 12 and 24 weeks. The SLE Disease Activity Index (SLEDAI) score and the prednisone dose before and after treatment were used to evaluate the efficacy between the two groups. Results In both groups, at different time points after treatment, the number of Th17 cells ( p = 0.003) and Th17/Treg ratio ( p = 0.044) reduced, while the number of Treg cells ( p = 0.574) tended to increase. The SLEDAI score and the dose of prednisone decreased significantly ( p < 0.001). There was no significant difference in the number of Th17 cells ( p = 0.089), Treg cells ( p = 0.059), Th17/Treg ratio ( p = 0.580), SLEDAI score ( p = 0.127) and the dose of prednisone ( p = 0.329) between the two groups. Conclusion Disease activity in SLE patients reduced with RAPA alone or in conjunction with ATRA, reducing glucocorticoid requirement. One of its mechanisms of action may be regulating the Th17/Treg cell balance, which provides a new model for the pathogenesis and potential treatment of SLE.