bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insertion of a transposon‐like sequence in the 5′‐flanking region of the YUCCA gene causes the stony hard phenotype
Authors: Tatsuki Miho , Soeno Kazuo , Shimada Yukihisa , Sawamura Yutaka , Suesada Yuko , Yaegaki Hideaki , Sato Akiko , Kakei Yusuke , Nakamura Ayako , Bai Songling , Moriguchi Takaya , Nakajima Naoko 
Published: August 2018

SummaryMelting‐flesh peaches produce large amounts of ethylene, resulting in rapid fruit softening at the late‐ripening stage. In contrast, stony hard peaches do not soften and produce little ethylene. The indole‐3‐acetic acid (IAA) level in stony hard peaches is low at the late‐ripening stage, resulting in low ethylene production and inhibition of fruit softening. To elucidate the mechanism of low IAA concentration in stony hard peaches, endogenous levels of IAA and IAA intermediates or metabolites were analysed by ultra‐performance liquid chromatography‐tandem mass spectrometry. Although the IAA level was low, the indole‐3‐pyruvic acid (IPyA) level was high in stony hard peaches at the ripening stage. These results indicate that YUCCA activity is reduced in ripening stony hard peaches. The expression of one of the YUCCA isogenes in peach, PpYUC11, was suppressed in ripening stony hard peaches. Furthermore, an insertion of a transposon‐like sequence was found upstream of the PpYUC11 gene in the 5′‐flanking region. Analyses of the segregation ratio of the stony hard phenotype and genotype in F1 progenies indicated that the transposon‐inserted allele of PpYUC11, hd‐t, correlated with the stony hard phenotype. On the basis of the above findings, we propose that the IPyA pathway (YUCCA pathway) is the main auxin biosynthetic pathway in ripening peaches of ‘Akatsuki’ and ‘Manami’ cultivars. Because IAA is not supplied from storage forms, IAAde novo synthesis via the IPyA pathway (YUCCA pathway) in mesocarp tissues is responsible for auxin generation to support fruit softening, and its disruption can lead to the stony hard phenotype.
Fundus examination of 199 851 newborns by digital imaging in China: a multicentre cross-sectional study
Authors: Tang He , Li Na , Li Zhan , Zhang Meiju , Wei Meirong , Huang Changbing , Wang Jihong , Li Fuxin , Wang Hong , Liu Zijiang , He Liying , Cheng Yangyang , Chen Wei , Jin Liwen , Gong Limin , Lu Jun , Xue Yan , Su Manxiang , Wang Yanhong , Mo Haiming , Chen Zhenwen , Guo Wei , Li Yun , Pan Hong , Zhang Wei , Ma Xu , Jin Xi , Wang Binbin ,   On behalf of The collaborating group of neonatal ocular birth defects and genetic diseases in China
Published: August 2018

BackgroundThe prevalence of ocular abnormalities of newborn in China has seldom been reported. To report the implementation of digital imaging in ocular screening of all newborns in multiple centres in China and to describe the abnormal findings of fundus examination, we did the cross-sectional study.MethodsFundus examinations were performed on newborns within the 42 days after birth using a RetCam wide-field digital imaging system. Digital images of the posterior pole, superior, nasal and temporal retinal fields of each participant were taken. All newborns were from eights centres across China from January 2009 to July 2017.ResultsA total of 199 851 newborns were included in the study. We detected 18 198 (9.11%) abnormal cases. The most frequent abnormality was severe retinal haemorrhage (RH) found in 12 810 cases (6.41%). The other anomalies included familial exudative vitreoretinopathy, retinopathy of prematurity, abnormal fundus pigmentation, subconjunctival haemorrhage, choroidal coloboma, idiopathic retinal venous tortuosity, exudative changes and other anomalies with uncertain identities.ConclusionThis large-scale study of newborn fundus examination showed a relatively high prevalence of ocular abnormalities. Hundreds of neonates with rare disorders that severely impair ocular health were also detected at an early age. The long-term impact of other anomalies including RHs on the ocular system should be investigated by a perspective study. Our study suggested that fundus examination of newborns can play a beneficial role in ocular health.
Repeatability and comparability of peripapillary vessel density measurements of high-density and non-high-density optical coherence tomography angiography scans in normal and glaucoma eyes
Authors: Venugopal Jayasree P , Rao Harsha Laxmana , Weinreb Robert N , Dasari Srilakshmi , Riyazuddin Mohammed , Pradhan Zia Sultan , Puttaiah Narendra K , Devi Sathi , Mansouri Kaweh , Webers Carroll A B 
Published: August 2018

AimsTo compare the peripapillary vessel density (VD) measurements of high-density (HD) and non-HD optical coherence tomography angiography (OCTA) scans in normal and glaucoma eyes, and to evaluate the intrasession repeatability of VD measurements of HD scans.MethodsIn a cross-sectional study, 46 normal (33 subjects) and 89 glaucoma (64 patients) eyes underwent 3 HD and 1 non-HD optic nerve head OCTA scans in the same session. Agreement in VD measurements between HD and non-HD scans was assessed using Bland and Altman analysis. Repeatability of the VD measurements of HD scans was assessed using within-subject coefficient of repeatability (CRw) and variation (CVw).ResultsThe mean difference in the VDs ranged between 0.7% (temporal sector VD) and 2.0% (inferonasal sector VD), with HD scans showing significantly greater VD values than non-HD scans. The 95% limits of agreement (LoA) in glaucoma eyes ranged between −2.0% and 5.0% for whole enface VD and between −4.8% and 9.6% for superotemporal VD. CRw (%) and CVw (%) of VD measurements of HD scans ranged from 3.0 to 4.9 and from 2.0 to 3.1 in normal eyes. The same ranged from 3.2 to 6.7 and from 2.6 to 4.8, respectively, in glaucoma eyes.ConclusionsVD of HD scans was higher than that of non-HD scans. The wide 95% LoA indicates that the VD measurements of HD and non-HD scans cannot be used interchangeably. Test–retest repeatability of VDs on HD scans was as high as 6%. These results should be considered while using OCTA for longitudinal evaluation of glaucoma.
Homozygous variants in KIAA1549, encoding a ciliary protein, are associated with autosomal recessive retinitis pigmentosa
Authors: de Bruijn Suzanne E , Verbakel Sanne K , de Vrieze Erik , Kremer Hannie , Cremers Frans P M , Hoyng Carel B , van den Born L Ingeborgh , Roosing Susanne 
Published: August 2018

BackgroundRetinitis pigmentosa (RP) shows substantial genetic heterogeneity. It has been estimated that in approximately 60%–80% of RP cases, the genetic diagnosis can be found using whole exome sequencing (WES). In this study, the purpose was to identify causative variants in individuals with genetically unexplained retinal disease, which included one consanguineous family with two affected siblings and one case with RP.MethodsTo identify the genetic defect, WES was performed in both probands, and clinical analysis was performed. To obtain insight into the function of KIAA1549 in photoreceptors, mRNA expression, knockdown and protein localisation studies were performed.ResultsThrough analysis of WES data, based on population allele frequencies, and in silico prediction tools, we identified a homozygous missense variant and a homozygous frameshift variant in KIAA1549 that segregate in two unrelated families. Kiaa1549 was found to localise at the connecting cilium of the photoreceptor cells and the synapses of the mouse retina. Both variants affect the long transcript of KIAA1549, which encodes a 1950 amino acid protein and shows prominent brain expression. The shorter transcript encodes a 734 amino acid protein with a high retinal expression and is affected by the identified missense variant. Strikingly, knockdown of the long transcript also leads to decreased expression of the short transcript likely explaining the non-syndromic retinal phenotype caused by the two variants targeting different transcripts.ConclusionIn conclusion, our results underscore the causality of segregating variants in KIAA1549 for autosomal recessive RP. Moreover, our data indicate that KIAA1549 plays a role in photoreceptor function.
Difference between recommended retail price and sales price for tobacco products in independent and convenience (small) retailers before and after the introduction of standardised tobacco packaging in the UK
Authors: Critchlow Nathan , Stead Martine , Moodie Crawford , Angus Kathryn , Eadie Douglas , MacKintosh Anne-Marie 
Published: August 2018

AimRecommended retail price (RRP) is a marketing strategy used by tobacco companies to maintain competitiveness, communicate product positioning and drive sales. We explored small retailer adherence to RRP before and after the introduction of the Standardised Packaging of Tobacco Products Regulations in the UK (fully implemented on 20 May 2017) which mandated standardised packaging of cigarettes and rolling tobacco, set minimum pack/pouch sizes and prohibited price-marking.MethodMonthly electronic point of sale data from 500 small retailers in England, Scotland and Wales were analysed. From May 2016 to October 2017, we monitored 20 of the best-selling fully branded tobacco products (15 factory-made cigarettes, 5 rolling tobacco) and their standardised equivalents. Adherence to RRP was measured as the average difference (%) between monthly RRPs and sales prices by pack type (fully branded vs standardised), price-marking on packaging and price segment.ResultsThe average difference between RRP and sales price increased from +0.36% above RRP (SD=0.72) in May 2016, when only fully branded packs were sold, to +1.37% in October 2017 (SD=0.30), when standardised packs were mandatory. Increases above RRP for fully branded packs increased as they were phased out, with deviation greater for non-price-marked packs and premium products.DiscussionDespite tobacco companies emphasising the importance of RRP, small retailers implemented small increases above RRP as standardised packaging was introduced. Consequently, any intended price changes by tobacco companies in response to the legislation (ie, to increase affordability or brand positioning) may be confounded by retailer behaviour, and such deviation may increase consumer price sensitivity.
Comprehensive compensation method for thermal error of vertical drilling center
Authors: Kang Cheng Ming , Zhao Chun Yu , Liu Kuo , Li Tie Jun , Yang Bo 
Published: August 2018

To eliminate the influence of thermally induced error from a machine tool on machining accuracy, a comprehensive error compensation method for thermal displacement of the screw shaft and spindle is put forward. Based on a heat transfer mechanism and experimental analysis, a model of screw thermal expansion error is built. Modeling of spindle thermal growth that depends on speed variations is also proposed. Thermal tests for studying thermal behavior of the spindle and screw axis are carried out on the vertical drilling center TC500R. Finally, the compensation effect of the robust model is validated via experimental tests and machining. Experimental results show that thermal displacement variations are controlled within 2 μm when the compensation system is activated. The suggested model can achieve high accuracy and good applicability in different moving states. Machining results indicate that dimensional accuracy of the workpiece is significantly improved after implementation of compensation. Feasibility of the thermal error compensation system is satisfactory in applications for drilling operations.
A Robust Multi-Circle Detector Based on Horizontal and Vertical Search Analysis Fitting with Tangent Direction
Authors: Li Shaodong , Du Zhijiang , Yu Hongjian , Yi Jiafu 
Published: August 2018

In this paper, we propose an efficient Multi-Circle detector which follows the fixed search order. The method makes use of horizontal and vertical search to realize circle detection, which is named as HVCD. First, this method computes edge areas in a given image. The edge areas could be divided into some regions by means of region growing. Each of regions could be efficiently searched to achieve not only one-pixel wide edges but edge segments as well. Next, the candidate circles can be extracted from every edge segment. Finally, the circle candidates could be validated with the help of Helmholtz principle. Experimental results demonstrate that HVCD could effectively detect circles on synthetic and natural images on the one hand; on the other hand, HVCD here could solve the weakness in the process of circle Hough transform implementation and EDcircles implementation.
Mineralocorticoid receptor antagonism improves parenchymal arteriole dilation via a TRPV4-dependent mechanism and prevents cognitive dysfunction in hypertension
Authors: Diaz-Otero Janice M. , Yen Ting-Chieh , Fisher Courtney , Bota Daniel , Jackson William F. , Dorrance Anne M. 
Published: August 2018

Hypertension and mineralocorticoid receptor activation cause cerebral parenchymal arteriole remodeling; this can limit cerebral perfusion and contribute to cognitive dysfunction. We used a mouse model of angiotensin II-induced hypertension to test the hypothesis that mineralocorticoid receptor activation impairs both transient receptor potential vanilloid (TRPV)4-mediated dilation of cerebral parenchymal arterioles and cognitive function. Mice (16−18 wk old, male, C57Bl/6) were treated with angiotensin II (800 ng·kg−1·min−1) with or without the mineralocorticoid receptor antagonist eplerenone (100 mg·kg−1·day−1) for 4 wk; sham mice served as controls. Data are presented as means ± SE; n = 5–14 mice/group. Eplerenone prevented the increased parenchymal arteriole myogenic tone and impaired carbachol-induced (10−9–10−5 mol/l) dilation observed during hypertension. The carbachol-induced dilation was endothelium-derived hyperpolarization mediated because it could not be blocked by N-nitro-l-arginine methyl ester (10−5 mol/l) and indomethacin (10−4 mol/l). We used GSK2193874 (10−7 mol/l) to confirm that in all groups this dilation was dependent on TRPV4 activation. Dilation in response to the TRPV4 agonist GSK1016790A (10−9–10−5 mol/l) was also reduced in hypertensive mice, and this defect was corrected by eplerenone. In hypertensive and eplerenone-treated animals, TRPV4 inhibition reduced myogenic tone, an effect that was not observed in arterioles from control animals. Eplerenone treatment also improved cognitive function and reduced microglia density in hypertensive mice. These data suggest that the mineralocorticoid receptor is a potential therapeutic target to improve cerebrovascular function and cognition during hypertension. NEW & NOTEWORTHY Vascular dementia is a growing public health issue that lacks effective treatments. Transient receptor potential vanilloid (TRPV)4 channels are important regulators of parenchymal arteriole dilation, and they modulate myogenic tone. The data presented here suggest that TRPV4 channel expression is regulated by the mineralocorticoid receptor (MR). MR blockade also improves cognitive function during hypertension. MR blockade might be a potential therapeutic approach to improve cerebrovascular function and cognition in patients with hypertension.
Attenuated forearm vascular conductance responses to rhythmic handgrip in young African-American compared with Caucasian-American men
Authors: Barbosa Thales C. , Kaur Jasdeep , Stephens Brandi Y. , Akins John D. , Keller David M. , Brothers R. Matthew , Fadel Paul J. 
Published: August 2018

Previous studies have demonstrated that African-American (AA) individuals have heightened vasoconstrictor and reduced vasodilator responses under resting conditions compared with Caucasian-American (CA) individuals. However, potential differences in vascular responses to exercise remain unclear. Therefore, we tested the hypothesis that, compared with CA subjects, AA subjects would present an attenuated increase in forearm vascular conductance (FVC) during rhythmic handgrip exercise. Forearm blood flow (FBF; duplex Doppler ultrasound) and mean arterial pressure (MAP; finger photoplethysmography) were measured in healthy young CA ( n = 10) and AA ( n = 10) men during six trials of rhythmic handgrip performed at workloads of 4, 8, 12, 16, 20, and 24 kg. FVC (calculated as FBF/MAP), FBF, and MAP were similar between groups at rest (FVC: 63 ± 7 ml·min−1·100 mmHg−1 in CA subjects vs. 62 ± 7 ml·min−1·100 mmHg−1 in AA subjects, P = 0.862). There was an intensity-dependent increase in FVC during exercise in both groups; however, AA subjects presented lower FVC (interaction P < 0.001) at 8-, 12-, 16-, 20-, and 24-kg workloads (e.g., 24 kg: 324 ± 20 ml·min−1·100 mmHg−1 in CA subjects vs. 241 ± 21 ml·min−1·100 mmHg−1 in AA subjects, P < 0.001). FBF responses to exercise were also lower in AA subjects (interaction P < 0.001), whereas MAP responses did not differ between groups (e.g., ∆MAP at 24 kg: +19 ± 2 mmHg in CA subjects vs. +19 ± 2 mmHg in AA subjects, interaction P = 0.950). These findings indicate lower hyperemic responses to rhythmic handgrip exercise in AA men compared with CA men. NEW & NOTEWORTHY It is known that African-American individuals have heightened vasoconstriction and reduced vasodilation under resting conditions compared with Caucasian-American individuals. Here, we identified that the hyperemic response to moderate and high-intensity rhythmic handgrip exercise was lower in healthy young African-American men.
Abstract A067: Salinomycin kills not only circulating epithelial tumor cells (CETCs) but also circulating cancer stem cells (cCSC) and may potentially prevent progression in patients with breast cancer
Authors: Pizon Monika , Schott Dorothea , Pachmann Ulrich , Pachmann Katharina , Szalus Norbert 
Published: August 2018

Abstract
Background: Recently the hypothesis has been proposed that a more aggressive subpopulation of circulating tumor cells, circulating cancer stem cells, are the source of metastatic spread from the primary tumor. These cells are considered to be responsible for treatment relapse and have therefore become a major target in cancer research. The antibiotic salinomycin isolated from Streptomyces albus is the best established cancer stem cell inhibitor and has been shown to reduce the expression of markers for stemness and spheroid-forming ability. The mechanisms of the anticancer effects remain unclear. In this study, we evaluated the cytotoxic effect of salinomycin on CETCs and tumorspheres cultured from cCSC. Methods: 20 patients with breast cancer in different stages of disease were included. The determination of CETCs and cCSC was performed using Maintrac® method and tumorsphere forming assay, respectively. To evaluate the cytotoxic effect of salinomycin on CETCs and spheroids, they were exposed to different concentrations of salinomycin in short time culture for different periods of time. Results: 79% of patients had detectable CETCs and sphere formation was observed in 74% of breast cancer patients. Interestingly, growth of spheroids was detected also in patients without CETCs. The number of tumorspheres increased significantly with tumor progression, especially with presence of metastasis. Treatment with salinomycin showed an 80% reduction in spheroid formation compared with control. Salinomycin reduced the viability of spheroids in a dose-dependent manner. Salinomycin had a stronger cytotoxic effect on CETCs in nonmetastatic as compared to metastatic patients (median of dead CETCs 85% vs. 34%, p&lt;0.001). Similarly, patients without chemotherapy responded better to salinomycin treatment than patients after several lines of chemotherapy (median of dead CETCs 87%vs.35%, p&lt;0.001). Conclusion: Using a method for cultivation of tumorspheres from peripheral blood of cancer patients and an effective in vitro platform for screening anticancer stem cells drugs was developed. Thus it could be shown that salinomycin targets not only more differentiated circulating cancer cells but also cancer stem cells from peripheral blood. It may evolve as a novel and promising therapeutic strategy for future cancer treatment.
Citation Format: Monika Pizon, Dorothea Schott, Ulrich Pachmann, Katharina Pachmann, Norbert Szalus. Salinomycin kills not only circulating epithelial tumor cells (CETCs) but also circulating cancer stem cells (cCSC) and may potentially prevent progression in patients with breast cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A067.
Abstract A131: Comparison of next-generation sequencing results between brain metastasis and blood in NSCLC patients with acquired EGFR-TKI resistance other than T790M mutation
Authors: Lee Hee Yeon , Kim Jeong-Oh , Kang Jin-Hyoung 
Published: August 2018

Abstract
Background: Mechanisms of acquired resistance for EGFR tyrosine kinase inhibitor (TKI) in non-small cell lung cancer (NSCLC) has been studied broadly, and T790M mutation, bypass signaling, and phenotype change have been suggested. Questions remain in terms of the selection of sub-clones according to the sites during EGFR TKI therapy, especially in brain due to blood-brain barrier. Three metastatic NSCLC patients harboring sensitive EGFR mutation were treated with EGFT TKI with good response but became refractory and symptomatic brain oligo-metastasis occurred. Metastectomy was done and next-generation sequencing (NGS) was done with the brain tissue and blood. Methods: Fresh brain metastasis tissue was obtained during surgery and frozen in liquid nitrogen. Blood sampling was done within a week of the surgery and plasma was used for NGS. Amplicon sequencing (Thunderbolt) was performed. Library preparation and quality control sequencing amplicon libraries were prepared using ThunderBolts Cancer Panel, according to the manufacturer's instructions. The ThunderBolts Cancer Panel uses 230 amplicons to interrogate mutations and hotspots in 50 oncogenes, tumor suppressors, and drug resistance markers. Results: All 3 brain tissues had the same sensitive EGFR mutation (exon 19 deletion) as initial presentation, with PDGFRA, APC and TP53 mutations, while in the plasma, PDGFRA and APC mutations were identified in the 3 patients. From case 1, PDGFRA, APC, MLH1, and EGFR mutations were identified in the plasma, and additional PIK3CA, KDR, TP53, ERBB2, and GNA11 mutations were found in the brain. From case 2, PDGFRA, APC, EGFR, MET, PTEN, HRAS, and TP53 mutations were found in the plasma, and in the brain, PIK3CA, KDR, and ERBB2 mutations were identified in addition. From case 3, PDGFRA, APC, HRAS, and TP53 mutations in the plasma, and additional EGFR mutation in the brain. Conclusions: Our data identified several additional mutations in brain metastasis compared to the plasma from patients with acquired EGFR TKI resistance, other than T790M mutation. Every mutation in the blood sample was identified in the brain tissue, while additional mutations were found in the brain tissue.
Citation Format: Hee Yeon Lee, Jeong-Oh Kim, Jin-Hyoung Kang. Comparison of next-generation sequencing results between brain metastasis and blood in NSCLC patients with acquired EGFR-TKI resistance other than T790M mutation [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A131.