bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined use of principal component analysis and random forests identify population‐informative single nucleotide polymorphisms: application in cattle breeds
Authors: Bertolini F. , Galimberti G. , Calò D.G. , Schiavo G. , Matassino D. , Fontanesi L. 
Published: March 2015

SummaryThe genetic identification of the population of origin of individuals, including animals, has several practical applications in forensics, evolution, conservation genetics, breeding and authentication of animal products. Commercial high‐density single nucleotide polymorphism (SNP) genotyping tools that have been recently developed in many species provide information from a large number of polymorphic sites that can be used to identify population‐/breed‐informative markers. In this study, starting from Illumina BovineSNP50 v1 BeadChip array genotyping data available from 3711 cattle of four breeds (2091 Italian Holstein, 738 Italian Brown, 475 Italian Simmental and 407 Marchigiana), principal component analysis (PCA) and random forests (RFs) were combined to identify informative SNP panels useful for cattle breed identification. From a PCA preselected list of 580 SNPs, RFs were computed using ranking methods (Mean Decrease in the Gini Index and Mean Accuracy Decrease) to identify the most informative 48 and 96 SNPs for breed assignment. The out‐of‐bag (OOB) error rate for both ranking methods and SNP densities ranged from 0.0 to 0.1% in the reference population. Application of this approach in a test population (10% of individuals pre‐extracted from the whole data set) achieved 100% of correct assignment with both classifiers. Linkage disequilibrium between selected SNPs was relevant (r2 > 0.6) only in few pairs of markers indicating that most of the selected SNPs captured different fractions of variance. Several informative SNPs were in genes/QTL regions that affect or are associated with phenotypes or production traits that might differentiate the investigated breeds. The combination of PCA and RF to perform SNP selection and breed assignment can be easily implemented and is able to identify subsets of informative SNPs useful for population assignment starting from a large number of markers derived by high‐throughput genotyping platforms.
Relation Between Left Atrial Wall Thickness in Patients with Atrial Fibrillation and Intracardiac Electrogram Characteristics and ATP‐Provoked Dormant Pulmonary Vein Conduction
Authors: TAKAHASHI KEIKO , OKUMURA YASUO , WATANABE ICHIRO , NAGASHIMA KOICHI , SONODA KAZUMASA , SASAKI NAOKO , KOGAWA RIKITAKE , ISO KAZUKI , OHKUBO KIMIE , NAKAI TOSHIKO , HIRAYAMA ATSUSHI 
Published: March 2015

LA Wall Thickness, LA Electrogram, and Dormant PV ConductionIntroductionAtrial remodeling plays a key role in development of the substrate for atrial fibrillation (AF). Whether the wall thicknesses of the left atrium (LA) and pulmonary vein (PV)–LA junction affect remodeling and AF ablation is unknown. We investigated the relationship between wall thicknesses, electrogram characteristics, and adenosine triphosphate (ATP)‐provoked dormant PV conduction as they pertain to AF.MethodsIn 50 patients with AF and 25 patients without AF, wall thicknesses of the LA and PV–LA junction were measured on 320‐slice computed tomography images. For the AF patients, NavX‐based voltage maps generated during sinus rhythm were obtained, and ATP‐provoked dormant PV conduction after PV isolation was evaluated.ResultsWalls of the LA and PV–LA junction were significantly thicker in the AF patients than in the control patients (1.83 ± 0.29 mm vs. 1.59 ± 0.28 mm, respectively; P = 0.0010; and 0.88 ± 0.14 mm vs. 0.65 ± 0.11 mm, P<0.0001, respectively). Wall thickness at the PV–LA junction was independently associated with AF (β = 0.40, P = 0.0002). In AF patients, the walls of the PV–LA junction showed stepwise thickening across bipolar voltages indicative of severe (bipolar voltage <33rd percentile) to moderate (33rd–66th percentiles) to mild fibrosis/scarring (≥66th percentile). Walls of the PV–LA junction with dormant PV conduction were significantly thicker than those without it (0.94 ± 0.19 mm vs. 0.86 ± 0.21 mm, respectively; P = 0.0025).ConclusionsTogether, the association between thickened PV–LA junction walls and AF and the increased bipolar voltage suggests that such wall thickening increases PV electrical activities, leading to initiation and maintenance of AF and perhaps to ATP‐provoked dormant PV conduction.
Antioxidant icariside II combined with insulin restores erectile function in streptozotocin‐induced type 1 diabetic rats
Authors: Wang Lin , Xu Yongde , Li Huixi , Lei Hongen , Guan Ruili , Gao Zhezhu , Xin Zhongcheng 
Published: March 2015

AbstractErectile dysfunction (ED) worsens in patients with diabetes mellitus (DM) despite good control of blood glucose level with insulin. Recent studies imply that diabetic vascular stresses (e.g. oxidative stress) persist in spite of glucose normalization, which is defined as metabolic memory. Studies suggest that the interaction between advanced glycation end products (AGEs) and their receptor (RAGE) mediates the development of metabolic memory. To investigate the effects of the antioxidant icariside II plus insulin on erectile function in streptozotocin (STZ)‐ induced type 1 diabetic rats. Fifty 8‐week‐old Sprague‐Dawley rats were randomly distributed into five groups: normal control, diabetic, insulin‐treated diabetic, icariside II‐treated diabetic, and insulin plus icariside II‐treated diabetic. Diabetes was induced by a single intraperitoneal injection of STZ. Eight weeks after induction of diabetes, icariside II was administered by gastric lavage once a day (5 mg/kg) for 6 weeks; and 2–6 units of intermediate‐acting insulin were given to maintain normal glycemia for 6 weeks. The main outcome measures were the ratio of intracavernous pressure (ICP) to mean arterial pressure (MAP); histology of penile endothelial cells and smooth muscle cells; neural nitric oxide synthase, AGEs and RAGE expression; malondialdehyde concentration; superoxide dismutase activity; and apoptosis index. Diabetic rats demonstrated a significantly lower ICP/MAP ratio, reduced penile endothelial cells, reduced smooth muscle cells, increased AGEs and RAGE, and increased apoptosis. Insulin and icariside II monotherapy partially restored erectile function and histological changes. However, the combination therapy group showed significantly better erectile parameters, cytological components and biochemistry, similar to those in the normal control group. These results suggest that, although insulin can effectively control glycemic levels, it does not completely alter the pathological changes in erectile tissues. Better efficacy could be expected with tight glycemic control plus the antioxidant icariside II. The proposed combination therapy might have the potential to eliminate metabolic memory by down‐regulating the AGEs‐RAGE‐oxidative stress axis.
Controlled aggregation of primary human pancreatic islet cells leads to glucose‐responsive pseudoislets comparable to native islets
Authors: Hilderink Janneke , Spijker Siebe , Carlotti Françoise , Lange Lydia , Engelse Marten , van Blitterswijk Clemens , de Koning Eelco , Karperien Marcel , van Apeldoorn Aart 
Published: March 2015

AbstractClinical islet transplantation is a promising treatment for patients with type 1 diabetes. However, pancreatic islets vary in size and shape affecting their survival and function after transplantation because of mass transport limitations. To reduce diffusion restrictions and improve islet cell survival, the generation of islets with optimal dimensions by dispersion followed by reassembly of islet cells, can help limit the length of diffusion pathways. This study describes a microwell platform that supports the controlled and reproducible production of three‐dimensional pancreatic cell clusters of human donor islets. We observed that primary human islet cell aggregates with a diameter of 100–150 μm consisting of about 1000 cells best resembled intact pancreatic islets as they showed low apoptotic cell death (<2%), comparable glucose‐responsiveness and increasing PDX1, MAFA and INSULIN gene expression with increasing aggregate size. The re‐associated human islet cells showed an a‐typical core shell configuration with beta cells predominantly on the outside unlike human islets, which became more randomized after implantation similar to native human islets. After transplantation of these islet cell aggregates under the kidney capsule of immunodeficient mice, human C‐peptide was detected in the serum indicating that beta cells retained their endocrine function similar to human islets. The agarose microwell platform was shown to be an easy and very reproducible method to aggregate pancreatic islet cells with high accuracy providing a reliable tool to study cell–cell interactions between insuloma and/or primary islet cells.
High‐fat diet induces cardiac remodelling and dysfunction: assessment of the role played by SIRT3 loss
Authors: Zeng Heng , Vaka Venkata Ramana , He Xiaochen , Booz George W. , Chen Jian‐Xiong 
Published: March 2015

AbstractMitochondrial dysfunction plays an important role in obesity‐induced cardiac impairment. SIRT3 is a mitochondrial protein associated with increased human life span and metabolism. This study investigated the functional role of SIRT3 in obesity‐induced cardiac dysfunction. Wild‐type (WT) and SIRT3 knockout (KO) mice were fed a normal diet (ND) or high‐fat diet (HFD) for 16 weeks. Body weight, fasting glucose levels, reactive oxygen species (ROS) levels, myocardial capillary density, cardiac function and expression of hypoxia‐inducible factor (HIF)‐1α/‐2α were assessed. HFD resulted in a significant reduction in SIRT3 expression in the heart. Both HFD and SIRT3 KO mice showed increased ROS formation, impaired HIF signalling and reduced capillary density in the heart. HFD induced cardiac hypertrophy and impaired cardiac function. SIRT3 KO mice fed HFD showed greater ROS production and a further reduction in cardiac function compared to SIRT3 KO mice on ND. Thus, the adverse effects of HFD on cardiac function were not attributable to SIRT3 loss alone. However, HFD did not further reduce capillary density in SIRT3 KO hearts, implicating SIRT3 loss in HFD‐induced capillary rarefaction. Our study demonstrates the importance of SIRT3 in preserving heart function and capillary density in the setting of obesity. Thus, SIRT3 may be a potential therapeutic target for obesity‐induced heart failure.
Insulin combined with Chinese medicine improves glycemic outcome through multiple pathways in patients with type 2 diabetes mellitus
Authors: Zhang Xinxia , Liu Ya , Xiong Daqian , Xie Chunguang 
Published: March 2015

AbstractIntroduction/AimsInsufficient insulin secretion or inefficient insulin response are responsible for the clinical outcome of type 2 diabetes mellitus. Administration of insulin alone is prone to cause secondary effects, resulting in an unsatisfactory outcome. Shen‐Qi‐Formula (SQF), a well‐known Chinese medicinal formula, has been used for diabetic treatment for a long time. The present study was designed to investigate whether SQF in combination with insulin improved the clinical outcome of type 2 diabetes mellitus, and what mechanisms were possibly involved in the treatment.Materials and MethodsA total of 219 patients were included in the study. Of these, 110 patients were treated with insulin monotherapy, and 109 with the combination therapy of SQF and insulin. Before and after 12‐week treatment, the fasting blood glucose, postprandial blood glucose, β‐cell function, insulin resistance and blood lipids were measured.ResultsThe 12 weeks of SQF treatment in combination with insulin significantly decreased the fasting and postprandial blood glucose levels. Insulin secretion was not increased after the treatment, but β‐cell function and insulin resistance were obviously improved. Furthermore, 12 weeks of treatment with SQF and insulin improved the levels of glucagon‐like peptide‐1, oxidative stress, blood lipids, coagulation function and bodyweight.ConclusionThe results from our study showed that the combination therapy of SQF and insulin significantly improved the clinical outcome of type 2 diabetes mellitus compared with insulin monotherapy. The mechanism of improvement was possibly involved in the multiple pathways.
Predictability of 1‐h postload plasma glucose concentration: A 10‐year retrospective cohort study
Authors: Kuang Lifen , Huang Zhimin , Hong Zhenzhen , Chen Ailing , Li Yanbing 
Published: March 2015

AbstractAims/IntroductionElevated 1‐h postload plasma glucose concentration (1hPG) during oral glucose tolerance test has been linked to an increased risk of type 2 diabetes and a poorer cardiometabolic risk profile. The present study analyzed the predictability and cut‐off point of 1hPG in predicting type 2 diabetes in normal glucose regulation (NGR) subjects, and evaluated the long‐term prognosis of NGR subjects with elevated 1hPG in glucose metabolism, kidney function, metabolic states and atherosclerosis.Materials and MethodsA total of 116 Han Chinese classified as NGR in 2002 at the First Affiliated Hospital of Sun Yat‐sen University, Guangzhou, Guangdong, China, were investigated. Follow‐up was carried out in 2012 to evaluate the progression of glucose metabolism, kidney function, metabolic syndrome and carotid atherosclerosis.ResultsThe areas under receiver operating characteristic curves were higher for 1hPG than FPG or 2hPG (0.858 vs 0.806 vs 0.746). The cut‐off value of 1hPG with the maximal sum of sensitivity and specificity in predicting type 2 diabetes in NGR subjects was 8.85 mmol/L. The accumulative incidence of type 2 diabetes in subjects with 1hPG ≥8.85 mmol/L was higher than those <8.85 mmol/L (46.2% vs 3.3%, P = 0.000; relative risk 13.846, 95% confidence interval 4.223–45.400). On follow up, the prevalence of metabolic syndrome and abnormal carotid intima‐media thickness in the subjects with 1hPG ≥8.85 mmol/L tended to be higher compared with those <8.85 mmol/L.Conclusions1hPG is a good predictor of type 2 diabetes in NGR subjects, and the best cut‐off point is 8.85 mmol/L. Some tendency indicates that NGR subjects with 1hPG ≥8.85 mmol/L are more prone to metabolic syndrome and carotid atherosclerosis.
The Development of a Consensus Statement on Normal Physiologic Birth: A Modified Delphi Study
Authors: Kennedy Holly Powell , Cheyney Melissa , Lawlor Mary , Myers Suzy , Schuiling Kerri , Tanner Tanya 
Published: March 2015

IntroductionThis article describes the process of developing consensus on a definition of, and best practices for, normal physiologic birth in the United States. Evidence supports the use of physiologic birth practices, yet a working definition of this term has been elusive.MethodsWe began by convening a task force of 21 individuals from 3 midwifery organizations and various childbirth advocacy and consumer groups. A modified Delphi approach was utilized to achieve consensus around 2 research questions: 1) What is normal physiologic birth? and 2) What practices most effectively support its achievement? Answers to these questions were collected anonymously from task force members during multiple phases that included a preliminary briefing, an initial face‐to‐face roundtable, 9 iterative Delphi rounds, and reciprocal feedback from a wider audience of stakeholders at national and international conferences. Content analysis identified specific statements and concepts in the first Delphi round, which were subsequently ranked in following rounds. An initial draft was constructed based on the priorities that emerged and presented for feedback to peers and childbirth advocates whose comments were incorporated into the final document.ResultsFour key themes were identified from our initial questions; these provided the framework for the document: 1) definitions of normal physiologic birth, 2) mechanisms and outcomes of normal physiologic birth, 3) factors that influence normal physiologic birth, and 4) recommendations for increasing normal physiologic birth. These areas comprised the final sections in the multi‐organizational consensus statement.DiscussionThe modified Delphi approach we employed allowed for the development of a consensus statement that will serve as a template for education, practice, and future research in maternity care. The completion of this statement marks the beginning of a project to promote systemic changes that support normal physiologic birth, and thus, have the potential to improve outcomes for mothers and infants.
Regulation of adipogenesis and osteogenesis in mesenchymal stem cells by vascular endothelial growth factor A
Authors: Berendsen A. D. , Olsen B. R. 
Published: March 2015

AbstractUnderstanding the mechanisms by which bone marrow mesenchymal stem cells (BMSCs) differentiate into bone‐forming osteoblasts and marrow adipocytes is crucial to develop strategies for the treatment of several bone diseases. Age‐related bone loss resulting in osteopenia and osteoporosis has been associated with reduced numbers of osteoblasts and increased numbers of adipocytes, likely originating from differentiation defects in BMSCs. Although many factors involved in the complex regulation of osteoblast and adipocyte cell lineages have previously been identified, their functional interactions in the context of BMSC differentiation and maintenance of bone homeostasis during ageing are unknown. Recent discoveries have provided important new insights into the mechanisms by which the nuclear envelope protein lamin A and vascular endothelial growth factor A (VEGF) mutually control BMSC fate. Particularly interesting is the finding that VEGF in this context functions as an intracellular protein, unaffected by neutralizing antibodies, and not as a secreted growth factor. These insights may not only facilitate the identification of new targets for treating bone diseases but also lead to improved design of tissue engineering approaches aimed at stimulating bone regeneration and repair.
SURVEY OF STAFF OPINIONS ABOUT EXTENDED HAEMODIALYSIS TREATMENT TIME AND SERVICE IMPLICATIONS
Authors: Singh Seema , Procter Susan , Power Albert , Pusey Charles , Choi Peter , Duncan Neill , Brown Edwina 
Published: March 2015

SUMMARYBackgroundWe explored the potential impact of staff opinions and service provision upon patient's willingness to recruit to a clinical trial studying the effects of extended treatment time (TT) on haemodialysis (HD), six hours versus four hours for a period of twenty‐four weeks.MethodsWe conducted a local survey of dialysis nurses and a national survey of multidisciplinary HD staff opinions to extended TT including clinical benefits, tolerance to, prescription and ability to accommodate extended TT on in‐centre HD programmes.ResultsThe survey was completed by 56/134 (42%) local nurses and the national survey by 15/72 (21%) of dialysis providers across the UK (35% nurses and 75% other healthcare professionals). The majority of respondents felt extended TT was clinically beneficial but only 42% of nurses would recommend extended TT compared to 95% of non‐nursing healthcare professionals (p < 0.0001). Although 45% of nurses felt that it was well tolerated, non‐nursing healthcare professionals suggested this was significantly higher at 75% (p < 0.05). The negative impact on service provision was agreed by 83% of nurses with the need to facilitate shifts within a finite time period and pressure to find session spaces being cited.ConclusionThere is conflict between the understanding that extended TT is clinically beneficial and its prescription & delivery to patients. Enrolment to studies examining HD delivery strategies may be influenced by service provision and staff attitudes. In centre HD has been designed to maximise patient throughput and we may need to consider more flexible settings in which to deliver longer treatment time: Home HD maybe a solution.
OIL CHARGE HISTORY OF BITUMENS OF DIFFERING MATURITIES IN EXHUMED PALAEOZOIC RESERVOIR ROCKS AT TIANJINGSHAN, NW SICHUAN BASIN, SOUTHERN CHINA
Authors: Zhou Q. , Xiao X.M. , Tian H. , Wilkins R. W. T. 
Published: March 2015

Low‐maturity soft bitumen (or biodegraded heavy oil) and higher maturity solid bitumen are present in Palaeozoic siliciclastics at Tianjingshan in the NW Sichuan Basin, southern China. The origin of these bitumens of variable maturities was investigated. Samples of low‐maturity bitumen from Lower Devonian sandstones and high‐ and low‐maturity bitumen from Upper Cambrian siltstones were analysed to investigate their organic geochemistry and stable isotope compositions. Lower Cambrian and Upper Permian black shales were also investigated to assess their source rock potential, and the burial and maturation history of potential source rocks was modelled using PetroMod. Liquid and gaseous hydrocarbon fluid inclusions in the Devonian sandstones were analysed.Results suggest that both the soft and solid bitumens are derived from crude oil generated by Lower Cambrian organic‐rich black shales. Reservoir rocks at Tianjingshan have experienced two separate oil charge events – in the early‐middle Triassic and early‐middle Jurassic, respectively. The first oil charge was generated by Lower Cambrian black shales in a kitchen area located in the hanging wall of the Tianjingshan fault. The later oil charge was also derived from Lower Cambrian black shales, but the kitchen area was located in the footwall of the fault. Movement on the Tianjingshan fault resulted in progressive burial of the Lower Devonian sandstone reservoir rocks until the end of the middle Triassic, and the “early” charged oil was thermally degraded into high‐maturity solid bitumen. The later‐charged oil was altered into soft bitumen of lower maturiy by biodegradation during uplift of the reservoir after the Jurassic.
Chloroplastic and cytoplasmic overexpression of sheep serotonin N‐acetyltransferase in transgenic rice plants is associated with low melatonin production despite high enzyme activity
Authors: Byeon Yeong , Lee Hyoung Yool , Back Kyoungwhan 
Published: March 2015

AbstractSerotonin N‐acetyltransferase (SNAT), the penultimate enzyme in melatonin biosynthesis, catalyzes the conversion of serotonin into N‐acetylserotonin. Plant SNAT is localized in chloroplasts. To test SNAT localization effects on melatonin synthesis, we generated transgenic rice plants overexpressing a sheep (Ovis aries) SNAT (OaSNAT) in their chloroplasts and compared melatonin biosynthesis with that of transgenic rice plants overexpressing OaSNAT in their cytoplasm. To localize the OaSNAT in chloroplasts, we used a chloroplast targeting sequence (CTS) from tobacco protoporphyrinogen IX oxidase (PPO), which expresses in chloroplasts. The purified recombinant CTS:OaSNAT fusion protein was enzymatically functional and localized in chloroplasts as confirmed by confocal microscopic analysis. The chloroplast‐targeted CTS:OaSNAT lines and cytoplasm‐expressed OaSNAT lines had similarly high SNAT enzyme activities. However, after cadmium and butafenacil treatments, melatonin production in rice leaves was severalfold lower in the CTS:OaSNAT lines than in the OaSNAT lines. Notably, enhanced SNAT enzyme activity was not directly proportional to the production of N‐acetylserotonin, melatonin, or 2‐hydroxymelatonin, suggesting that plant SNAT has a role in the homeostatic regulation of melatonin rather than in accelerating melatonin synthesis.