bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aspirin responsiveness changes in obese patients following bariatric surgery
Authors: Norgard Nicholas B. , Monte Scott V. , Fernandez Stanley F. , Ma Qing 
Published: April 2017

SummaryAimsBariatric surgery has emerged as a promising treatment option for weight loss and to counter the metabolic consequences of obesity. Obesity has been linked to a hyperaggregable state, as well as a blunted response to aspirin. This pilot study assessed the hypothesis that bariatric surgery would lead to an improvement in aspirin‐induced platelet inhibition and a reduction in platelet aggregability.MethodsFifteen patients scheduled to undergo bariatric surgery were administered two 7‐day courses of aspirin 81 mg: the first course administered before surgery and the second was 3 months following surgery. Platelet aggregation was measured before and after each aspirin course using VerifyNow‐Aspirin. The primary endpoint was the change in on‐treatment aspirin reactive units (ARU) pre‐ and postsurgery. Data from bariatric surgery study patients were compared to data of normal weighted subjects gathered in a previous study.ResultsRoux‐en‐Y gastric bypass was performed in 80%, and 20% underwent sleeve gastrectomy. The mean starting body mass index (BMI) was 46.9 kg/m2. Patients lost on average 24.5 kg, resulting in a postsurgical BMI of 38.5 kg/m2. Postbariatric surgery, off‐treatment ARU was significantly reduced from presurgery levels (602±59 vs 531±78; P=.035). On‐aspirin platelet reactivity was also significantly reduced following surgery (469±60 vs 432±143, P=.03). There was a significant correlation between the extent of weight loss and the degree of improvement in on‐aspirin platelet reactivity (r2=.49, P=.024). Presurgery on‐aspirin platelet reactivity was significantly higher in obese patients compared to normal weighted subjects (469±60 vs 419±52; P=.016) and reduced to the baseline after the surgery (432±63 vs 419±52; P=.54).ConclusionAspirin‐induced platelet inhibition may be more potent following bariatric surgery. The mechanisms behind this improvement require further investigation.
New Apatite Fission‐Track Ages of the Western Kuqa Depression: Implications for the Mesozoic–Cenozoic Tectonic Evolution of South Tianshan, Xinjiang
Authors: YANG Wei , LI Jianfeng , GUO Zhaojie , JOLIVET Marc , HEILBRONN Gloria 
Published: April 2017

AbstractThe Mesozoic–Cenozoic uplift history of South Tianshan has been reconstructed in many ways using thermochronological analyses for the rocks from the eastern Kuqa Depression. The main difference in the reconstructions concerns the existence and importance of Early Cretaceous and Paleogene tectonic activities, but the existence of a Cenozoic differential uplift in the Kuqa Depression remains enigmatic. Here, we present new apatite fission‐track ages obtained for 12 sandstone samples from the well‐exposed Early Triassic to Quaternary sequence of the Kapushaliang section in the western Kuqa Depression. The results reveal that there were four pulses of tectonic exhumation, which occurred during the Early Cretaceous (peak ages of 112 and 105 Ma), Late Cretaceous (peak age of 67 Ma), Paleocene–Eocene (peak ages at 60, 53, and 36 Ma), and early Oligocene to late Miocene (central ages spanning 30–11 Ma and peak ages of 23 and 14 Ma), respectively. A review of geochronological and geological evidence from both the western and eastern Kuqa Depression is shown as follows. (1) The major exhumation of South TiansShan during the Early Cretaceous was possibly associated with docking of the Lhasa block with the southern margin of the Eurasian plate. (2) The Late Cretaceous uplift of the range occurred diachronically due to the far‐field effects of the Kohistan‐Dras Arc and Lhasa block accretion. (3) The Paleogene uplift in South Tianshan initially corresponded to the far‐field effects of the India–Eurasia collision. (4) The rapid exhumation in late Cenozoic was driven by the continuous far‐field effects of the collision between India and Eurasia plates. The apatite fission‐track ages of 14–11 Ma suggest that late Cenozoic exhumation in the western Kuqa Depression prevailed during the middle to late Miocene, markedly later than the late Oligocene to early Miocene activity in the eastern segment. It can be hypothesized that a possible differential uplift in time occurred in the Kuqa Depression during the late Cenozoic.
Hydrochemistry and H‐O‐C‐S Isotopic Geochemistry Characteristics of Geothermal Water in Nyemo‐Nagqu, Tibet
Authors: WANG Siqi , LIU Zhao , SHAO Jingli 
Published: April 2017

AbstractNyemo‐Nagqu, Tibet, is rich in high‐temperature geothermal resources. The geothermal fields in Yangbajain and Yangyi as well as 11 unexplored geothermal fields along the geothermal belt from Nyemo to Nagqu were systematically investigated and the hydrochemistry data were collected from the whole field. Meanwhile, H‐O‐C‐S isotope data were obtained for the new fields, and H‐O isotope data for the Yangbajain and Yangyi fields. A comparison of the Nyemo‐Nagqu geothermal fields with those in the Yangbajain area shows that the types of high‐temperature geothermal water are dominated by Cl‐Na and Cl·HCO3‐Na, while the types of medium‐high‐temperature geothermal water are dominated by HCO3‐Na. The concentrations of Li, F, SiO2, and HBO2 in the geothermal water are positively correlated with Cl content, indicating possible mixing with magma water. The reservoir temperatures range from 90 to 270°C by geothermometers. Slight drifting of 18O was recorded at the Dongweng and Nyingzhong high‐temperature geothermal fields, while more significant drifting was recorded at Gulu. The geothermal water is mainly replenished by atmospheric precipitation. The low tritium contents (<1 TU) of the geothermal water from Nyingzhong, Gulu, and Luoma indicate that it is mainly replenished by sub‐modern (prior to 1952) water, while the high tritium content (8.4 TU) in Yuela implies modern water replenishment. Other geothermal fields are replenished by a mix of sub‐modern fresher water. The isotopic data in this study show that the carbon and sulfur in the geothermal water originates mainly from sediment leaching, with some of the carbon and sulfur having a deep origin.
Germanium in Magnetite: A Preliminary Review
Authors: MENG Yumiao , HU Ruizhong , HUANG Xiaowen , GAO Jianfeng 
Published: April 2017

AbstractMagnetite is a very common mineral in various types of iron deposits and some sulfide deposits. Recent studies have focused on the use of trace elements in magnetite to discriminate ore types or trace ore‐forming process. Germanium is a disperse element in the crust, but sometimes is not rare in magnetite. Germanium in magnetite can be determined by laser ablation ICP‐MS due to its low detection limit (0.0X ppm). In this study, we summary the Ge data of magnetite from magmatic deposits, iron formations, skarn deposits, iron oxide copper‐gold deposits, and igneous derived hydrothermal deposits. Magnetite from iron formations contains relatively high Ge (up to ∼250 ppm), whereas those from all other deposits mostly contains Ge less than 10 ppm, indicating that iron formations can be discriminated from other Fe deposits by Ge contents. Germanium in magmatic/hydrothermal magnetite is controlled by a few factors. Primary magma/fluid composition may be the major control of Ge in magnetite. Higher oxygen fugacity may be beneficial to Ge partition into magnetite. Sulfur fugacity and temperature may have little effect on Ge in magnetite. The enrichment mechanism of Ge in magnetite from iron formations remains unknown due to the complex ore genesis. Germanium along with other elements (Mn, Ni, Ga) and element ratios (Ge/Ga and Ge/Si raios) can distinguish different types of deposits, indicating that Ge can be used as a discriminate factor like Ti and V. Because of the availability of in situ analytical technique like laser ablation ICP‐MS, in situ Ge/Si ratio of magnetite can serve as a geochemical tracer and may provide new constraints on the genesis of banded iron formations.
Whole genome sequencing reveals a novel deletion variant in the KIT gene in horses with white spotted coat colour phenotypes
Authors: Dürig N. , Jude R. , Holl H. , Brooks S. A. , Lafayette C. , Jagannathan V. , Leeb T. 
Published: April 2017

SummaryWhite spotting phenotypes in horses can range in severity from the common white markings up to completely white horses. EDNRB, KIT, MITF, PAX3 and TRPM1 represent known candidate genes for such phenotypes in horses. For the present study, we re‐investigated a large horse family segregating a variable white spotting phenotype, for which conventional Sanger sequencing of the candidate genes’ individual exons had failed to reveal the causative variant. We obtained whole genome sequence data from an affected horse and specifically searched for structural variants in the known candidate genes. This analysis revealed a heterozygous ~1.9‐kb deletion spanning exons 10–13 of the KIT gene (chr3:77,740,239_77,742,136del1898insTATAT). In continuity with previously named equine KIT variants we propose to designate the newly identified deletion variant W22. We had access to 21 horses carrying the W22 allele. Four of them were compound heterozygous W20/W22 and had a completely white phenotype. Our data suggest that W22 represents a true null allele of the KIT gene, whereas the previously identified W20 leads to a partial loss of function. These findings will enable more precise genetic testing for depigmentation phenotypes in horses.
Antiretinal antibodies in central serous chorioretinopathy: prevalence and clinical implications
Authors: ten Berge Josianne C. E. M. , van Dijk Elon H. C. , Schreurs Marco W. J. , Vermeer Jacolien , Boon Camiel J. F. , Rothova Aniki 
Published: April 2017

AbstractPurposeTo investigate the possible role of autoimmune reactions directed against retinal tissue in central serous chorioretinopathy (CSC), by analysing the presence of serum antiretinal antibodies (ARAs) and establishing their clinical relevance.MethodsSixty‐three patients with CSC were included, and clinical characteristics were collected. Serum samples of all patients with CSC, 101 uveitis patients and 60 healthy donors were analysed for the presence of ARAs by indirect immunofluorescence. Furthermore, all CSC serum samples were analysed on Western blot. Correlations between laboratory findings and clinical features of CSC were determined by logistic regression.ResultsAntiretinal antibodies (ARAs) were present in 54% of the patients with CSC, in 46% of uveitis patients (p = 0.153) and in 17% of healthy controls (p < 0.001). The majority of ARAs in CSC were directed against photoreceptors (27%), which occurred significantly more often compared to uveitis patients (15%, p = 0.039) and to healthy controls (5%, p = 0.003). No associations between clinical CSC characteristics and the presence of ARAs were found.ConclusionSerum ARAs are present in more than half of the patients with CSC, and especially, ARAs directed against photoreceptors were detected more frequently compared to both healthy controls and uveitis patients. Further research is warranted to unravel the role of ARAs in the pathogenesis of CSC.
Prognostic impact of chromosomal aberrations and GNAQ, GNA11 and BAP1 mutations in uveal melanoma
Authors: Staby Kjersti M. , Gravdal Karsten , Mørk Sverre J. , Heegaard Steffen , Vintermyr Olav K. , Krohn Jørgen 
Published: April 2017

AbstractPurposeTo evaluate clinico‐pathological and molecular prognostic factors in a well‐defined series of posterior uveal melanoma (UM) with focus on chromosomal aberrations and mutations in the GNAQ, GNA11 and BRCA1‐associated protein 1 (BAP1) genes.MethodsFormalin‐fixed paraffin‐embedded (FFPE) tissue samples were obtained from 50 consecutive eyes enucleated for UM between 1993 and 2005. The material was tested for loss of chromosome 3 and gain of chromosome 8q gene signatures by selective molecular gene markers using multiplex ligation‐dependent probe amplification (MLPA), and for DNA mutations in the GNAQ, GNA11 and BAP1 genes.ResultsAfter a mean follow‐up of 83 months (range, 8–205 months), 21 patients had died of metastatic UM and 16 patients of other causes. Tumour diameter, ciliary body involvement, mixed/epithelioid cell types, mitotic index, Ki‐67 proliferation index, loss of chromosome 3 and gain of chromosome 8q showed statistically significant associations with metastatic disease. There were no significant differences in the prevalence of GNAQ and GNA11 mutations between patients with or without metastatic disease. Mutational analysis of the BAP1 gene was performed in 32 primary UM and in five UM liver metastases. Nine different BAP1 missense mutations were identified. BAP1 mutations were not more common in metastasizing than in nonmetastasizing UM.ConclusionThe molecular gene markers showing loss of chromosome 3 and gain of 8q gene signatures were associated with an increased risk of metastatic disease. BRCA1‐associated protein 1 (BAP1) gene mutation status had no prognostic significance. The frequency and spectrum of BAP1 mutations in UM may be more dependent on ethnicity and demographic variables than hitherto considered.
Prevalence and pathogen load of Campylobacter spp., Salmonella enterica and Escherichia coliO157/O145 serogroup in sheep faeces collected at sale yards and in abattoir effluent in Western Australia
Authors: Yang R , Abraham S , Gardner GE , Ryan U , Jacobson C 
Published: April 2017

ObjectiveDevelop a multiplex quantitative PCR assay to investigate the prevalence and shedding of Escherichia coli O157/O145, Salmonella spp. and Campylobacter spp. in sheep at sale yards and abattoirs.MethodsA qPCR for E. coli O157/O145 was developed, validated and multiplexed with an existing qPCR for Campylobacter and Salmonella enterica. The absolute numbers of E. coli O157/O145, Campylobacter and Salmonella in control samples was determined using droplet digital PCR. These were then used as the controls in the multiplex qPCR on a total of 474 sheep faecal samples collected from two saleyards over a 4‐month period (April–July 2014) and 96 effluent samples from an abattoir.ResultsThe mutiplex qPCR was specific with a sensitivity of 5 organisms/μL faecal DNA extract for Campylobacter, S. enterica and E. coli O157/O145. The overall prevalence of Campylobacter, S. enterica and E. coli O157/O145 in faecal samples was 5.7%, 3.6% and 8.4% and in effluent samples was 18.8%, 6.3% and 5.2%, respectively. The pathogen loads of Campylobacter, S. enterica and E. coli O157/O145 in faecal and effluent samples was also determined via mutiplex qPCR.ConclusionsThe overall prevalences of Campylobacter, S. enterica and E. coli O157/O145 were generally low (<6%), but point prevalences ranged considerably in healthy sheep (up to 26% for E. coli O157/O145). Further work to determine risk factors for shedding of bacterial organisms in meat sheep in the pre‐slaughter period (on‐farm, sale yards and lairage at abattoirs) could further reduce the risk of contamination of meat products.
E7 (1057ΔTA) mutation of the acidic α‐glucosidase gene causes Pompe's disease in Droughtmaster cattle
Authors: Lyons RE , Johnston DJ , McGowan MR , Laing A , Robinson B , Owen H , Hill BD , Burns BM 
Published: April 2017

ObjectiveTo determine whether known loss‐of‐function alleles of the acidic α‐glucosidase gene (GAA) are present in the Droughtmaster breed and, if so, whether the clinical signs and pathology of generalised glycogenosis (Pompe's disease) previously reported in other affected cattle are also seen in homozygous Droughtmasters.DesignExisting genomic and other diagnostic tests developed for generalised glycogenosis in cattle were used to test for the presence of the three known loss‐of‐function alleles of
GAA
in a herd of Droughtmaster cattle. Two calves with clinical signs of generalised glycogenosis were submitted for necropsy.ResultsOne loss‐of‐function
GAA
mutation (1057ΔTA or E7 allele) was identified using SNP chip technology and confirmed using conventional diagnostic DNA tests. Further testing demonstrated that the mutation was common within this herd and that two ill‐thrift calves were homozygous for the E7 allele. Parentage analysis confirmed both sire and dam as heterozygous carriers. Pathology consistent with generalised glycogenosis was found in the skeletal and cardiac muscle and spinal cord of both of the affected calves. The 1783C>T (E13) or 2454ΔCA (E18) mutations associated with generalised glycogenosis in the Brahman and Shorthorn breeds, respectively, were not detected.ConclusionThe lethal mutation 1057ΔTA of
GAA
is present in the Droughtmaster breed, with pathology identical to that reported in pure Brahman animals. Droughtmaster breeders should take action to prevent any increase in the prevalence of this lethal allele in the breed as it could cause both welfare issues and production losses if ignored.
Azilsartan Medoxomil, an Angiotensin II Receptor Antagonist for the Treatment of Hypertension
Authors: Hjermitslev Marie , Grimm Daniela G. , Wehland Markus , Simonsen Ulf , Krüger Marcus 
Published: April 2017

AbstractAzilsartan (AZL) medoxomil was approved by the United States Food and Drug Administration in 2011 for the treatment of hypertension and has shown promising results both in blood pressure (BP) reduction and in tolerability, but has not yet been taken into practice to the same extent as other angiotensin II receptor blockers (ARBs) that have been on the market for a longer period. AZL antagonizes the AT1 receptor for angiotensin II (ANG II), whereas angiotensin‐converting enzyme inhibitors block the conversion of angiotensin I to ANG II, but not alternative routes of formation of ANG II. The bioavailability of AZL is about 60% and it has a tmax of 1.5–3 hr and a half‐life of approximately 11 hr. With its IC50 of 7.4 nM after 5 hr of drug washout in radioligand assays, AZL has a tighter and longer‐lasting binding to the AT1 receptor by several orders of magnitude than other ARBs, which might lead to a more effective reduction in BP. Clinical studies have revealed that AZL doses of 40 and 80 mg/day reduce BP significantly better than maximal clinical doses of valsartan or olmesartan, while being well tolerated and exhibiting a spectrum of adverse effects comparable to those of other ARBs. These properties of AZL might lower the risk of cardiovascular disease and thereby reduce mortality rates. However, the existing mortality studies have not found this correlation, which should be further investigated.
Dual cyclin‐dependent kinase 4/6 inhibition by PD‐0332991 induces apoptosis and senescence in oesophageal squamous cell carcinoma cells
Authors: Chen Liang , Pan Jingxuan 
Published: April 2017

Background and PurposeAberrant activation of the cyclin D1‐cyclin‐dependent kinase 4/6 (CDK4/6)‐Rb signalling pathway is common in oesophageal squamous cell carcinoma (ESCC). PD‐0332991, a highly specific inhibitor of CDK4/6, has potent antitumour activity against many types of cancer. The purpose of this study was to examine the in vitro and in vivo antineoplastic effect of PD‐0332991 against the growth and metastasis of ESCC cells.Experimental ApproachCell viability and any synergy between PD‐0332991 and 5‐fluorouracil or cisplatin were measured by MTS assay and CalcuSyn software respectively. Cell migration and invasion were detected by wound healing and transwell assays. Apoptosis was evaluated by flow cytometry after staining annexin V‐FITC/PI. Cellular senescence was assessed by measuring SA‐β‐gal activity. Nude mouse xenograft models of ESCC were employed to determine the in vivo activity of PD‐0332991 against tumour growth and lung metastasis.Key ResultsPD‐0332991 inhibited cellular growth and induced mitochondrial‐dependent apoptosis in ESCC cells. PD‐0332991 also suppressed migration, invasion and the expression of MMP‐2 in ESCC cells. Furthermore, PD‐0332991 treatment caused cell senescence in a FOXM1‐dependent manner. In addition, there was synergy between PD‐0332991 and cisplatin or 5‐fluorouracil. Importantly, the xenografted tumour experiments demonstrated that PD‐0332991 potently inhibits ESCC cell growth and lung metastasis.Conclusions and ImplicationsPD‐0332991 can elicit a strong antitumour activity against ESCC growth and metastasis and may be a promising candidate drug for the treatment of patients with ESCC. Our results warrant a clinical trial to further evaluate the efficacy of PD‐0332991 in ESCC patients, even those with metastasis.
Factors influencing biased agonism in recombinant cells expressing the human α1A‐adrenoceptor
Authors: da Silva Junior Edilson Dantas , Sato Masaaki , Merlin Jon , Broxton Natalie , Hutchinson Dana S , Ventura Sabatino , Evans Bronwyn A , Summers Roger J 
Published: April 2017

Background and PurposeAgonists acting at GPCRs promote biased signalling via Gα or Gβγ subunits, GPCR kinases and β‐arrestins. Since the demonstration of biased agonism has implications for drug discovery, it is essential to consider confounding factors contributing to bias. We have examined bias at human α1A‐adrenoceptors stably expressed at low levels in CHO‐K1 cells, identifying off‐target effects at endogenous receptors that contribute to ERK1/2 phosphorylation in response to the agonist oxymetazoline.Experimental ApproachIntracellular Ca2+ mobilization was monitored in a Flexstation® using Fluo 4‐AM. The accumulation of cAMP and ERK1/2 phosphorylation were measured using AlphaScreen® proximity assays, and mRNA expression was measured by RT‐qPCR. Ligand bias was determined using the operational model of agonism.Key ResultsNoradrenaline, phenylephrine, methoxamine and A61603 increased Ca2+ mobilization, cAMP accumulation and ERK1/2 phosphorylation. However, oxymetazoline showed low efficacy for Ca+2 mobilization, no effect on cAMP generation and high efficacy for ERK1/2 phosphorylation. The apparent functional selectivity of oxymetazoline towards ERK1/2 was related to off‐target effects at 5‐HT1B receptors endogenously expressed in CHO‐K1 cells. Phenylephrine and methoxamine showed genuine bias towards ERK1/2 phosphorylation compared to Ca2+ and cAMP pathways, whereas A61603 displayed bias towards cAMP accumulation compared to ERK1/2 phosphorylation.Conclusion and ImplicationsWe have shown that while adrenergic agonists display bias at human α1A‐adrenoceptors, the marked bias of oxymetazoline for ERK1/2 phosphorylation originates from off‐target effects. Commonly used cell lines express a repertoire of endogenous GPCRs that may confound studies on biased agonism at recombinant receptors.