bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel mass spectrometry‐based method for determining insulin‐like growth factor 1: assessment in a cohort of subjects with newly diagnosed acromegaly
Authors: Kay Richard , Halsall David J. , Annamalai Anand K. , Kandasamy Narayanan , Taylor Kevin , Fenwick Susanna , Webb Alison , Wark Gwen , Pleasance Steve , Gurnell Mark 
Published: November 2012

SummaryObjectiveTo develop an alternative method to immunoassay for the quantitative analysis of insulin‐like growth factor 1 (IGF‐1) using a mass spectrometry (MS)‐based approach.Study design and patientsA stable isotope dilution Ultra High Performance Liquid Chromatography tandem MS (uHPLC‐MS/MS)‐based method for the quantification of IGF‐1 was developed. The method employed Selected Reaction Monitoring (SRM) of two tryptic peptides derived from IGF‐1, and utilised solid phase extraction for enrichment of the peptide fraction containing IGF‐1 rather than immunocapture, so was less susceptible to assay interference. Plasma samples from 25 consecutive unselected patients with newly diagnosed acromegaly, collected both before and after 24 weeks of primary medical therapy with Lanreotide Autogel®, were analysed by a widely used commercial immunoassay (Siemens Immulite 2000®) and by uHPLC‐MS/MS.ResultsThe uHPLC‐MS/MS method showed good correlation with the immunoassay over a wide range of IGF‐1 concentrations. The Passing and Bablock regression was: uHPLC‐MS/MS (nmol/l) = 1·37 (95% confidence interval: 1·26–1·46) × immunoassay (nmol/l) + 3·14 (95% confidence interval: –2·71 to 10·32). Six patients had discordant growth hormone (GH) and IGF‐1 levels following primary medical therapy, and in all six the immunoassay and uHPLC‐MS/MS platforms returned comparable results. The method was not affected by concentrations of IGFBP3 up to 12 500 ng/ml.ConclusionsuHPLC‐MS/MS offers an independent method for determining/validating IGF‐1 in subjects with acromegaly. Further studies, including the establishment of age‐ and sex‐matched reference ranges and calibration to the new International IGF‐1 standard IS 02/254, are now required to allow its introduction in to routine clinical use.
Role of sex steroids, intrahepatic fat and liver enzymes in the association between SHBG and metabolic features
Authors: Bonnet Fabrice , Velayoudom Cephise Fritz‐Line , Gautier Alain , Dubois Séverine , Massart Catherine , Camara Alioune , Larifla Laurent , Balkau Beverley , Ducluzeau Pierre‐Henri 
Published: November 2012

SummaryBackgroundSHBG and liver enzymes levels are both associated with the risk of type 2 diabetes. However, the relationship between SHBG with liver enzymes and intrahepatic fat content remain poorly understood.ObjectiveTo investigate whether SHBG is correlated with glucose and lipids levels and whether this association depends on fatty liver content, liver enzymes or sex hormone concentrations.Design and PatientsWe studied 233 dysmetabolic men with measures of plasma SHBG, total testosterone, 17β‐oestradiol, glucose, adiponectin, liver enzymes and hepatokines. Intrahepatic liver fat and visceral fat contents were measured by magnetic resonance imaging in 108 of these individuals.ResultsAfter adjustment for age, SHBG concentration was inversely correlated with fasting glucose (βstandardized = −0·21, P = 0·0007), HbA1c (βstandardized = −0·27, P < 0·0001), triglycerides (βstandardized = −0·19, P = 0·003) and positively correlated with HDL‐Cholesterol (βstandardized = 0·14, P = 0·03). These correlations persisted after adjustment for either total testosterone or 17β‐oestradiol levels. SHBG was not related to either fetuin A or FGF 21 concentrations. The inverse association of SHBG with HbA1c and glycaemia was not altered after adjusting for liver markers but was no longer significant after adjustment for hepatic fat content.ConclusionThe significant association between SHBG and fasting glycaemia, HbA1c and lipid levels in dysmetabolic men was not related to either sex hormones or markers of liver function, but was dependent on intrahepatic fat. This suggests that intrahepatic fat, but not alterations in liver function markers, may be involved in the association between SHBG and glucose and lipid metabolism.
A phylogenetic analysis of Sciomyzidae (Diptera) and some related genera
Authors: Tóthová Andrea , Rozkošný Rudolf , Knutson Lloyd , Kutty Sujatha Narayanan , Wiegmann Brian M. , Meier Rudolf 
Published: November 2012

AbstractSciomyzidae is a family of acalyptrate flies with 546 species in 61 genera that is among the most extensively studied groups of higher Diptera. Most of the known larvae are obligate enemies of Gastropoda. Hundreds of studies published over the past 50 years have resulted in detailed information concerning morphology of adults and immature stages, biology, development, behaviour, phenology and distribution. However, studies of phylogenetic relationships are based almost exclusively on morphological characters of adults, and no comprehensive molecular analysis across the family has been published. Here we fill this void by generating and analysing molecular data for 54 species of Sciomyzidae (22 genera), including Phaeomyiidae (one genus), and seven representative species of five other families of Sciomyzoidea (Coelopidae, Dryomyzidae, Helcomyzidae, Heteromyzidae and Huttoninidae) as outgroups. The reconstruction is based on morphological characters as well as nucleotide sequences for genes from the mitochondrial (12S, 16S, COI, COII, Cytb) and nuclear genome (28S, EF1α). The results are compared with recent morphological analyses. Our analyses support the monophyly of Sciomyzidae + Phaeomyiidae, and place Phaeomyiinae as a unique lineage within Sciomyzidae. A modified classification comprising three subfamilies is proposed. The major subfamily, Sciomyzinae, consists of two monophyletic and well separated groups, the tribes Sciomyzini and Tetanocerini.
One‐year Clinical Prediction in Chinese Ischemic Stroke Patients Using the CHADS2 and CHA2DS2‐VASc Scores: The China National Stroke Registry
Authors: Li Shu‐Ya , Zhao Xing‐Quan , Wang Chun‐Xue , Liu Li‐Ping , Liu Gai‐Fen , Wang Yi‐long , Wang Yong‐Jun 
Published: November 2012

SummaryAimsWe investigated whether CHADS2 or CHA2DS2‐VASc scores could be used to predict 1‐year prognosis in stroke recurrence, mortality, and mortality of ischemic stroke or transient ischemic attack (TIA) patients with nonvalvular atrial fibrillation (NVAF).MethodsPatients were selected from a national prospective registry in China. The clinical prediction of the scores was examined using the C statistic. Univariate and multivariate logistic regressions were performed to analyze the relevant risk factors.ResultsThousand two hundred and ninety‐seven of 22,216 patients were enrolled in the study. For stroke recurrence rate, the C statistic value was 0.53 (odds ratio [OR] 1.15, 95% confidence interval [CI]: 1.01 to 1.32) for CHADS2 and 0.55 (OR 1.14, 95% CI: 1.05 to 1.24) for CHA2DS2‐VASc; adding baseline National Institutes of Health Stroke Scale (NIHSS) score to these two scores, the value of C statistic was 0.58 (OR 1.25 95% CI: 1.14 to 1.37) and 0.58 (OR 1.19, 95% CI: 1.11 to 1.27), respectively.ConclusionsBoth CHADS2 and CHA2DS2‐VASc scores have limitations in predicting the 1‐year prognosis of stroke/TIA patients with NVAF in China. The predictive value of these two scores improved by adding the baseline NIHSS score.
Cold ischemic time is critical in outcomes of expanded criteria donor renal transplantation
Authors: Kim Suh Min , Ahn Sanghyun , Min Sang Il , Park Daedo , Park Taejin , Min Seung Kee , Kim Sang Joon , Ha Jongwon 
Published: November 2012

AbstractThe outcomes of expanded criteria donor (ECD) kidneys have been reported to be inferior compared with standard criteria donor (SCD) kidneys. However, the graft survival rate of ECD is not so inferior to SCD in Korea. The purposes of this study were to compare the outcomes of ECD kidneys with SCD kidneys and identify the influencing factors. We retrospectively studied 143 deceased donor transplants from August 2006 to June 2010. The patients were divided into SCD (n = 117) and ECD (n = 26) by UNOS criteria. The one‐ and three‐yr graft survival rates of SCD and ECD (99.1% and 94.4% vs. 100% and 92.9%, respectively, p = 0.15) were not significantly different between groups. The mean cold ischemic time (CIT) was 3.8 ± 2.2 h. When compared the outcome of ECD kidneys with data reported by Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients (OPTN/SRTR) (one‐ and three‐yr graft survival rate: 86.7% and 73.2%), the graft survival rate of our center was superior. In OPTN/SRTR data, transplant with CIT shorter than 11 h was only 20%. The outcomes of ECD grafts are outstanding and comparable with SCD grafts in our center, and the only distinguishing factor is markedly short CIT. Finishing the allocation before organ recovery and immediate operations after recovery could shorten the CIT.
Association of mycophenolic acid dose with efficacy and safety events in kidney transplant patients receiving tacrolimus: an analysis of the Mycophenolic acid Observational REnal transplant registry
Authors: Doria Cataldo , Greenstein Stuart , Narayanan Mohanram , Ueda Kimi , Wiland Anne , McCague Kevin , Sankari Bashir , Chan Laurence 
Published: November 2012

AbstractBackgroundDose‐finding studies for mycophenolic acid (MPA) in tacrolimus‐treated kidney transplant patients are lacking.MethodsData from 901de novokidney transplant recipients enrolled in the prospective, non‐interventional Mycophenolic acid Observational REnal (MORE) transplant registry were analyzed according to baseline dailyMPAdose (<2000, 2000 or >2000 mg).ResultsThe proportion of patients receiving 2000 and <2000 mg was 77.6% and 19.9% at baseline, 74.5% and 23.3% at month 1, 62.4% and 35.5% at month 3, 48.5% and 50.2% at month 6, and 44.1% and 55.2% at month 12. More patients were maintained on 2000 mg with enteric‐coated mycophenolate sodium (EC‐MPS) vs. mycophenolate mofetil (month 6, 52.7% vs. 43.0% [p = 0.02]; month 12, 47.3% vs. 39.4% [p = 0.08]). Multivariate modeling showed no significant effect of baselineMPAdose on 12‐month risk of biopsy‐proven acute rejection, graft loss or estimatedGFR, or on safety events includingMPAdiscontinuation other than a higher rate of gastrointestinal adverse events in patients with an initialMPAdose >2000 mg (p = 0.029) vs. 2000 mg.ConclusionsThese findings suggest that an initialMPAdose of <2000 mg does not compromise 12‐month efficacy in tacrolimus‐treated kidney transplants, but controlled trials are required and the lower threshold forMPAdose remains to be defined.
Alcohol and other drug use, club drug dependence and treatment seeking among lesbian, gay and bisexual young people in Sydney
Authors: Lea Toby , Reynolds Robert , de Wit John 
Published: November 2012

AbstractIntroduction and AimsSubstance use and substance use problems are often more prevalent in same‐sex attracted young people (SSAY), yet little to date has been published about substance use and problems in this population in Australia. This paper aimed to characterise patterns of alcohol use, club drug use and dependence, injecting drug use and engagement with treatment services, comparing lesbians, gay men, bisexual women and bisexual men.Design and MethodsA cross‐sectional, online survey was conducted with 572 SSAY in Sydney, aged 18 to 25 years. The Alcohol Use Disorders Identification Test—Consumption questions (AUDIT‐C) assessed hazardous alcohol use, and the Severity of Dependence Scale assessed club drug dependence.ResultsSeventy per cent of respondents had AUDIT‐C scores indicative of hazardous alcohol use, and 29% of respondents had used club drugs in the previous 6 months. Multivariate logistic regression showed that male respondents had a lower odds of hazardous alcohol use (adjusted odds ratio = 0.6, 95% confidence interval 0.4–0.9), but a higher odds of recent club drug use (adjusted odds ratio = 1.8, 95% confidence interval 1.2–2.7). Methamphetamine dependence was reported among half of respondents who reported use in the previous 6 months. Bisexual women were more likely than other respondents to have sought treatment for alcohol and other drug use, and overall treatment utilisation was low (6%).Discussion and ConclusionsThis study reports high rates of drinking and club drug use, and a possible underutilisation of alcohol and other drug treatment. The findings suggest that SSAY in Sydney may be at a high risk of alcohol‐ and drug‐related harm.
Brain magnetic resonance imaging and motor and intellectual functioning in 86 patients born at term with spastic diplegia
Authors: NUMATA YURIKA , ONUMA AKIRA , KOBAYASHI YASUKO , SATO‐SHIRAI IKUKO , TANAKA SOICHIRO , KOBAYASHI SATORU , WAKUSAWA KEISUKE , INUI TAKEHIKO , KURE SHIGEO , HAGINOYA KAZUHIRO 
Published: November 2012

Aim To investigate the association between magnetic resonance imaging (MRI) patterns and motor function, epileptic episodes, and IQ or developmental quotient in patients born at term with spastic diplegia.Method Eighty‐six patients born at term with cerebral palsy (CP) and spastic diplegia (54 males, 32 females; median age 20y, range 7–42y) among 829 patients with CP underwent brain MRI between 1990 and 2008. The MRI and clinical findings were analysed retrospectively. Intellectual disability was classified according to the Enjoji developmental test or the Wechsler Intelligence Scale for Children (3rd edition).Results The median ages at diagnosis of CP, assignment of Gross Motor Function Classification System (GMFCS) level, cognitive assessment, and MRI were 2 years (range 5mo–8y), 6 years (2y 8mo–19y), 6 years (1y 4mo–19y), and 7 years (10mo–30y) respectively. MRI included normal findings (41.9%), periventricular leukomalacia, hypomyelination, and porencephaly/periventricular venous infarction. The frequency of patients in GMFCS levels III to V and intellectual disability did not differ between those with normal and abnormal MRI findings. Patients with normal MRI findings had significantly fewer epileptic episodes than those with abnormal ones (p=0.001).Interpretation Varied MRI findings, as well as the presence of severe motor dysfunction and intellectual disability (despite normal MRI), suggest that patients born at term with spastic diplegia had heterogeneous and unidentified pathophysiology.
Expression of steroid 5α‐reductase isozymes in prostate of adult rats after environmental stress
Authors: Sánchez Pilar , Torres Jesús M. , Castro Beatriz , Olmo Asunción , del Moral Raimundo G. , Ortega Esperanza 
Published: November 2012

The elevated incidence of prostate cancer and benign prostatic hypertrophy is a cause of increasing public health concern in the Western world. The normal and pathological growth of the prostate are both dependent on stimulation by dihydrotestosterone, which is synthesized from circulating testosterone by two 5α‐reductase (5α‐R) isozymes, 5α‐reductase type 1 (5α‐R1) and 5α‐reductase type 2 (5α‐R2). Both isozymes have been implicated in prostate disease. We used quantitative RT‐PCR and immunohistochemistry, respectively, to quantify mRNA and protein levels of 5α‐R isozymes in the ventral prostate of adult rats under environmental stress conditions analogous to those found in some common workplace situations, i.e. artificial light, excessive heat, and the sensation of immobility in a small space. Transcription and expression levels of both 5α‐R isozymes were significantly higher in environmentally stressed rats than in unstressed rats. Increased 5α‐R isozyme levels may play a role in the development or maintenance of prostate disease. Further research is warranted to explore these effects of environmental stress on human health and their implications for environmental and occupational health policies.
Multiple catalytic activities of Escherichia coli lysyl‐tRNA synthetase (LysU) are dissected by site‐directed mutagenesis
Authors: Chen Xiaolong , Boonyalai Nonlawat , Lau Catherine , Thipayang Salinthip , Xu Yuhong , Wright Michael , Miller Andrew D. 
Published: November 2012

The heat‐inducible lysyl‐tRNA synthetase from Escherichia coli (LysU; EC6/1/1/6.html) converts ATP to diadenosine tri‐ and tetraphosphates (Ap3A/Ap4A) in the presence of l‐lysine/Mg2+/Zn2+. To understand LysU in more detail, 26 mutants were prepared: six of E264, four of R269 and sixteen mutants by alanine‐scanning of the inner shell/motif 2 loop. In the presence of glycerol and absence of exogenously added Zn2+/l‐lysine, we unexpectedly found that E264K catalysed the production of glycerol‐3‐phosphate, powered by ATP turnover to ADP. E264Q and E264N are also capable of this activity, but all three show little formation of Ap4A/Ap3A under normal conditions (additional Zn2+/l‐lysine/Mg2+). By contrast, wild‐type LysU has a weaker glycerol kinase‐like capability in the absence of Zn2+ and is dominated by Ap4A/Ap3A synthesis in its presence. Kinetic and isothermal titration calorimetry results suggest that E264 is a crucial residue for Zn2+ promotion of Ap4A/Ap3A synthesis. This is consistent with the hypothesis that E264 provides an anchor point for a Zn2+ ion complexed to the active site, with simultaneous coordination to the enzyme bound lysyl‐adenylate intermediate and secondary substrate ATP/ADP. The glycerol kinase‐like activity is uncovered on disruption of this specific coordination.
Molecular modeling of different substrate‐binding modes and their role in penicillin acylase catalysis
Authors: Novikov Fedor N. , Stroganov Oleg V. , Khaliullin Ilyas G. , Panin Nikolay V. , Shapovalova Irina V. , Chilov Ghermes G. , Švedas Vytas K. 
Published: November 2012

Molecular modeling was addressed to understand different substrate‐binding modes and clarify the role of two positively charged residues of the penicillin G acylase active site – βR263 and αR145 – in binding of negatively charged substrates. Although the electrostatic contribution to productive substrate binding was dominated by βR263 rather than αR145, it was found that productive binding was not the only possible mode of substrate placement in the active site. Two extra binding modes – nonproductive and preproductive – were located by means of molecular docking and dynamics with binding affinities comparable with the productive one. A unique feature of nonproductive and preproductive complexes was that the substrate's acyl group did not penetrate the hydrophobic pocket, but occupied a patch on the protein interface spanning from βR263 to αR145. Nonproductive and preproductive complexes competed with each other and productive binding mode, giving rise to increased apparent substrate binding. Preproductive complex revealed an ability to switch to a productive one during molecular dynamics simulations, and conformational plasticity of the penicillin G acylase active site was shown to be crucial for that. Nonproductive binding observed at molecular modeling corresponded well with experimentally observed substrate inhibition in penicillin acylase catalysis. By combining estimated free energies of substrate binding in each mode, and accounting for two possible conformations of the penicillin G acylase active site (closed and open) quantitative agreement with experimentally measured KM values was achieved. Calculated near‐attack conformation frequencies from corresponding molecular dynamics simulations were in a quantitative correlation with experimental kcat values and demonstrated adequate application of molecular modeling methods.
Effects of silver carp (Hypophthalmichthys molitrix) and nutrients on the plankton community of a deep, tropical reservoir: an enclosure experiment
Authors: ZHAO SHUAI‐YING , SUN YU‐PING , LIN QIU‐QI , HAN BO‐PING 
Published: November 2012

Summary1. An in situ enclosure experiment was conducted in a deep reservoir of southern China to examine (i) the effects of a low biomass (4 g wet weight m−3) of silver carp (Hypophthalmichthys molitrix) and nutrients on the plankton community and (ii) the response of Daphnia to eutrophication.2. In the absence of fish, Daphnia galeata dominated the zooplankton community, whereas calanoids were dominant in the fish treatments, followed by D. galeata. Silver carp stocking significantly reduced total zooplankton biomass, and that of D. galeata and Leptodorarichardi, but markedly increased the biomass of smaller cladocerans, copepod nauplii and rotifers. In contrast, nutrient enrichment had no significant effect on the plankton community except for cyclopoids.3. Chlorophyta, Cryptophyta and Bacillariophyta were dominant phytoplankton groups during the experiment. Chlorophyta with high growth rates (mainly Chlorella vulgaris in the fish enclosures and Ankyra sp. in the fishless enclosures) eventually dominated the phytoplankton community. Total phytoplankton biomass and the biomass of edible phytoplankton [greatest axial linear dimension (GALD) < 30 μm], Chlorophyta, Cryptophyta, Bacillariophyta and Cyanobacteria showed positive responses to fish stocking, while inedible phytoplankton (GALD ≥ 30 μm) was significantly reduced in the fish enclosures. However, there was no significant effect on the plankton community from the interaction of fish and nutrients.4. Overall, the impact of fish on the plankton community was much greater than that of nutrients. High total phosphorus concentrations in the control treatment and relatively low temperatures may reduce the importance of nutrient enrichment. These results suggest it is not appropriate to use a low biomass of silver carp to control phytoplankton biomass in warmer, eutrophic fresh waters containing large herbivorous cladocerans.
Tailored tobacco dependence support for mental health patients: a model for inpatient and community services
Authors: Parker Camilla , McNeill Ann , Ratschen Elena 
Published: November 2012

AbstractAimsAlthough smoking prevalence among people with severe mental illness is high, it remains largely unaddressed. This pragmatic pilot project aimed to develop and implement a tailored tobacco dependence service in mental health settings and to assess its impact, as well as barriers and facilitators to implementation.DesignAn integrative service model, spanning acute, rehabilitation and community services, including the design of tailored instruments and referral pathways, delivered by two mental health professionals.Setting and participantsFour adult acute and two rehabilitation wards (129 beds), and the community recovery team (2038 cases) of the United Kingdom's largest Mental Health Trust.MeasurementsAudit of smoking information in patient notes; service uptake; quit attempts; smoking cessation and reduction; qualitative data on implementation barriers/facilitators.FindingsA total of 110 patients attended at least one support session: 53 inpatients (23% of inpatient smokers) and 57 community (of unknown number of community smokers, as recording of smoking status is not mandatory). Thirty‐four of these (31%) made a quit attempt; 17 (15%) stopped smoking and 29 (26%) reduced cigarette consumption by up to 50% at the final contact. Barriers to service implementation related to: (i) trust policy, systems and procedures, (ii) staff knowledge and attitudes and (iii) illness‐related factors.ConclusionsDespite the strong anti‐smoking climate in the United Kingdom, including a law requiring smoke‐free policies in mental health settings, establishing a smoking cessation treatment service for people with mental illness proved difficult, due to complex systemic barriers. However, there is clearly a demand, by patients, for such a service.