bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structured endoscopic ultrasonography (EUS) training program improved knowledge and skills of trainees: Results from the Asian EUS Group
Authors: Wang Myrna Huixian , Dy Frederick , Vu Van Khien , Lim Lee Guan , Tayyab Ghias Un Nabi , Ratanachu‐ek Thawee , Samarasekera Dharmabandhu N , Dhir Vinay , Jin Zheng‐Dong , Kida Mitsuhiro , Seo Dong Wang , Wang Hsiu‐Po , Teoh Anthony , Hawes Robert , Varadarajulu Shyam , Yasuda Ken , Ho Khek Yu 
Published: February 2015

Background and AimA major reason impeding the growth of endoscopic ultrasound (EUS) in Asia is the lack of training availability. We aimed to prospectively evaluate the effectiveness of a short‐term structured EUS training program in improving the knowledge and skill of EUS among trainees.MethodsThe study was conducted in six workshops in six countries including Sri Lanka, Pakistan, Thailand, Vietnam, Singapore and Philippines, within a year. Trainees were evaluated using written and skill tests before and after completion of the training.ResultsPre‐ and post‐workshop written tests from a total of 62 trainees were analyzed. Compared with pre‐training, the trainees improved significantly in the overall mean (± SD) scores after the training (66.0 ± 0.3% to 77.5 ± 0.2%, P < 0.0001). Thirty‐one trainees were randomly selected to undergo a skill test before and after the course. Compared with pre‐training, the proportions of trainees who succeeded in locating each structure post‐training were: celiac axis (36–80.5%), pancreatic body (51.5–80.5%), pancreatic body and tail (42–77.5%), splenic vein and artery (48.5–84%), left kidney (60–83%), and spleen (47–83%). Overall, there was a significant improvement in the proportion of trainees’ successful localization of structures post‐training compared to before training (P < 0.0001).ConclusionFollowing a structured training program, trainees’ knowledge and skills in EUS improved significantly. Structured training courses appear to be an effective way of imparting EUS knowledge and skills to aspiring endosonographers in the Asian region.
Cardiovascular safety of the glucagon‐like peptide‐1 receptor agonist taspoglutide in people with type 2 diabetes: an individual participant data meta‐analysis of randomized controlled trials
Authors: Seshasai S. R. K. , Bennett R. L. , Petrie J. R. , Bengus M. , Ekman S. , Dixon M. , Herz M. , Buse J. B. , Ray K. K. 
Published: February 2015

AimsTo study the short‐term cardiovascular effects of the once‐weekly glucagon‐like peptide‐1 receptor agonist taspoglutide.MethodsWe conducted a meta‐analysis of individual‐participant data from nine randomized controlled trials in the T‐Emerge programme, which assessed the efficacy and safety of taspoglutide in type 2 diabetes. Our primary outcome was a composite of death from cardiovascular disease (CVD) and acute myocardial infarction, stroke and hospitalization for unstable angina.ResultsOverall, 7056 individuals were included in the analysis, and there were 67 primary endpoint events during 7478 person‐years of follow‐up (40 vs 27 events in the intervention vs control groups, respectively). The odds ratio for the composite endpoint among people randomized to taspoglutide was 0.94 (95% confidence interval 0.57–1.56), which was robust across multiple subgroups. Longer‐term data were not available as the development of taspoglutide was stopped because of gastrointestinal intolerance and serious hypersensitivity reactions.ConclusionsThe available data suggest that short‐term, once‐weekly administration of taspoglutide was not associated with an excess risk of CVD, and provide insights relevant to the development of other novel once‐weekly incretin mimetics.
Novel mutations in ATP1A3 associated with catastrophic early life epilepsy, episodic prolonged apnea, and postnatal microcephaly
Authors: Paciorkowski Alex R. , McDaniel Sharon S. , Jansen Laura A. , Tully Hannah , Tuttle Emily , Ghoneim Dalia H. , Tupal Srinivasan , Gunter Sonya A. , Vasta Valeria , Zhang Qing , Tran Thao , Liu Yi B. , Ozelius Laurie J. , Brashear Allison , Sweadner Kathleen J. , Dobyns William B. , Hahn Sihoun 
Published: February 2015

SummaryObjectiveMutations of ATP1A3 have been associated with rapid onset dystonia‐parkinsonism and more recently with alternating hemiplegia of childhood. Here we report one child with catastrophic early life epilepsy and shortened survival, and another with epilepsy, episodic prolonged apnea, postnatal microcephaly, and severe developmental disability. Novel heterozygous mutations (p.Gly358Val and p.Ile363Asn) were identified in ATP1A3 in these children.MethodsSubjects underwent next‐generation sequencing under a research protocol. Clinical data were collected retrospectively. The biochemical effects of the mutations on ATP1A3 protein function were investigated. Postmortem neuropathologic specimens from control and affected subjects were studied.ResultsThe mutations localized to the P domain of the Na,K‐ATPase α3 protein, and resulted in significant reduction of Na,K‐ATPase activity in vitro. We demonstrate in both control human brain tissue and that from the subject with the p.Gly358Val mutation that ATP1A3 immunofluorescence is prominently associated with interneurons in the cortex, which may provide some insight into the pathogenesis of the disease.SignificanceThe findings indicate these mutations cause severe phenotypes of ATP1A3‐related disorder spectrum that include catastrophic early life epilepsy, episodic apnea, and postnatal microcephaly.
Sertraline‐induced potentiation of the CYP3A4‐dependent neurotoxicity of carbamazepine: An in vitro study
Authors: Ghosh Chaitali , Hossain Mohammad , Spriggs Addison , Ghosh Arnab , Grant Gerald A. , Marchi Nicola , Perucca Emilio , Janigro Damir 
Published: February 2015

SummaryObjectiveDrug toxicity is a hurdle to drug development and to clinical translation of basic research. Antiepileptic drugs such as carbamazepine (CBZ) and selective serotonin reuptake inhibitors such as sertraline (SRT) are commonly co‐prescribed to patients with epilepsy and comorbid depression. Because SRT may interfere with cytochrome P450 (CYP) enzyme activity and CYPs have been implicated in the conversion of CBZ to reactive cytotoxic metabolites, we investigated in vitro models to determine whether SRT affects the neurotoxic potential of CBZ and the mechanisms involved.MethodsHuman fetal brain‐derived dopaminergic neurons, human brain microvascular endothelial cells (HBMECs), and embryonic kidney (HEK) cells were used to evaluate cytotoxicity of CBZ and SRT individually and in combination. Nitrite and glutathione (GSH) levels were measured with drug exposure. To validate the role of CYP3A4 in causing neurotoxicity, drug metabolism was compared to cell death in HEK CYP3A4 overexpressed and cells pretreated with the CYP3A4 inhibitor ketoconazole.ResultsIn all cellular systems tested, exposure to CBZ (127 μm) or SRT (5 μm) alone caused negligible cytotoxicity. By contrast CBZ, tested at a much lower concentration (17 μm) in combination with SRT (5 μm), produced prominent cytotoxicity within 15 min exposure. In neurons and HBMECs, cytotoxicity was associated with increased nitrite levels, suggesting involvement of free radicals as a pathogenetic mechanism. Pretreatment of HBMECs with reduced GSH or with the GSH precursor N‐acetyl‐l‐cysteine prevented cytotoxic response. In HEK cells, the cytotoxic response to the CBZ + SRT combination correlated with the rate of CBZ biotransformation and production of 2‐hydroxy CBZ, further suggesting a causative role of reactive metabolites. In the same system, cytotoxicity was potentiated by overexpression of CYP3A4, and prevented by CYP3A4 inhibitor.SignificanceThese results demonstrate an unexpected neurotoxic interaction between CBZ and SRT, apparently related to increased CYP3A4‐mediated production of reactive CBZ metabolites. The potential clinical implications of these findings are discussed.
The core‐independent promoter‐specific binding of Bacillus subtilis σB
Authors: Kuo Heng‐Hsu , Huang Wei‐Cheng , Lin Tzu‐Feng , Yeh Hsin‐Yi , Liou Kung‐Ming , Chang Ban‐Yang 
Published: February 2015

Bacillus subtilis σD is an alternative σ factor that possesses a core‐independent promoter −10 element binding specificity despite the lack of a distinct footprint on its cognate promoter. We wished to determine whether this property is common to alternative σ factors. To this end, we over‐expressed B. subtilis σB in Escherichia coli and analyzed its DNA binding ability by electrophoretic mobility shift assay and DNase I footprinting. The major complex formed by σB and its cognate promoter DNA is heparin‐sensitive. However, in contrast to the −10 element binding specificity observed for B. subtilis σD, the promoter binding of σB is specific for the −35 element. These and other results clearly demonstrate that alternative σ factors possess different promoter‐binding characteristics, and make core‐independent contributions to recognition of their cognate promoters.
Biocatalytic carboxylation of phenol derivatives: kinetics and thermodynamics of the biological Kolbe–Schmitt synthesis
Authors: Pesci Lorenzo , Glueck Silvia M. , Gurikov Pavel , Smirnova Irina , Faber Kurt , Liese Andreas 
Published: February 2015

Microbial decarboxylases, which catalyse the reversible regioselective ortho‐carboxylation of phenolic derivatives in anaerobic detoxification pathways, have been studied for their reverse carboxylation activities on electron‐rich aromatic substrates. Ortho‐hydroxybenzoic acids are important building blocks in the chemical and pharmaceutical industries and are currently produced via the Kolbe–Schmitt process, which requires elevated pressures and temperatures (≥ 5 bar, ≥ 100 °C) and often shows incomplete regioselectivities. In order to resolve bottlenecks in view of preparative‐scale applications, we studied the kinetic parameters for 2,6‐dihydroxybenzoic acid decarboxylase from Rhizobium sp. in the carboxylation‐ and decarboxylation‐direction using 1,2‐dihydroxybenzene (catechol) as starting material. The catalytic properties (Km, Vmax) are correlated with the overall thermodynamic equilibrium via the Haldane equation, according to a reversible random bi–uni mechanism. The model was subsequently verified by comparing experimental results with simulations. This study provides insights into the catalytic behaviour of a nonoxidative aromatic decarboxylase and reveals key limitations (e.g. substrate oxidation, CO2 pressure, enzyme deactivation, low turnover frequency) in view of the employment of this system as a ‘green’ alternative to the Kolbe–Schmitt processes.
Hypoalbuminemia, influenza vaccination and other factors related to the development of pneumonia acquired outside hospitals in southern Japan: A case–control study
Authors: Washio Masakazu , Kondo Kyoko , Fujisawa Nobumitsu , Harada Eiji , Tashiro Hideki , Mizokami Tetsuya , Nogami Hiroko , Iwanaga Tomoaki , Nakanishi Yoichi , Suzuki Kanzo , Ohfuji Satoko , Fukushima Wakaba , Hirota Yoshio ,   the Kyushu Task Force for CAP Risk in the Elderly
Published: February 2015

AimPneumonia is the third largest cause of death in Japan. Pneumonia continues to be one of the most common causes of morbidity, hospitalization and mortality, especially in the elderly. The aim of the present study was to evaluate the factors related to the development of pneumonia acquired outside hospitals among the Japanese elderly.MethodsWe carried out a hospital‐based, case–control study. Cases were patients who had been newly diagnosed with pneumonia acquired outside hospitals. For each case, one to three controls were defined as outpatients with other diseases (not pneumonia) at the same hospitals. All participants (i.e. 50 cases and 110 controls) were aged 65 years and older.ResultsCompared with control participants, hypoalbuminemia (<3.5 g/dL) and low body mass index (<18.0) were more common in pneumonia patients, whereas the proportion of those who could go out by themselves (i.e. self‐support in activities of daily living) and the vaccination rate of seasonal influenza were lower in patients with pneumonia than control participants. Even after controlling for age, sex, hospital and aforementioned four factors, hypoalbuminemia (OR 9.19, 95% CI 3.70–22.81) increased the risk of pneumonia, whereas seasonal influenza vaccination (OR 0.37, 95% CI 0.16–0.85) reduced the risk. Even after excluding those who lived in a nursing home, hypoalbuminemina (OR 12.19, 95% CI 4.29–34.63) increased the risk of pneumonia.ConclusionsHypoalbuminemia might be a risk factor for pneumonia among the elderly living in the community. Geriatr Gerontol Int 2016; 16: 223–229.
Impact of phosphomimetic and non‐phosphorylatable mutations of phospholemman on L‐type calcium channels gating in HEK 293T cells
Authors: Guo Kai , Wang Yue‐Peng , Zhou Zhi‐Wen , Jiang Yi‐Bo , Li Wei , Chen Xiao‐Meng , Li Yi‐Gang 
Published: February 2015

AbstractBackground: Phospholemman (PLM) is an important phosphorylation substrate for protein kinases A and C in the heart. Until now, the association between PLM phosphorylation status and L‐type calcium channels (LTCCs) gating has not been fully understood. We investigated the kinetics of LTCCs in HEK 293T cells expressing phosphomimetic or nonphosphorylatable PLM mutants. Methods: The LTCCs gating was measured in HEK 293T cells transfected with LTCC and wild‐type (WT) PLM, phosphomimetic or nonphosphorylatable PLM mutants: 6263AA, 6869AA, AAAA, 6263DD, 6869DD or DDDD. Results: WT PLM significantly slowed LTCCs activation and deactivation while enhanced voltage‐dependent inactivation (VDI). PLM mutants 6869DD and DDDD significantly increased the peak of the currents. 6263DD accelerated channel activation, while 6263AA slowed it more than WT PLM. 6869DD significantly enhanced PLM‐induced increase of VDI. AAAA slowed the channel activation more than 6263AA, and DDDD accelerated the channel VDI more than 6869DD. Conclusions: Our results demonstrate that phosphomimetic PLM could stimulate LTCCs and alter their dynamics, while PLM nonphosphorylatable mutant produced the opposite effects.
Sex‐linked inheritance, genetic correlations and sexual dimorphism in three melanin‐based colour traits in the barn owl
Authors: Roulin A. , Jensen H. 
Published: February 2015

AbstractTheory states that genes on the sex chromosomes have stronger effects on sexual dimorphism than genes on the autosomes. Although empirical data are not necessarily consistent with this theory, this situation may prevail because the relative role of sex‐linked and autosomally inherited genes on sexual dimorphism has rarely been evaluated. We estimated the quantitative genetics of three sexually dimorphic melanin‐based traits in the barn owl (Tyto alba), in which females are on average darker reddish pheomelanic and display more and larger black eumelanic feather spots than males. The plumage traits with higher sex‐linked inheritance showed lower heritability and genetic correlations, but contrary to prediction, these traits showed less pronounced sexual dimorphism. Strong offspring sexual dimorphism primarily resulted from daughters not expressing malelike melanin‐based traits and from sons expressing femalelike traits to similar degrees as their sisters. We conclude that in the barn owl, polymorphism at autosomal genes rather than at sex‐linked genes generate variation in sexual dimorphism in melanin‐based traits.
Referral of tuberculosis symptomatic clients from private pharmacies to public sector clinics for diagnosis and treatment in Cambodia
Authors: Bell Carolyn A. , Ilomäki Jenni , Pichenda Koeut , Duncan Gregory J. , Saini Bandana 
Published: February 2015

AbstractRationale, aims and objectivesCambodia is one of the 22 countries with a high burden of tuberculosis (TB). People often first seek treatment for cough and other TB symptoms through private pharmacies. The National Tuberculosis Programme trained willing private sector pharmacies to refer TB symptomatic clients to their closest public sector clinic for diagnosis and treatment. The study objective was to investigate factors associated with referral of TB symptomatic clients from pharmacies to public sector clinics in Phnom Penh, Cambodia.MethodFace‐to‐face structured interviews were conducted with staff from a stratified random sample of 180 private pharmacies in Phnom Penh in 2012. Trained interviewers were Khmer speakers. Logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs) for factors associated with self‐reported referral during the previous 3 months.ResultsFifty (29.6%) pharmacies reported that they had referred 125 clients (range 1–10) to public sector clinics during the previous 3 months. In total, 164 (96.5%) pharmacies reported that they always referred all TB symptomatic clients to DOTS (directly observed treatment, short course) clinics. More than 6‐year participation in the programme (OR 5.23, 95% CI 1.93–14.18) and willingness to always continue referring (OR 12.24, 95% CI 11.61–93.10) were associated with referral of one or more clients in the previous 3 months. Referral to the client's closest clinic was negatively associated with referral (OR 0.45, 95% CI 0.23–0.99).ConclusionPharmacies' ongoing commitment to the Referral Programme was strongly associated with referral. Increased advocacy among the high number of non‐referring pharmacies may improve programme performance. Factors negatively associated with referral may need investigation.
AThurstonian Model and Statistical Inference for the 2‐Alternative Choice Test with Both Test Pairs and Placebo Pairs
Authors: Bi Jian , Lee Hye‐Seong , O'Mahony Michael 
Published: February 2015

AbstractFor the paired difference or preference test applied to consumer research, the 2‐Alternative Choice (2‐AC) method that allows a “no difference” or “no preference” option is more suitable. For this method, using both test and placebo pairs is useful for estimating the degree of response bias among the consumers using the test and accurately estimating the degree of difference or preference between the test pairs. This paper proposes aThurstonian model for the 2‐ACfor both test pairs and placebo pairs in a test method. Maximum likelihood estimations are used for the parameters:d′, a perceived distance of difference or preference, and τ, a criterion and a decision parameter. Three methods are used for estimations of the covariance matrix for the parameter estimators: (1) using the built‐in functions in theS‐Plus andRpackages, which are based on maximum likelihood and observedFisher information; (2) the delta method, which is based on theTaylor series approximation; and (3) the bootstrap method, which is computer‐intensive with resampling. Statistical tests are discussed ford′and vectors of responses for test pairs and placebo pairs in both a monadic design and a paired design.R/S‐Plus codes are developed and provided for the calculations.Practical ApplicationsThis paper proposes aThurstonian model for the 2‐Alternative Choice (2‐AC) difference test or preference test method with both test pairs and placebo pairs. This test method provides more information than the 2‐ACmethod without an embedded placebo pair control. Applying this model, especially for the paired preference test method with a “no‐preference” option can be accurately and readily used for consumer research to achieve various business objectives such as reformulation and claim substantiation. UsingR/S‐Plus and built‐in functions and codes developed and provided in the paper, maximum likelihood estimation of parameters in the model, covariance matrix of the parameter estimators and statistical tests can be obtained and conducted easily and quickly.
Group B streptococcal disease and genotypes in Australian infants
Authors: Ko Danny WH , Zurynski Yvonne , Gilbert Gwendolyn L ,   GBS Study Group
Published: February 2015

AimsEstimate the incidence, risk factors and clinical features of group B streptococcal (GBS) disease in Australian infants and compare bacterial genotypes between infant disease and maternal carriage.MethodsThe Australian Paediatric Surveillance Unit conducted a study of invasive GBS disease in infants aged 0–90 days between July 2005 and June 2008. Clinical data were obtained by questionnaire. GBS isolates from affected infants and antenatal carriers were referred for genotyping.ResultsOne hundred fifty confirmed cases were reported: 88 early‐onset (EOD; 0–6 days) and 62 late‐onset disease (LOD). Based on review of selected laboratory records, they represented ∼1/3 of all cases. Estimated national EOD and LOD rates were 0.38 and 0.19/1000 live births, respectively. Admission to intensive care was common (44%), and 7% of infants died. One or more obstetric indications for intrapartum antibiotic prophylaxis (IAP) were identified in 51% of mothers; 53% of mothers were screened for GBS carriage, and screening was positive in 45%; only 25% of women with clinical or microbiological risk factors were given IAP (no significant differences between EOD and LOD groups). Distribution of GBS genotypes differed significantly between invasive and vaginal isolates: virulent serosubtype III‐2/sequence type 17 was strongly associated with LOD but uncommon among EOD and vaginal isolates.ConclusionsEstimated GBS disease rates remain relatively low despite poor predictive values of clinical and microbiological criteria for, and compliance with, IAP. Clinical and microbiological epidemiology of LOD differs significantly from that of EOD. Further reduction in infant morbidity and mortality from GBS disease will require new strategies.
Recombination Among Begomoviruses on Malvaceous Plants Leads to the Evolution of Okra Enation Leaf Curl Virus in Pakistan
Authors: Serfraz Saad , Amin Imran , Akhtar Khalid P. , Mansoor Shahid 
Published: February 2015

AbstractWhitefly transmitted begomoviruses (family Geminiviridae) are the major reason for significant yield losses of dicotyledonous crops in tropics and subtropics. Okra (Abelmoschus esculentus) is one of the important vegetable crops, and leaf curl disease caused by geminiviruses is the most important limiting factor for its production in Pakistan. Here, we report a new species of okra‐infecting begomovirus in south‐eastern region of Pakistan and the name Okra enation leaf curl virus (OELCuV) complex is proposed. This okra enation leaf curl disease complex (OELCuD) in Pakistan is found to be associated with Ageratum conyzoides symptomless alphasatellite (AConSLA). All efforts to clone the betasatellite were unsuccessful. Comprehensive sequence analyses suggest that intermalvaceous recombination between okra and cotton‐infecting begomoviruses resulted in the evolution of the new species. Surprisingly, Bhendi yellow vein mosaic virus (BYVMV) which has not been reported previously from Pakistan is the major parent while Cotton leaf curl Multan virus (CLCuMV) acts as a distant parent of the virus. Comparative recombination analysis also reveals that okra‐infecting begomoviruses from south and north‐western India is causing OELCuD in the Pakistan by recombining with CLCuMV at the Rep (1964–1513 nts). Recombination is common among geminiviruses and recombining of BYVMV and CLCuMV resulted in a new species: OELCuV. To the best of our knowledge, this evolution of a new species of okra‐infecting begomovirus is the first report of intermalvaceous recombination where Rep acts as the target region.