bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atypical Antipsychotic Exposure May Not Differentiate Metabolic Phenotypes of Patients with Schizophrenia
Authors: Ward Kristen M. , Yeoman Larisa , McHugh Cora , Kraal A. Zarina , Flowers Stephanie A. , Rothberg Amy E. , Karnovsky Alla , Das Arun K. , Ellingrod Vicki L. , Stringer Kathleen A. 
Published: May 2018

Study ObjectivePatients with schizophrenia are known to have higher rates of metabolic disease than the general population. Contributing factors likely include lifestyle and atypical antipsychotic (AAP) use, but the underlying mechanisms are unknown. The objective of this study was to identify metabolomic variability in adult patients with schizophrenia who were taking AAPs and grouped by fasting insulin concentration, our surrogate marker for metabolic risk.DesignMetabolomics analysisParticipantsNinety‐four adult patients with schizophrenia who were taking an AAP for at least 6 months, with no changes in their antipsychotic regimen for the previous 8 weeks, and who did not require treatment with insulin, participated in the study. Twenty age‐ and sex‐matched nonobese (10 subjects) and obese (10 subjects) controls without cardiovascular disease or mental health diagnoses were used to match the body mass index (BMI) range of the patients with schizophrenia to account for metabolite concentration differences attributable to BMI.Measurements and Main ResultsExisting serum samples were used to identify aqueous metabolites (to differentiate fasting insulin concentration quartiles) and fatty acids with quantitative nuclear magnetic resonance and gas chromatography methods, respectively. To exclude metabolites from our pathway mapping analysis that were due to variability in weight, we also subjected serum samples from the nonobese and obese controls to the same analyses. Patients with schizophrenia had a median age of 47.0 years (interquartile range 41.0–52.0 years). Using a false discovery rate threshold of less than 25%, 10 metabolites, not attributable to weight, differentiated insulin concentration quartiles in patients with schizophrenia and identified variability in one‐carbon metabolism between groups. Patients with higher fasting insulin concentrations (quartiles 3 and 4) also trended toward higher levels of saturated fatty acids compared with patients with lower fasting insulin concentrations (quartiles 1 and 2).ConclusionOur results illustrate the utility of metabolomics to identify pathways underlying variable fasting insulin concentration in patients with schizophrenia. Importantly, no significant difference in AAP exposure was observed among groups, suggesting that current antipsychotic use may not be a primary factor that differentiates middle‐aged adult patients with schizophrenia by fasting insulin concentration.
Variation in Cardiovascular Risk Related to Individual Antimuscarinic Drugs Used to Treat Overactive Bladder: A UK Cohort Study
Authors: Arana Alejandro , Margulis Andrea V. , McQuay Lisa J. , Ziemiecki Ryan , Bartsch Jennifer L. , Rothman Kenneth J. , Franks Billy , D'Silva Milbhor , Appenteng Kwame , Varas‐Lorenzo Cristina , Perez‐Gutthann Susana 
Published: May 2018

BackgroundBlocking muscarinic receptors could have an effect on cardiac function, especially among elderly patients with overactive bladder (OAB).Study ObjectiveTo investigate the risk of cardiovascular (CV) events in users of antimuscarinic drugs to treat OAB.Design, Setting, and ParticipantsCohort study of new users of darifenacin, fesoterodine, oxybutynin, solifenacin, tolterodine, or trospium, 18 years or older, in the United Kingdom's Clinical Practice Research Datalink (CPRD), 2004–2012.Outcome Measurements and Main ResultsUsing tolterodine as the reference, we estimated propensity‐score–stratified incidence rate ratios (IRRs) for acute myocardial infarction, stroke, CV mortality, major adverse cardiac events (MACE, a combined end point of the previous three), and all‐cause death for individual antimuscarinic drugs. The study cohort included 119,912 new users of OAB drugs. The mean age at cohort entry was 62 years, 70% were female, and the mean follow‐up was 3.3 years. The adjusted IRR for MACE and current use of oxybutynin compared with current use of tolterodine was 1.14 (95% confidence interval [CI] 1.01–1.30). In contrast, the IRR was 0.65 (CI 0.56–0.76) for current use of solifenacin compared with tolterodine. In this study, performed with health care data, the distribution of risk factors was relatively similar across users of different OAB drugs and, although our analyses controlled for a range of measured potential confounders, residual confounding cannot be ruled out.ConclusionsIn an observational comparative study of users of medications to treat OAB conducted in routine clinical practice, the risk for CV side effects was increased in users of oxybutynin and decreased in users of solifenacin compared with users of tolterodine.
Investigating the effect of school‐wide positive behavioral interventions and supports on student learning and behavioral problems in elementary and middle schools
Authors: Ryoo Ji Hoon , Hong Saahoon , Bart William M. , Shin Jaehyun , Bradshaw Catherine P. 
Published: May 2018

AbstractMany states have scaled up School‐Wide Positive Behavioral Interventions and Supports (SW‐PBIS) with the goal of improving student behavior and academic outcomes. Although the effects of SW‐PBIS on behavioral and discipline outcomes have been promising, the findings for academic achievement have been inconclusive and are often limited to cross‐sectional data. This paper examined the longitudinal effect of SW‐PBIS on student behavioral problems and academic achievement growth in elementary and middle schools using propensity score matching. We found no statistically significant longitudinal effects of SW‐PBIS on either student behavior problems or academic achievement among elementary and middle schools in this quasi‐experimental design, even though the positive direction of longitudinal changes would be identified. The result raised questions about the efficacy of SW‐PBIS using a statewide achievement test when scaled up to a state level. Additional research is needed to better understand the impact of SW‐PBIS using rigorous scale‐up designs.
Enhancing executive function skills in preschoolers through a mindfulness‐based intervention: A randomized, controlled pilot study
Authors: Wood Laura , Roach Andrew T. , Kearney Moriah A. , Zabek Faith 
Published: May 2018

AbstractExecutive functions (EFs) develop rapidly in preschoolers and lay an important foundation for school readiness. One potential method of supporting EF development is through mindfulness‐based interventions (MBIs). Whereas studies with older children and adults have supported this approach, research with young children has been more limited. In the current study, we evaluated the effectiveness, acceptability, and feasibility of Mini‐Mind, a 12‐session MBI created specifically for preschoolers. We used a randomized controlled design in a sample of 27 (intervention n = 12) preschoolers (3–5 years old). The evaluation included indirect measures of EF skills completed by teachers who were blinded to the experimental condition of the students. Additionally, parents, teachers, children, and facilitators provided feedback about the acceptability and feasibility of the intervention. Findings revealed mostly nonsignificant, small‐to‐medium effects in favor of the intervention group on indirect measures of EF skills. Furthermore, Mini‐Mind was rated as highly feasible and acceptable by children and stakeholders. Overall, the findings support the implementation and continued evaluation of Mini‐Mind in more diverse settings.
Multiple target site resistance to glyphosate in junglerice (Echinochloa colona) lines from California orchards
Authors: Morran Sarah , Moretti Marcelo L , Brunharo Caio A , Fischer Albert J , Hanson Bradley D 
Published: May 2018

ABSTRACTBACKGROUNDIn California specialty cropping systems such as vineyards and orchards, Echinochloa colona is present as a summer annual weed. It is able to germinate throughout the growing season whenever favorable conditions are present, and management relies heavily on glyphosate applications. Glyphosate‐resistant (GR) E. colona biotypes are present in the state, but the levels of resistance observed suggest that there may be differences in mechanisms of resistance among populations.RESULTSEchinochloa colona lines collected from different regions of California's Central Valley presented resistance levels ranging from 1.4 to 4.3‐fold compared to susceptible lines. No differences in the absorption and translocation of [14C]‐glyphosate were observed among lines. Resistant lines accumulated eight‐fold less shikimic acid after treatment with 435 and 870 g a.e. ha−1 glyphosate compared to the most susceptible line. Sequencing of a region of the EPSPS gene revealed three single nucleotide changes leading to amino acid substitutions at Proline 106, including Pro106Leu, Pro106Thr and Pro106Ser.CONCLUSIONThese results indicate that an altered target site in EPSPS is contributing to resistance in these lines and resistance has evolved independently, multiple times in the Central Valley of California. Additional research is needed to further understand the genomic contributions of resistance loci in this polyploid weed species. © 2018 Society of Chemical Industry
Liquid chromatography/electrospray ionization tandem mass spectrometry study of repaglinide and its forced degradation products
Authors: Purna Chander C. , Raju B. , Ramesh M. , Shankar G. , Srinivas R. 
Published: May 2018

RationaleStress stability studies of drugs have been recognized as an essential part of the drug development process. These studies are used to investigate the intrinsic stability of the drugs and for the development of a selective stability indicating assay method (SIAM). Stress testing is also useful for the formulation and packaging development, shelf‐life determination and designing of manufacturing processes. As per regulatory guidelines, stress degradation studies and structural characterization should be carried out to establish degradation pathways of the drug, which is essential from both the efficacy and safety point of view. As the stress stability studies of repaglinide have not been reported in the literature, the present study has been undertaken.MethodsRepaglinide (RP), an oral anti‐diabetic drug, was subjected to hydrolysis (acidic, alkaline and neutral), oxidation, photolysis and thermal stress conditions as per International Conference on Harmonization (ICH) guidelines Q1A (R2). The chromatographic separation of the drug and its degradation products (DPs) was achieved on an Agilent XDB C‐18 column using the gradient elution method with a mobile phase consisting of 20 mM ammonium acetate and acetonitrile at flow rate of 1.0 mL min−1. The DPs were characterized using liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI‐MS/MS) in combination with accurate mass measurements.ResultsThe drug degraded under hydrolytic and oxidative stress, while it was stable under thermal and photolytic stress conditions. In total, six DPs were formed and the LC/MS method described here can resolve all DPs from the parent as well as from each other under various stress conditions. To elucidate the structures of DPs, fragmentation of the [M + H]+ ions of RP and its DPs was studied by using LC/ESI‐MS/MS combined with accurate mass measurements.ConclusionsThe forced degradation of RP carried out as per ICH guidelines results in the formation of six degradation products which have been characterized using LC/MS/MS in combination with accurate mass measurements.
A new retrospective, multi‐evidence veterinary drug screening method using drift tube ion mobility mass spectrometry
Authors: Xu Zhenzhen , Li Jianzhong , Chen Ailiang , Ma Xin , Yang Shuming 
Published: May 2018

RationaleThe retrospectivity (the ability to retrospect to a previously unknown compound in raw data) is very meaningful for food safety and risk assessment when facing new emerging drugs. Accurate mass and retention time based screening may lead to false positive and false negative results so a new retrospective, reliable platform is desirable.MethodsDifferent concentration levels of standards with and without matrix were analyzed using ion mobility (IM)‐quadrupole‐time‐of‐flight (QTOF) mass spectrometry to collect retrospective accurate mass, retention time, drift time and tandem mass spectrometry (MS/MS) evidence for identification in a single experiment. The isomer separation ability of IM and the four‐dimensional (4D) feature abundance quantification abilities were evaluated for veterinary drugs for the first time.ResultsThe sensitivity of the IM‐QTOF workflow was obviously higher than that of the traditional database searching algorithm [find by formula (FbF) function] for QTOF. In addition, the IM‐QTOF workflow contained most of the results from FbF and removed the false positive results. Some isomers were separated by IM and the 4D feature abundance quantitation removed interferences with similar accurate masses and showed good linearity.ConclusionsA new retrospective, multi‐evidence platform was built for veterinary drug screening in a single experiment. The sensitivity was significantly improved and the data can be used for quantification. The platform showed its potential to be used for food safety and risk assessment.
Mechanical Polyprotein Assembly Using Sfp and Sortase‐Mediated Domain Oligomerization for Single‐Molecule Studies
Authors: Liu Haipei , Ta Duy Tien , Nash Michael A. 
Published: May 2018

AbstractSingle‐molecule force spectroscopy (SMFS) with the atomic force microscope (AFM) provides remarkable details on the energy landscapes governing protein (un)folding and intermolecular complex dissociation. In such experiments, multidomain polyproteins consisting of multiple copies of independently foldable domains provide internal controls identifiable by characteristic contour length increments, unfolding forces, and/or unfolding substeps. Here, a new approach to polyprotein synthesis is presented relying on posttranslational enzyme‐mediated oligomerization of domains. Mutant variants of immunoglobulin 27 (I27) and a bacterial cellulose binding module (CBM) fused to an Ig‐like X‐module (XMod), and a mechanostable receptor called Dockerin (Doc) are produced with complementary peptide tags. By utilizing 4′‐phosphopantetheinyl transferase and Sortase A, the system enables I27‐domain oligomerization into polyproteins of varying lengths followed by C‐terminal capping with mechanostable Doc. The number of oligomerized domains per molecule, the unfolding forces, and the complex rupture forces of posttranslationally assembled polyproteins are characterized using >40 h automated AFM–SMFS with a Cohesin (Coh)‐modified cantilever. Use of the Coh–Doc interaction to unfold polyproteins provides a high yield of ≈ 3800 specific single‐molecule interaction curves. This approach is advantageous for assembly of polyproteins from domains that lack proper folding or are insoluble in a polyprotein format.
Opinions about STEM content and classroom experiences as predictors of upper secondary school students' career aspirations to become researchers or teachers
Authors: Šorgo Andrej , Dojer Brina , Golob Nikolaja , Repnik Robert , Repolusk Samo , Pesek Igor , Ploj Virtič Mateja , Špernjak Andreja , Špur Natalija 
Published: April 2018

AbstractThe shortage of qualified STEM teachers and researchers in these fields can be recognized as an existing and forthcoming problem. The aim of the present study was to explore the influence of the content of STEM subjects Biology, Chemistry, Informatics, Mathematics, Physics, and Technics and Technology and corresponding classroom experiences, as perceived by students, in elementary and general secondary schools on student's career aspirations and ambition to work as researchers or educators as their career choice. The sample comprised 552 upper general school students (ages 17 to 19) in their last two years before entering University. We hypothesized that a combination of general interest in each of the six listed disciplines, together with the content taught in elementary and upper secondary school, together with respective classroom experiences, will influence career aspirations expressed by ranking their wish to work as educators or researchers. With the use of Structural Equation Modeling, we revealed that Biology, Chemistry, and Physics can statistically significantly explain career aspirations to become a researcher. However, Informatics, Mathematics, and Technics and Technology cannot. None of the listed disciplines positively predicts career aspirations to become an educator. From the correlation between ranked aspirations toward a research and an educational career (r = –.03; p = .964), we can conclude that most of those who considered a career as a researcher as a plausible option do not share the same opinion about a career in education.
Prediction of adverse pregnancy outcome in monochorionic diamniotic twin pregnancy complicated by selective fetal growth restriction
Authors: Monaghan C. , Kalafat E. , Binder J. , Thilaganathan B. , Khalil A. 
Published: April 2018

ABSTRACTObjectiveTo identify key factors associated with adverse perinatal outcome in monochorionic diamniotic twin pregnancy complicated by selective fetal growth restriction (sFGR).MethodsThis was a retrospective cohort study of all monochorionic diamniotic twin pregnancies diagnosed with sFGR at ≥ 16 weeks' gestation, in a single tertiary referral center between March 2000 and May 2015. The presence of coexisting twin–twin transfusion syndrome (TTTS) was noted. Fetal biometry and Doppler indices, including those of the umbilical artery (UA) and ductus venosus (DV), were recorded at the time of diagnosis. The type of sFGR was diagnosed according to the pattern of end‐diastolic flow in the UA of the smaller twin. DV pulsatility indices for veins (DV‐PIV) were converted to Z‐scores and estimated fetal weight values to centiles, to correct for gestational age (GA). Cox proportional hazards model was used to examine for independent predictors of adverse perinatal outcome, which was defined according to survival and included both intrauterine fetal demise and neonatal death of the FGR twin.ResultsWe analyzed 104 pregnancies, of which 66 (63.5%) were diagnosed with Type‐I and 38 (36.5%) with Type‐II sFGR at initial presentation. In pregnancies complicated by Type‐II sFGR, the diagnosis of sFGR was made earlier than in those complicated by Type‐I sFGR (mediam GA, 19.6 vs 21.5 weeks; P = 0.012), and Type‐II sFGR was associated with increased risk of adverse perinatal outcome (intrauterine demise of the smaller twin, 34.2% vs 10.6%; P = 0.004). Twin pregnancies complicated by sFGR resulting in perinatal demise had a significantly earlier diagnosis (P = 0.002) and lower birth‐weight centile of the smaller twin (P < 0.01), those with Type‐I sFGR had earlier GA at delivery (P = 0.007) and those with Type‐II sFGR had higher DV‐PIV Z‐score of the smaller twin (P = 0.003), when compared with pregnancies resulting in live birth. Coexisting TTTS had no significant impact on the perinatal outcome of pregnancies diagnosed with either Type‐I or Type‐II sFGR (P > 0.05 for both). Earlier GA at diagnosis (hazard ratio (HR), 0.70 (95% CI, 0.56–0.88); P = 0.002), Type‐II sFGR (HR, 3.53 (95% CI, 1.37–9.07); P = 0.008) and higher DV‐PIV Z‐score (HR, 1.36 (95% CI, 1.12–1.65); P = 0.001) were significantly associated with increased risk of adverse perinatal outcome of the smaller twin.ConclusionsPregnancies complicated by Type‐II sFGR are diagnosed significantly earlier and are associated with increased risk of adverse perinatal outcome compared with those with Type‐I sFGR. Coexisting TTTS has no significant impact on the perinatal outcome of pregnancies diagnosed with either Type‐I or Type‐II sFGR. Earlier GA at diagnosis, Type‐II sFGR and higher DV‐PIV Z‐score are associated significantly with increased risk of adverse perinatal outcome of the smaller twin. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
Cuckoo search for wind farm optimization with auxiliary infrastructure
Authors: Afanasyeva Svetlana , Saari Jussi , Pyrhönen Olli , Partanen Jarmo 
Published: May 2018

AbstractThis paper focuses on the optimization problem of a wind farm layout. This area of research is currently receiving widespread attention, as optimal positioning of the turbines promotes the financial viability of the wind farm and enhances the competitiveness of wind projects in the energy market. In this work, cuckoo search (CS), a modern population‐based metaheuristic optimization algorithm, is used. The objective is to find the turbine layout and types that maximize the net present value of the wind farm, while constraints on the turbine positions have to be met. The following constraints are considered: Firstly, the minimum distance between turbines for safe operation; secondly, a realistic wind farm shape including forbidden zones for installation and the existing infrastructure. Furthermore, the optimization of the wind farm includes an algorithm to find the least expensive layout of the wind farm roads and the electrical collector system. The algorithm is based on Dijkstra's shortest path and Prim's minimum spanning tree algorithms. The test results indicate that the infrastructure cost has a significant effect on the optimum wind farm solution. A genetic algorithm, commonly applied to wind farm micro‐siting problems, is used to benchmark the performance of the CS. The results show that the CS is capable of consistently finding better solutions than the genetic algorithm.
LARP1 on TOP of ribosome production
Authors: Fonseca Bruno D. , Lahr Roni M. , Damgaard Christian K. , Alain Tommy , Berman Andrea J. 
Published: May 2018

The ribosome is an essential unit of all living organisms that commands protein synthesis, ultimately fuelling cell growth (accumulation of cell mass) and cell proliferation (increase in cell number). The eukaryotic ribosome consists of 4 ribosomal RNAs (rRNAs) and 80 ribosomal proteins (RPs). Despite its fundamental role in every living organism, our present understanding of how higher eukaryotes produce the various ribosome components is incomplete. Uncovering the mechanisms utilized by human cells to generate functional ribosomes will likely have far‐reaching implications in human disease. Recent biochemical and structural studies revealed La‐related protein 1 (LARP1) as a key new player in RP production. LARP1 is an RNA‐binding protein that belongs to the LARP superfamily; it controls the translation and stability of the mRNAs that encode RPs and translation factors, which are characterized by a 5′ terminal oligopyrimidine (5′TOP) motif and are thus known as TOP mRNAs. The activity of LARP1 is regulated by the mammalian target of rapamycin complex 1 (mTORC1): a eukaryotic protein kinase complex that integrates nutrient sensing with mRNA translation, particularly that of TOP mRNAs. In this review, we provide an overview of the role of LARP1 in the control of ribosome production in multicellular eukaryotes.This article is categorized under:

Translation > Translation Regulation
RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications
RNA Processing > Capping and 5′ End Modifications