bluuebunny/crossref_metadata_2025_split huggingface dataset:
svclassify: a method to establish benchmark structural variant calls
Authors: Parikh Hemang , Mohiyuddin Marghoob , Lam Hugo Y. K. , Iyer Hariharan , Chen Desu , Pratt Mark , Bartha Gabor , Spies Noah , Losert Wolfgang , Zook Justin M. , Salit Marc 
Published: May 2015

AbstractBackground:The human genome contains variants ranging in size from small single nucleotide polymorphisms (SNPs) to large structural variants (SVs). High-quality benchmark small variant calls for the pilot National Institute of Standards and Technology (NIST) Reference Material (NA12878) have been developed by the Genome in a Bottle Consortium, but no similar high-quality benchmark SV calls exist for this genome. Since SV callers output highly discordant results, we developed methods to combine multiple forms of evidence from multiple sequencing technologies to classify candidate SVs into likely true or false positives. Our method (svclassify) calculates annotations from one or more aligned bam files from many high-throughput sequencing technologies, and then builds a one-class model using these annotations to classify candidate SVs as likely true or false positives.Results:We first used pedigree analysis to develop a set of high-confidence breakpoint-resolved large deletions. We then used svclassify to cluster and classify these deletions as well as a set of high-confidence deletions from the 1000 Genomes Project and a set of breakpoint-resolved complex insertions from Spiral Genetics. We find that likely SVs cluster separately from likely non-SVs based on our annotations, and that the SVs cluster into different types of deletions. We then developed a supervised one-class classification method that uses a training set of random non-SV regions to determine whether candidate SVs have abnormal annotations different from most of the genome. To test this classification method, we use our pedigree-based breakpoint-resolved SVs, SVs validated by the 1000 Genomes Project, and assembly-based breakpoint-resolved insertions, along with semi-automated visualization using svviz.Conclusions:We find that candidate SVs with high scores from multiple technologies have high concordance with PCR validation and an orthogonal consensus method MetaSV (99.7% concordant), and candidate SVs with low scores are questionable. We distribute a set of 2676 high-confidence deletions and 68 high-confidence insertions with high svclassify scores from these call sets for benchmarking SV callers. We expect these methods to be particularly useful for establishing high-confidence SV calls for benchmark samples that have been characterized by multiple technologies.
Character trees from transcriptome data: origin and individuation of morphological characters and the so-called “species signal”
Authors: Musser Jacob M. , Wagner Günter P. 
Published: May 2015

AbstractWe elaborate a framework for investigating the evolutionary history of morphological characters. We argue that morphological character trees generated by phylogenetic analysis of transcriptomes provide a useful tool for identifying causal gene expression differences underlying the development and evolution of morphological characters. They also enable rigorous testing of different models of morphological character evolution and origination, including the hypothesis that characters originate via divergence of repeated ancestral characters. Finally, morphological character trees provide evidence that character transcriptomes undergo concerted evolution. We argue that concerted evolution of transcriptomes can explain the so-called “species-specific clustering” found in several recent comparative transcriptome studies. The species signal is the phenomenon that transcriptomes cluster by species rather than character type, even though the characters are older than the respective species. We suggest that concerted gene expression evolution results from mutations that alter gene regulatory network interactions shared by the characters under comparison. Thus, character trees generated from transcriptomes allow us to investigate the variational independence, or individuation, of morphological characters at the level of genetic programs.
Stochastic models of evidence accumulation in changing environments
Authors: Veliz-Cuba Alan , Kilpatrick Zachary P. , Josić Krešimir 
Published: May 2015

ABSTRACTOrganisms and ecological groups accumulate evidence to make decisions. Classic experiments and theoretical studies have explored this process when the correct choice is fixed during each trial. However, the natural world constantly changes. Using sequential analysis we derive a tractable model of evidence accumulation when the correct option changes in time. Our analysis shows that ideal observers discount prior evidence at a rate determined by the volatility of the environment, and that the dynamics of evidence accumulation is governed by the information gained over an average environmental epoch. A plausible neural implementation of an optimal observer in a changing environment shows that, in contrast to previous models, neural populations representing alternate choices are coupled through excitation.
miR-551a and miR-551b-3p target GLIPR2 and promote tumor growth in High-Risk Head and Neck Cancer by modulating autophagy
Authors: Karanam Narasimha Kumar , Ding Liang-Hao , Hwang Tae Hyun , Tang Hao , Story Michael D. 
Published: May 2015

AbstractDistant metastasis (DM) and local-regional recurrence (LR) after radiation and chemo therapy are major cause of treatment failure for patients with head and neck squamous cell carcinoma. However, detailed underlying mechanisms leading to DM and LR in patients are not fully understood yet. MiRNA have been proposed as biomarkers in a variety of biological and medical conditions such as cancer and stress response. The advantages of miRNA as a biomarker lies in its stability in tissues as well as body fluids, hence the potential for non-invasive diagnosis and prognosis. In this study, towards understanding the molecular mechanism causing DM and LR in HN cancer patients we performed miRNA expression profiling using tumor samples from 118 head and neck cancer patients treated by post-operative radiotherapy (PORT) at M.D. Anderson Cancer Center from 1992 to 1999. All patients were considered to be at high-risk for recurrence having histologically proven advanced squamous cell carcinoma. Amongst these samples, 41 found to have distant metastasis (DM), 53 responded without relapse (no evidence of disease (NED)) to PORT. Comparison of miRNA expression between DM and NED specimens using two-way ANOVA identified 28 miRNAs that were differentially expressed with statistical significance (FDR < 0.2 and fold change > 1.5). Amongst these 28 miRNAs seen in the DM and NED outcome groups, miRNAs 551a and 551b are significantly associated with the DM group. Interestingly these two miRNAs share same seed sequence. Moreover Kaplan-Meir survival analysis in our data set and two other data sets suggested that miR-551a and miR-551b expressions are associated with poor survival in patients. We further performed cell proliferation, migration and invasion assays using the HN5 and UMSCC-17B head and neck cancer cell lines by transfection of either mimic or an inhibitor of miR-551a and miR-551b. The results suggested that miR-551a and miR-551b mimics promote proliferation, migration and invasion whereas the inhibitor decreased. Further studies indicated that these miRNAs target GLIPR2 expression and miR-551a, miR-551b and GLIPR2 axis at least in part plays an important role in tumor progression. Hence we need to further explore miR-551a and miR-551b-3p role in HN cancer progression in detail in in-vivo models to use them as therapeutic targets in future.
Document delivery demand and service review at the University of Kent
Authors: Werner Matthias 
Published: May 2015

Purpose
– This paper aims to investigate the document delivery demand at the University of Kent and describes the recent changes to the document delivery service and their impact.

Design/methodology/approach
– Statistical data from 2007 to 2015 and user feedback have been examined.

Findings
– There is a combination of reasons behind the high level of demand for interlibrary loan (ILL) material at the University of Kent, most notably the specific needs of users and library policy regarding document delivery.

Originality/value
– A study of one of the very few UK universities to experience an increase in ILL in the past few years.
The emasculation of frogs
Authors: Hirsch Peter Buell 
Published: May 2015

Purpose
– This article aims to suggest some ways in which the effectiveness of critical scientific communication might be improved. The persistence of anti-vaccine rhetoric, disputes about climate change and other scientific controversies have shone a light on the difficulty of communicating scientific information effectively to the public.

Design/methodology/approach
– The article looks at some recent research into neuroscience and human decision-making to suggest some best practices in communicating about science to the public.

Findings
– This literature review suggests that if we can embed rational arguments into a rich emotional narrative, we are more likely to overcome public skepticism and suspicion.

Originality/value
– While there has been much focus on human decision-making and cognitive bias, the relevant research has not often been related to the effectiveness of scientific communication.
Tracheal intubation in patients with anticipated difficult airway using Boedeker intubation forceps and McGrath videolaryngoscope
Authors: Strøm C. , Barnung S. , Kristensen M. S. , Bøttger M. , Tvede M. F. , Rasmussen L. S. 
Published: May 2015

BackgroundVideolaryngoscopes with sharp angulated blades improve the view of the vocal cords but this does not necessarily result in higher success rates of intubation The aim of this study was to evaluate the efficacy of using Boedeker intubation forceps in conjunction with McGrath Series 5 Videolaryngoscope (MVL) in patients with predictors for difficult intubation.MethodsThe study was conducted at the Department of Anaesthesia, Copenhagen University Hospital from September to December 2013. Patients with one or more predictors of difficult intubation scheduled for general anaesthesia were assessed for eligibility. Patients were intubated using Boedeker intubation forceps and MVL. The primary endpoint was time to intubation. The secondary endpoints were intubation success rate, number of intubation attempts, intubation conditions and post‐operative hoarseness.ResultsThirty‐three patients were assessed for eligibility, and 25 patients were included in the study with a median SARI score of 3 (IQR 3–4). Twenty‐two (88%, 95% confidence interval [74–100%]) of the patients were successfully intubated by the method with a median time to intubation of 115 s (IQR 78–247). Steering and advancement of the tube were reported as acceptable in 21 (84%) and 22 cases (88%), respectively, and excellent in 10 cases (45%) for both measures. Ten cases (40%) were intubated on the first attempt. There were three cases (12%) of failed intubation; in these cases, successful intubation was obtained by using a styletted tube.Conclusion(s)Most patients with anticipated difficult intubation can be successfully intubated with Boedeker intubation forceps and MVL. However, endotracheal tube placement failed in 3/25 patients despite a good laryngeal view.
A guideline for the use of variable rate intravenous insulin infusion in medical inpatients
Authors: George S. , Dale J. , Stanisstreet D. ,   the Joint British Diabetes Societies (JBDS) for Inpatient Care,   the JBDS Medical VRIII Writing Group
Published: May 2015

AbstractThe present paper summarizes the key recommendations in a recent publication produced by the Joint British Diabetes Societies for Inpatient Care on the use of variable rate i.v. insulin infusion in ‘medical’ inpatients. The full guideline is available at http://www.diabetologists-abcd.org.uk/JBDS/JBDS_IP_VRIII.pdf and is designed to be a practical guide that can used by any healthcare professional who manages medical inpatients with hyperglycaemia. Its main aim is to allow variable rate i.v. insulin infusion to be used safely, effectively and efficiently for this specific group of inpatients.
Early specialist care for diabetes: who benefits most? A propensity score‐matched cohort study
Authors: Booth G. L. , Shah B. R. , Austin P. C. , Hux J. E. , Luo J. , Lok C. E. 
Published: May 2015

AbstractAimsTo examine whether early endocrinologist care reduces the risk of cardiovascular complications among newly diagnosed patients with diabetes of differing complexity.MethodsWe conducted a population‐based propensity score‐matched cohort study using provincial health data from Ontario, Canada. Adults (≥ 30 years) diagnosed with diabetes between 1 April 1998 and 31 March 2006 who received endocrinologist care in the first year of diagnosis were matched to a comparison group receiving primary care alone (N = 79 020) based on propensity scores and medical complexity (assigned using information on chronic conditions). Individuals were followed for 3‐ and 5‐year outcomes, including non‐fatal acute myocardial infarction or coronary heart disease death (primary endpoint), major cardiovascular events (acute myocardial infarction, stroke) or all‐cause death, amputation and end‐stage renal disease.ResultsAmong medically complex patients, early endocrinologist care was associated with a lower 3‐year incidence of the primary endpoint (hazard ratio 0.89, 95% CI 0.78–1.01) and major cardiovascular events or all‐cause death (hazard ratio 0.91, 95% CI 0.85–0.97). These effects persisted after accounting for a higher incidence of end‐stage renal disease on follow‐up and were greatest in those with ≥ 3 visits to an endocrinologist (primary endpoint: hazard ratio 0.69, 95% CI 0.56–0.86 and 0.61, 95% CI 0.45–0.82, for unadjusted and end‐stage renal disease adjusted analyses, respectively). In contrast, no benefit was observed in the non‐medically complex subgroup. Overall effects were similar at 5 years.ConclusionsEarly endocrinologist care is associated with a lower incidence of cardiovascular events and death among newly diagnosed patients with diabetes who have comorbid medical conditions.
Twice‐ rather than once‐daily basal insulin is associated with better glycaemic control in Type 1 diabetes mellitus 12 months after skills‐based structured education in insulin self‐management
Authors: Hopkinson H. E. , Jacques R. M. , Gardner K. J. , Amiel S. A. , Mansell P. 
Published: May 2015

AbstractAimThis study investigates the relationship between basal insulin regimen and glycaemic outcomes 12 months after skills‐based structured education in the UK Dose Adjustment for Normal Eating (DAFNE) programme for Type 1 diabetes mellitus.MethodRetrospective analysis of data from 892 DAFNE participants from 11 UK centres.ResultsMean HbA1c 12 months after DAFNE was lower in those using twice‐ rather than once‐daily basal insulin after correcting for differences in baseline HbA1c, age and duration of diabetes; difference –2 (95% CI –3 to –1) mmol/mol [–0.2 (–0.3 to –0.1)%], P = 0.009. The greatest fall in HbA1c of –5 (–7 to –3) mmol/mol [–0.4 (–0.6 to –0.3)%], P < 0.001 occurred in those with less good baseline control, HbA1c ≥ 58 mmol/mol, who switched from once‐ to twice‐daily basal insulin. There was no difference in the 12‐month HbA1c between users of glargine, detemir and NPH insulin after correcting for other variables. Relative risk of severe hypoglycaemia fell by 76% and ketoacidosis by 63% 12 months after DAFNE. The rate of severe hypoglycaemia fell from 0.82 to 0.23 events/patient year in twice‐daily basal insulin users. In the group with greatest fall in HbA1c, the estimated relative risk for severe hypoglycaemia in twice‐daily basal insulin users versus once daily at 12 months was 1.72 (0.88–3.36, P = 0.110).ConclusionAfter structured education in adults with Type 1 diabetes mellitus, use of basal insulin twice rather than once daily was associated with lower HbA1c, independent of insulin type, with significant reductions in severe hypoglycaemia and ketoacidosis in all groups.
Electrical penetration graphs indicate that tricin is a key secondary metabolite of rice, inhibiting phloem feeding of brown planthopper, Nilaparvata lugens
Authors: Zhang Zhenfei , Cui Baiyuan , Zhang Yang 
Published: May 2015

AbstractTricin (5,7,4′‐trihydroxy‐3′,5′‐dimethoxyflavone) is a valuable secondary metabolite which is widely present in gramineous plants, including cultivated rice (Oryza sativa L.) (Poaceae). It can defend the rice plant against damage by the brown planthopper (BPH), Nilaparvata lugens (Stål) (Hemiptera: Delphacidae), one of the most important pests of rice. This study was conducted to elucidate the mechanisms of action of tricin on BPH feeding behavior. BPH feeding behavior in resistant (Rathu Heenati, RHT) and susceptible (Taichuang native 1, TN1) rice varieties and artificial diets was monitored using the electrical penetration graph (EPG) technique. Tricin concentrations in leaves of varieties RHT and TN1 were quantitatively analyzed by liquid chromatography, coupled to tandem mass spectrometric techniques. Six (NP and N1‐5) and four (NP, N1, N2, and N4) types of waveforms occurred during feeding on rice plants and artificial diets, respectively. The tricin concentration of rice varieties was correlated with total and average durations of N4. Moreover, EPG data indicated that tricin significantly increased the duration of non‐probing and pathway periods and strongly inhibited phloem ingestion (N4). The inhibition was strongly dose dependent, resulting in complete suppression of activity in the phloem region when the tricin concentration was increased to 1 g l−1. This study revealed that tricin disturbed the feeding behavior of BPH mainly by increasing the non‐probe period and inhibiting phloem ingestion. We confirmed the hypothesis that tricin is a ‘stylet probing stimulant’ of rice planthoppers as proposed in previous studies. The information on the ecological effect of tricin from this study may be useful to clarify the resistance mechanism against BPH of RHT and other tricin‐containing rice varieties.
Bioequivalence of oral and intravenous carbamazepine formulations in adult patients with epilepsy
Authors: Tolbert Dwain , Cloyd James , Biton Victor , Bekersky Ihor , Walzer Mark , Wesche David , Drummond Rebecca , Lee Deborah 
Published: May 2015

SummaryObjectiveTo evaluate the safety, tolerability, and comparative pharmacokinetics (PK) of intravenous and oral carbamazepine.MethodsIn this phase 1, open‐label study, adult patients with epilepsy on a stable oral carbamazepine dosage (400–2,000 mg/day) were converted to intravenous carbamazepine (administered at 70% of the oral dosage). A 28‐day outpatient period preceded an up to 10‐day inpatient period and a 30‐day follow‐up period. Intravenous carbamazepine was administered over 15 or 30 min every 6 h on days 1–7; some patients in the 15‐min group were eligible to receive four 2‐ to 5‐min (rapid) infusions on day 8. Patients underwent blood sampling to determine the area under the concentration–time curve (AUC) for carbamazepine and metabolite carbamazepine‐10,11‐epoxide following oral (day 0) and intravenous carbamazepine administration (days 1, 7, and 8). Bioequivalence was evaluated in patients with normal renal function (creatinine clearance >80 ml/min). Safety assessments were conducted through day 38.ResultsNinety‐eight patients enrolled and 77 completed the PK component. The mean daily oral and intravenous carbamazepine dosage for 64 PK‐evaluable patients with normal renal function was 962.5 and 675.1 mg (70% of oral dosage), respectively. Steady‐state minimum concentration (Cmin) and overall exposure (AUC0–24) for intravenous carbamazepine infused over 30, 15, or 2–5 min were similar to oral carbamazepine. The 90% confidence intervals (CIs) for the ratios of the adjusted means for AUC0–24, maximum concentration (Cmax), and Cmin were within the 80%–125% bioequivalence range for 30‐min intravenous infusions versus oral administration, but exceeded the upper limit for Cmax for the 15‐min and rapid infusions. All intravenous carbamazepine infusions were well tolerated.SignificanceIntravenous carbamazepine infusions (70% of oral daily dose) of 30‐, 15‐, and 2‐ to 5‐min duration, given every 6 h, maintained patients’ plasma carbamazepine concentrations. Intravenous carbamazepine 30‐min infusions were bioequivalent to oral carbamazepine in patients with normal renal function; rapid infusions were well‐tolerated in this study.
Ecosystem‐scale volatile organic compound fluxes during an extreme drought in a broadleaf temperate forest of the Missouri Ozarks (central USA)
Authors: Seco Roger , Karl Thomas , Guenther Alex , Hosman Kevin P. , Pallardy Stephen G. , Gu Lianhong , Geron Chris , Harley Peter , Kim Saewung 
Published: May 2015

AbstractConsiderable amounts and varieties of biogenic volatile organic compounds (BVOCs) are exchanged between vegetation and the surrounding air. These BVOCs play key ecological and atmospheric roles that must be adequately represented for accurately modeling the coupled biosphere–atmosphere–climate earth system. One key uncertainty in existing models is the response of BVOC fluxes to an important global change process: drought. We describe the diurnal and seasonal variation in isoprene, monoterpene, and methanol fluxes from a temperate forest ecosystem before, during, and after an extreme 2012 drought event in the Ozark region of the central USA. BVOC fluxes were dominated by isoprene, which attained high emission rates of up to 35.4 mg m−2 h−1 at midday. Methanol fluxes were characterized by net deposition in the morning, changing to a net emission flux through the rest of the daylight hours. Net flux of CO2 reached its seasonal maximum approximately a month earlier than isoprenoid fluxes, which highlights the differential response of photosynthesis and isoprenoid emissions to progressing drought conditions. Nevertheless, both processes were strongly suppressed under extreme drought, although isoprene fluxes remained relatively high compared to reported fluxes from other ecosystems. Methanol exchange was less affected by drought throughout the season, confirming the complex processes driving biogenic methanol fluxes. The fraction of daytime (7–17 h) assimilated carbon released back to the atmosphere combining the three BVOCs measured was 2% of gross primary productivity (GPP) and 4.9% of net ecosystem exchange (NEE) on average for our whole measurement campaign, while exceeding 5% of GPP and 10% of NEE just before the strongest drought phase. The meganv2.1 model correctly predicted diurnal variations in fluxes driven mainly by light and temperature, although further research is needed to address model BVOC fluxes during drought events.