bluuebunny/crossref_metadata_2025_split huggingface dataset:
aBayesQR: A Bayesian method for reconstruction of viral populations characterized by low diversity
Authors: Ahn Soyeon , Vikalo Haris 
Published: January 2017

AbstractRNA viruses replicate with high mutation rates, creating closely related viral populations. The heterogeneous virus populations, referred to as viral quasispecies, rapidly adapt to environmental changes thus adversely affecting efficiency of antiviral drugs and vaccines. Therefore, studying the underlying genetic heterogeneity of viral populations plays a significant role in the development of effective therapeutic treatments. Recent high-throughput sequencing technologies have provided invaluable opportunity for uncovering the structure of quasispecies populations (i.e., reconstruction of viral sequences and discovery of their relative frequencies). However, accurate reconstruction of viral quasispecies remains difficult due to limited read-lengths and presence of sequencing errors. The problem is particularly challenging when the strains in a population are highly similar, i.e., the sequences are characterized by low mutual genetic distances, and further exacerbated if some of those strains are relatively rare; this is the setting where state-of-the-art methods struggle. In this paper, we present a novel viral quasispecies reconstruction algorithm, aBayesQR, that employs a maximum-likelihood framework to infer individual sequences in a mixture from high-throughput sequencing data. The search for the most likely quasispecies is conducted on long contigs that our method constructs from the set of short reads via agglomerative hierarchical clustering; operating on contigs rather than short reads enables identification of close strains in a population and provides computational tractability of the Bayesian method. Results on both simulated and real HIV-1 data demonstrate that the proposed algorithm generally outperforms state-of-the-art methods; aBayesQR particularly stands out when reconstructing a set of closely related viral strains (e.g., quasispecies characterized by low diversity).
A miRNA catalogue and ncRNA annotation of the short-living fishNothobranchius furzeri
Authors: Baumgart Mario , Barth Emanuel , Savino Aurora , Groth Marco , Koch Philipp , Petzold Andreas , Arisi Ivan , Platzer Matthias , Marz Manja , Cellerino Alessandro 
Published: January 2017

ABSTRACTBackground:The short-lived fishNothobranchius furzeriis the shortest-lived vertebrate that can be cultured in captivity and was recently established as a model organism for aging research. Small non-coding RNAs, especially miRNAs, are implicated in age-dependent control of gene expression.Results:Here, we present a comprehensive catalogue of miRNAs and several other non-coding RNA classes (ncRNAs) forNothobranchius furzeri. Analyzing multiple small RNA-Seq libraries, we show most of these identified miRNAs are expressed in at least one of sevenNothobranchiusspecies. Additionally, duplication and clustering ofN. furzerimiRNAs was analyzed and compared to the four fish speciesDanio rerio,Oryzias latipes,Gasterosteus aculeatusandTakifugu rubripes. A peculiar characteristic ofN. furzerias compared to other teleosts was a duplication of the miR-29 cluster.Conclusion:The completeness of the catalogue we provide is comparable to that of zebrafish. This catalogue represents a basis to investigate the role of miRNAs in aging and development in this species.Availability:All supplementary material can be found online athttp://www.rna.uni-jena.de/en/supplements/nothobranchius-furzeri-mirnome/.
A Fast Approximate Algorithm for Mapping Long Reads to Large Reference Databases
Authors: Jain Chirag , Dilthey Alexander , Koren Sergey , Aluru Srinivas , Phillippy Adam M. 
Published: January 2017

AbstractEmerging single-molecule sequencing technologies from Pacific Biosciences and Oxford Nanopore have revived interest in long read mapping algorithms. Alignment-based seed-and-extend methods demonstrate good accuracy, but face limited scalability, while faster alignment-free methods typically trade decreased precision for efficiency. In this paper, we combine a fast approximate read mapping algorithm based on minimizers with a novel MinHash identity estimation technique to achieve both scalability and precision. In contrast to prior methods, we develop a mathematical framework that defines the types of mapping targets we uncover, establish probabilistic estimates of p-value and sensitivity, and demonstrate tolerance for alignment error rates up to 20%. With this framework, our algorithm automatically adapts to different minimum length and identity requirements and provides both positional and identity estimates for each mapping reported. For mapping human PacBio reads to the hg38 reference, our method is 290x faster than BWA-MEM with a lower memory footprint and recall rate of 96%. We further demonstrate the scalability of our method by mapping noisy PacBio reads (each ≥ 5 kbp in length) to the complete NCBI RefSeq database containing 838 Gbp of sequence and > 60, 000 genomes.
Dealing with false‐positive and false‐negative errors about species occurrence at multiple levels
Authors: Guillera‐Arroita Gurutzeta , Lahoz‐Monfort José Joaquín , van Rooyen Anthony R. , Weeks Andrew R. , Tingley Reid 
Published: January 2017

Summary

Accurate knowledge of species occurrence is fundamental to a wide variety of ecological, evolutionary and conservation applications. Assessing the presence or absence of species at sites is often complicated by imperfect detection, with different mechanisms potentially contributing to false‐negative and/or false‐positive errors at different sampling stages. Ambiguities in the data mean that estimation of relevant parameters might be confounded unless additional information is available to resolve those uncertainties.

Here, we consider the analysis of species detection data with false‐positive and false‐negative errors at multiple levels. We develop and examine a two‐stage occupancy‐detection model for this purpose. We use profile likelihoods for identifiability analysis and estimation, and study the types of additional data required for reliable estimation. We test the model with simulated data, and then analyse data from environmental DNA (eDNA) surveys of four Australian frog species. In our case study, we consider that false positives may arise due to contamination at the water sample and quantitative PCR‐sample levels, whereas false negatives may arise due to eDNA not being captured in a field sample, or due to the sensitivity of laboratory tests. We augment our eDNA survey data with data from aural surveys and laboratory calibration experiments.

We demonstrate that the two‐stage model with false‐positive and false‐negative errors is not identifiable if only survey data prone to false positives are available. At least two sources of extra information are required for reliable estimation (e.g. records from a survey method with unambiguous detections, and a calibration experiment). Alternatively, identifiability can be achieved by setting plausible bounds on false detection rates as prior information in a Bayesian setting. The results of our case study matched our simulations with respect to data requirements, and revealed false‐positive rates greater than zero for all species.

We provide statistical modelling tools to account for uncertainties in species occurrence survey data when false negatives and false positives could occur at multiple sampling stages. Such data are often needed to support management and policy decisions. Dealing with these uncertainties is relevant for traditional survey methods, but also for promising new techniques, such as eDNA sampling.
Insufficient evidence for ‘shaken baby syndrome’ – a systematic review
Authors: Lynøe Niels , Elinder Göran , Hallberg Boubou , Rosén Måns , Sundgren Pia , Eriksson Anders 
Published: January 2017

AbstractShaken baby syndrome has typically been associated with findings of subdural haematoma, retinal haemorrhages and encephalopathy, which are referred to as the triad. During the last decade, however, the certainty with which the triad can indicate that an infant has been violently shaken has been increasingly questioned. The aim of this study was to determine the diagnostic accuracy of the triad in detecting that an infant had been shaken. The literature search was performed using PubMed, Embase and the Cochrane Library up to October 15, 2015. Relevant publications were assessed for the risk of bias using the QUADAS tool and were classified as having a low, moderate or high risk of bias according to predefined criteria. The reference standards were confessions or witnessed cases of shaking or accidents. The search generated 3773 abstracts, 1064 were assessed as possibly relevant and read as full texts, and 30 studies were ultimately included. Of these, 28 were assessed as having a high risk of bias, which was associated with methodological shortcomings as well as circular reasoning when classifying shaken baby cases and controls. The two studies with a moderate risk of bias used confessions and convictions when classifying shaken baby cases, but their different designs made a meta‐analysis impossible. None of the studies had a low risk of bias.Conclusion: The systematic review indicates that there is insufficient scientific evidence on which to assess the diagnostic accuracy of the triad in identifying traumatic shaking (very low‐quality evidence). It was also demonstrated that there is limited scientific evidence that the triad and therefore its components can be associated with traumatic shaking (low‐quality evidence).
Retrospective study shows that doxapram therapy avoided the need for endotracheal intubation in most premature neonates
Authors: Flint Robert , Halbmeijer Nienke , Meesters Naomi , van Rosmalen Joost , Reiss Irwin , van Dijk Monique , Simons Sinno 
Published: January 2017

AbstractAimUsing doxapram to treat neonates with apnoea of prematurity might avoid the need for endotracheal intubation and invasive ventilation. We studied whether doxapram prevented the need for intubation and identified the predictors of the success.MethodsThis was a retrospective study of preterm infants born from January 2006 to August 2014 who received oral or intravenous doxapram. Success was defined as no need for endotracheal intubation, due to apnoea, during doxapram therapy. Univariable and multivariable logistic regression analyses identified predictors of success during the first 48 hours of doxapram therapy.ResultsData on 203 patients with a median gestational age of 26.1 (interquartile range 25.1–27.4) weeks were analysed. During the first 48 hours of doxapram therapy, 157 (77%) patients did not need endotracheal intubation and 127 (63%) patients were successfully treated over the entire treatment course. The median postnatal age at the start of doxapram therapy was 20 days (interquartile range 12–30). Postnatal age and a lower fraction of inspired oxygen at the start of doxapram therapy were significant predictors of success (odds ratio 0.964, 95% confidence interval 0.938–0.991, p = 0.001).ConclusionOral and intravenous doxapram effectively treated most cases of apnoea in preterm infants, avoiding the need for intubation.
Evaluation of single and multiple doses of a novel mGlu2 agonist, a potential antipsychotic therapy, in healthy subjects
Authors: McColm Juliet , Brittain Claire , Suriyapperuma Subha , Swanson Steven , Tauscher‐Wisniewski Sitra , Foster Joanne , Soon Danny , Jackson Kimberley 
Published: February 2017

AimsThe safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of single and multiple doses of a novel mGlu2 agonist were assessed in healthy males.MethodsIn two, Phase 1 investigator‐ and subject‐blind, placebo‐controlled studies, oral doses of prodrug LY2979165 were evaluated: single doses (20–150 mg, N = 30) and multiple once‐daily (QD) doses (20–400 mg; N = 84), using a titration regimen. The plasma and urine PK of LY2979165 and active moiety, 2812223, were measured. Cerebrospinal fluid (CSF) was collected to determine PK and neurotransmitter levels. Safety parameters were assessed throughout.ResultsNausea and vomiting were dose limiting following single doses; dose titration allowed higher doses to be tested over 14 days. The most common adverse events related to LY2979165 were dizziness, vomiting, nausea, somnolence and headache. The plasma PK of 2812223 were approximately linear with minimal accumulation with QD dosing. Conversion of LY2979165 to 2812223 was extensive, with minimal LY2979165 measurable in plasma. There was no effect of food on the PK of LY2979165 and 2812223. After 60 mg LY2979165 single‐dose, 2812223 exposure in CSF was approximately 2–6% and plasma exposure and peak concentrations were approximately four‐fold higher than the mGlu2 agonist in vitro EC50 value. No consistent effects were observed on CSF neurotransmitter levels.ConclusionsOral doses of LY2979165 up to 60 mg as a single dose and up to 400 mg given as multiple QD doses, using a titration regimen, were well tolerated with linear PK. Overall, these data support further clinical evaluation of LY2979165.
Math grades and intrinsic motivation in elementary school: A longitudinal investigation of their association
Authors: Weidinger Anne F. , Steinmayr Ricarda , Spinath Birgit 
Published: February 2017

BackgroundIt is often argued that the negative development of intrinsic motivation in elementary school strongly depends on the presence of school grades because grades represent extrinsic consequences and achievement feedback that are supposed to influence intrinsically motivated behaviour. However, only a few studies have tested this hypothesis.AimsTherefore, we investigated the role of school grades in inter‐ and intra‐individual changes in elementary school students’ intrinsic motivation from when grades were first introduced until the end of elementary school, when students in Germany receive recommendations for a secondary school type on the basis of their prior performance in school.SampleA sample of 542 German elementary school students (t1: M = 7.95 years, SD = 0.57) was followed for 2 years from the end of Grade 2 to the end of Grade 4.MethodsAt seven measurement occasions, children's math grades and their domain‐specific intrinsic motivation were assessed.ResultsLatent growth curve models showed differences in trajectories of intrinsic motivation across students rather than uniform development. Moreover, students’ trajectories of grades and intrinsic motivation were only weakly associated. A latent cross‐lagged model revealed that reciprocal effects between the two constructs over time were small at best.ConclusionsContrary to theoretical considerations, our results indicate that negative performance feedback in the form of grades does not necessarily lead to a decrease in intrinsic motivation. This calls into question the common opinion that a perception of being less competent, as reflected by poor grades, is responsible for weakening students’ intrinsic motivation.
Complex Roles of Annexin A2 in Host Blood–Brain Barrier Invasion by Cryptococcus neoformans
Authors: Fang Wei , Fa Zhen‐Zong , Xie Qun , Wang Gui‐Zhen , Yi Jiu , Zhang Chao , Meng Guang‐Xun , Gu Ju‐Lin , Liao Wan‐Qing 
Published: January 2017

SummaryIntroductionFungal transversal across the brain microvascular endothelial cells (BMECs) is the essential step for the development of cryptococcal meningoencephalitis. Annexin A2 (AnxA2) is an important signaling protein involved in several intracellular processes such as membrane trafficking, endocytosis, and exocytosis.AimTo investigate the roles and mechanism of AnxA2 during cryptococcal transversal of BMECs.ResultsCryptococcus neoformans infection initiated upregulation of AnxA2 in mouse BMECs. Blockade with anti‐AnxA2 antibody led to a reduction in fungal transcytosis activity but no change in its adhesion efficiency. Intriguingly, AnxA2 depletion caused a significant increase in fungal association activity but had no effect on their transcytosis. AnxA2 suppression resulted in marked reduction in its partner protein S100A10, and S100A10 suppression in BMECs significantly reduced the cryptococcal transcytosis efficiency. Furthermore, AnxA2 dephosphorylation at Tyr23 and dephosphorylation of downstream cofilin were required for cryptococcal transversal of BMECs, both of which might be primarily involved in the association of C. neoformans with host cells.ConclusionsOur work indicated that AnxA2 played complex roles in traversal of C. neoformans across host BMECs, which might be dependent on downstream cofilin to inhibit fungal adhesion but rely on its partner S100A10 to promote cryptococcal transcytosis.
False‐positive cytopathology results for papillary thyroid carcinoma: A trap for thyroid surgeons
Authors: Yi K.‐I. , Ahn S. , Park D.Y. , Lee J.‐C. , Lee B.‐J. , Wang S.‐G. , Cha W. 
Published: January 2017

AbstractObjectivesCurrent preoperative diagnosis of thyroid nodules remains imperfect despite recent advances in cytopathology and molecular diagnostics. False positivity in preoperative fine‐needle aspiration cytology (FNAC) may lead to overtreatment of patients, including total thyroidectomy, and sometimes to lawsuits for misdiagnosis and malpractice. In this study, we analysed clinical characteristics and pathologic findings in patients with false positivity for papillary thyroid carcinoma (PTC) in FNAC.MethodsWe retrospectively reviewed permanent pathology results from 3788 patients who underwent thyroid surgery. Among them, 48 patients had lesions that were deemed suspicious or positive (Bethesda class V or VI) for PTC in preoperative FNAC. We reviewed clinic–pathologic data, radiologic findings and surgical planning in these patients.ResultsThe prevalence of pathologic thyroiditis was significantly higher among patients with false‐positive FNAC results than in those with confirmed PTC (54.2% vs 9.2%, P<.001). The analysis of the permanent pathology reports showed that 26 patients had chronic lymphocytic thyroiditis and 22 patients had no evidence of thyroiditis. Among the patients without pathologic thyroiditis, 19 patients (86.4%) had nodular hyperplasia and three (13.6%) had follicular adenoma, while among the patients with pathologic thyroiditis, seven (26.9%) had no nodule, 14 (53.8%) had nodular hyperplasia, two (7.7%) had hyalinized nodules, two (7.7%) had follicular adenoma and one (3.8%) had a hyalinizing trabecular tumour. In 42 patients, the extent of surgery (total thyroidectomy or hemithyroidectomy) was to be determined according to the intra‐operative frozen section biopsy results. Among them, four (10.5%) had inconclusive frozen section results, and 38 (90.5%) had benign results on frozen section.ConclusionsPatient counselling about the possibility of false positivity is still important. And the presence of thyroiditis might create confusion in the interpretation of cytopathologic results.
Expanding access to transplantation with hepatitis C‐positive donors: A new perspective on an old issue
Authors: Kling Catherine E. , Limaye Ajit P. , Landis Charles S. , Sibulesky Lena 
Published: January 2017

AbstractWith the need for organs far exceeding supply, donors previously exposed to hepatitis B (HBV) and hepatitis C (HCV) viral infections should be considered for transplantation. Although many centers have protocols for transplanting organs from HBV core antibody‐positive (HBcAb+) donors into select recipients, in the era of direct‐acting antivirals (DAAs), a new focus should be placed on HCV‐positive donors. The transmission rate from HCV antibody‐positive (HCVAb+) nucleic acid testing negative (HCV NAT‐) donors is expected to be very low, and we encourage use of such organs in HCV recipients provided a normal biopsy, appropriate counseling, and careful post‐transplant monitoring. While transmission of HCV from HCV NAT+ donors is universal, the success of DAA in obtaining a sustained viral response in post‐transplant recipients should make the use of these organs more appealing. We herein provide information to help guide the use of organs from HCV donors.
A new and simple method for clarifying the severity of tricuspid regurgitation
Authors: Izgi Ibrahim Akin , Acar Emrah , Kilicgedik Alev , Guler Ahmet , Cakmak Ender Ozgun , Demirel Muhittin , Izci Servet , Yilmaz Mehmet Fatih , Inanir Mehmet , Kirma Cevat 
Published: January 2017

BackgroundNo gold standard exists for grading tricuspid regurgitation (TR) severity. We developed a simple parameter, the right ventricular (RV) early inflow‐outflow (RVEIO) index, using the early diastolic filling velocity and RV outflow velocity integrated over the systolic ejection period. We hypothesized that this index would help identify severe TR in clinical practice.MethodsWe obtained data from routine transthoracic echocardiograms. All records reporting moderate (n=395) or severe (n=395) TR were reanalyzed to measure vena contracta (VC) width, TR jet area, effective regurgitant orifice (EROA) derived with the proximal isovelocity surface area method, RVEIO index, and right‐sided chamber volumes.ResultsSignificant linear trends were demonstrated for right atrial volume index, end‐diastolic volume index, E‐wave velocity, RV velocity time integral, TR jet area, VC width, and EROA with increasing TR severity. Independent predictors of severe RT included RVEIO index ≥ 10, VC width ≥ 0.7 cm, TR jet area>10 cm2, and EROA ≥ 0.4 cm2.ConclusionRVEIO index is a useful, simple, accurate, and independent predictor of severe TR that adds incrementally to traditional methods of quantifying TR severity. Accurate quantification and classification of TR severity is critical for clinical decision‐making and management; therefore, the incorporation of RVEIO index into the integrative approach to grading TR severity should be considered.
Twist deformation for predicting postoperative left ventricular function in patients with mitral regurgitation: A speckle tracking echocardiography study
Authors: Candan Ozkan , Hatipoglu Akpinar Suzan , Dogan Cem , Demirkıran Aykut , Dindar Barış , Bayram Zubeyde , Yılmaz Fatih , Kaymaz Cihangir , Ozdemir Nihal 
Published: January 2017

PurposePostoperative LV dysfunction is associated with poor prognosis and increased mortality in patient with mitral regurgitation undergoing surgery. With this study, we aimed to investigate the predictive value of classic and speckle tracking echocardiographic (STE) LV deformational parameters for estimating postoperative LV dysfunction.MethodsFifty‐nine asymptomatic patients with severe mitral regurgitation (MR) due to mitral valve prolapse, who had sinus rhythm and LV ejection fraction (EF) ≥50%, were included. Patients underwent comprehensive and speckle tracking echocardiographic examination before and 6 months after the surgical procedure. Patients were divided into two groups according to postoperative LV function: group A postoperative LV EF≥50% and group B postoperative LV EF<50%.ResultsPatients in group A were found to have higher LV twist (19.7±6.8° vs 11.9±4.2°; P<.001), LV global longitudinal peak strain (GLPS) (−21.7±4 vs −16.5±3.4%; P<.001), and circumferential strain (−19.5±5.2 vs −14.4±5.1%; P=.004) values but lower end‐systolic diameter (ESD) (3.2±0.6 vs 4.1±0.9 cm; P<.001) when compared to group B. Multivariate logistic regression analysis revealed that GLPS, ESD, and twist were independent predictors of postoperative LV functions. In the ROC analysis, GLPS ≥18.4% and twist>14.4° predicted postoperative LVEF ≥50%.ConclusionGLPS and twist measured by 2DSTE are predictors of LV preservation after surgery in severe MR. These parameters may also be used as prognostic predictors and optimal timing of operation in this patient population.