bluuebunny/crossref_metadata_2025 huggingface dataset:
Etiology of recurrent large vessel occlusions treated with repeated thrombectomy
Authors: Ikenberg B , Rösler J , Seifert CL , Wunderlich S , Kaesmacher J , Zimmer C , Boeckh-Behrens T , Friedrich B , Maegerlein C
Published: December 2019

Background

Repeated mechanical thrombectomy for acute stroke treatment in individual patients has been proven feasible. However, less is known about the etiology of recurrent vessel occlusions after prior thrombectomy. We aimed to understand if the etiology of such recurrent events differs from the first stroke.

Methods

Retrospectively, we identified all patients at our center who received a repeated mechanical thrombectomy between 2007 and 2019. Clinical data were retrieved from medical records. Etiology of stroke was evaluated retrospectively, and angiographic studies were revisited.

Results

Twenty-three patients (1.5%) were identified. Median age was 68 years (IQR 56–77). Median NIHSS at first admission was 11 points (IQR 5–15). In nine cases (39.1%), the recurrent vessel occlusion was located exactly at the same position as the prior occlusion. Overall, five (21.7%) patients had a remarkable extracranial pathology as likely cause of stroke recurrence. In 16 patients (69.6%), the etiology of the first stroke and its recurrence was considered as likely being the same, mostly of cardioembolic or unknown origin. In the seven remaining patients (30.4%), the cause of stroke possibly differed from the first event, with five patients (21.7%) having a postinterventional intracranial intimal lesion as possible cause of stroke.

Conclusion

Incidence of repeated thrombectomy was low. However, the high number of patients with known origin of stroke etiology raises the question how their monitoring may be optimized. The number of patients with remarkable extracranial pathologies or intracranial endothelial lesions supports current clinical practice to pay attention to final angiographic series.
Modeling and analysis of carousel-based mixed-model flexible manufacturing system using colored Petri net
Authors: Nabi Hafiz Zahid , Aized Tauseef
Published: December 2019

This study aims to model, analyze, and evaluate performance of a flexible manufacturing system, constituting a carousel-based manufacturing and assembly cells layout, configured to produce mixed-model multiple products employing inter-/intra-cellular routing flexibility in which manufacturing and assembly resources are subject to working and failure modes. A hierarchical colored Petri net model is developed to analyze performance of the flexible manufacturing system. Colored Petri net modeling experiments have been conducted to evaluate the system performance for throughput, cycle time, and work-in-process. The system performance has been investigated in relation to material supply and handling system, process execution, and production resources reliability variables. Different input factors are considered for simulation modeling such as mean machining time, mean loading/unloading time, mean assembly time, buffer capacity, material supply inter-arrival time, number of operations between failures, and mean time to repair for production resources; a variation in input factors has shown a significant impact on system performance measures. The colored Petri net–based modeling, simulation, and analysis approach has been demonstrated as an efficient method for carousel-based mixed-model configured flexible manufacturing system.
Mental workload characteristics of manipulator teleoperators with different spatial cognitive abilities
Authors: Shao Shuyu , Zhou Qianxiang , Liu Zhongqi
Published: December 2019

The main research on manipulator teleoperation includes robust of high-degree of freedom manipulators, sensor measurement accuracy, time delay, and mechanical structure design. Increased mental capacity requirements for complex assignments result in an increased mental workload. Spatial cognitive ability was considered to be the key factor affecting teleoperation performance. To accomplish this, we had 50 participants performed teleoperation while recorded their electroencephalogram. Electroencephalogram data of each task were divided into two periods, which correspond to the observation and large-scale transfer stages of teleoperation, respectively (period 1) and adjust the attitude of the manipulator to approach and align with the target stage (period 2). Brain topographic maps of period 1 (period 1 wavelet packet energy minus resting state wavelet packet energy) and period 2 (period 2 wavelet packet energy minus resting state wavelet packet energy) show that the frontal, central, and occipital regions are the main working areas of low spatial cognitive operators in period 1, while the frontal, central, and occipital regions are the main working areas of high spatial cognitive operators in period 1. The main changes in period 2 were frontal, central, parietal, and occipital regions. This study has implication for the analysis of electroencephalogram signal characteristics of mental workload in different populations to improve operators’ well-being and safety at teleoperation work.
Intravenous antiplatelet therapies (glycoprotein IIb/IIIa receptor inhibitors and cangrelor) in percutaneous coronary intervention: from pharmacology to indications for clinical use
Authors: Capodanno Davide , Milluzzo Rocco P. , Angiolillo Dominick J.
Published: December 2019

Oral antiplatelet drugs are crucially important for patients with acute coronary syndrome or stable coronary artery disease undergoing percutaneous coronary intervention (PCI). In recent decades, several clinical trials have focused on reducing periprocedural ischemic events in patients undergoing PCI by means of more rapid platelet inhibition with the use of intravenous antiplatelet drugs. Glycoprotein IIb/IIIa receptor inhibitors (GPIs) block the final common pathway of platelet aggregation and enable potent inhibition in the peri-PCI period. In recent years, however, the use of GPIs has decreased due to bleeding concerns and the availability of more potent oral P2Y12 inhibitors. Cangrelor is an intravenous P2Y12 receptor antagonist. In a large-scale regulatory trial, cangrelor administration during PCI allowed for rapid, potent and rapidly reversible inhibition of platelet aggregation, with an anti-ischemic benefit and no increase in major bleeding. This article aims to provide an overview of general pharmacology, supporting evidence and current status of intravenous antiplatelet therapies (GPIs and cangrelor), with a focus on contemporary indications for their clinical use.
Re-thinking health literacy: using a capabilities approach perspective towards realising social justice goals
Authors: Pithara Christalla
Published: December 2019

Health literacy has gained popularity as a useful concept to promote and protect health. Even though health literacy research has been prolific it has also been fragmented, facing challenges in achieving its empowerment and social justice-related aims. Crucial limitations make the application of its principles to the health of vulnerable and underrepresented groups problematic, even though these groups are disproportionately affected by ill health. Efforts to refine and make the concept more relevant have tended to expand health literacy models and situate health literacy ‘in context’ to reflect environmental and social factors shaping health literacy. Context-related factors however, have not been consistently embedded in operationalisation and measurement efforts.

This paper argues for health literacy to be re-conceptualised through a capabilities approach lens. It proposes that the capabilities approach can uniquely address the conceptual and methodological criticisms applied to health literacy, whilst encompassing its critical conceptual understandings of health. The advantage of this approach over and above other developments in health literacy theory and practice is its focus on both people’s opportunities or freedoms to achieve desired health-related aims, and their ability to do so. It enables shifting the focus away from health literacy as individual skills and competencies and towards the enabling or inhibiting factors shaping health literacy. A participatory approach is seen as essential for realising this conceptual shift.
Driving performance following a wrist fracture: A pilot study using a driving simulator
Authors: Stinton Susan B , Pappas Evangelos , Edgar Dale W , Moloney Niamh A
Published: December 2019

Introduction

Driving performance, as assessed using a driving simulator, after distal radius fracture has not been previously studied. Our aims were to undertake a pilot study to assess feasibility via: (i) acceptability of driving simulation for this assessment purpose, (ii) recruitment and retention, (iii) sample size calculation. Preliminary evaluations of differences in driving performance between individuals recovering from distal radius fracture and controls were conducted to confirm if the methodology provided meaningful results to aid in justification for future studies.

Methods

Driving performance of 22 current drivers (aged 21–81 years), recruited by convenience sampling, was assessed using a driving simulator. The fracture group included those recovering from distal radius fracture managed with open reduction and internal fixation using a volar plate. The control group were uninjured individuals. Assessment was performed approximately five weeks post-surgery and follow-up assessment two weeks later. Acceptability outcome measures included pain and simulator sickness scores, feasibility measures included retention rates and measures of driving performance included time spent speeding, time spent out of the lane, standard deviation of lateral position and hazard reactions.

Results

The assessment was completed by 91% of participants; two participants dropped out secondary to simulator sickness. Retention rates were 83%. Preliminary results suggest those with distal radius fracture spent more time out of the lane and less time speeding.

Conclusion

This method was sensitive, acceptable and feasible according to the parameters of this pilot study. The results from this small sample suggest that between-group differences in driving performance are measurable using driving simulation five weeks following distal radius fracture.
Are States Under ESSA Prioritizing Education Leadership to Improve Schools?
Authors: De Voto Craig , Reedy Marcy A.
Published: December 2019

This article examines whether states under the Every Student Succeeds Act (ESSA) are prioritizing education leadership to improve schools. Examining all 52 consolidated plans, we found that while the federal law increases states’ flexibility toward such ends, states have taken advantage to varying degrees. We argue that forces at both the state and federal levels are responsible. Recommendations are further discussed as to how the next reauthorization can better address this important link in practice.
Understanding longitudinal biventricular structural and functional changes in a pulmonary hypertension Sugen–hypoxia rat model by cardiac magnetic resonance imaging
Authors: Jayasekera Geeshath , Wilson Kathryn S. , Buist Hanna , Woodward Rosemary , Uckan Aysel , Hughes Colin , Nilsen Margaret , Church A Colin , Johnson Martin K. , Gallagher Lindsay , Mullin James , MacLean Mandy R. , Holmes William M. , Peacock Andrew J. , Welsh David J.
Published: December 2019

Cardiac magnetic resonance‐derived ventricular variables are predictive of mortality in pulmonary arterial hypertension. Rodent models which emphasize ventricular function, allowing serial monitoring, are needed to identify pathophysiological features and novel therapies for pulmonary arterial hypertension. We investigated longitudinal changes in the Sugen–hypoxia model during disease progression. Sprague Dawley rats (n = 32) were divided into two groups. (1) Sugen–hypoxia: a dose of subcutaneous Sugen‐5416 and placed in hypobaric hypoxia for two weeks followed by normoxia for three weeks. (2) Normoxia: maintained at normal pressure for five weeks. Rats were examined at five or eight weeks with right‐heart catheter, cardiac magnetic resonance, and autopsy. Compared to normoxic controls (23.9 ± 4.1 mmHg), right ventricular systolic pressure was elevated in Sugen–hypoxia rats at five and eight weeks (40.9 ± 15.5 mmHg, p = 0.026; 48.9 ± 9.6 mmHg, p = 0.002). Right ventricular end‐systolic volume index was increased in eight weeks Sugen–hypoxia (0.28 ± 0.04 µlcm–2, p = 0.003) compared to normoxic controls (0.18 ±0.03 mlcm–2). There was progressive dilatation of the right ventricular at eight weeks Sugen–hypoxia compared to normoxic controls (0.75 ± 0.13 µlcm–2 vs 0.56 ± 0.1 µlcm–2 p = 0.02). Ventricle mass index by cardiac magnetic resonance at five weeks (0.34 ± 0.06, p = 0.003) and eight weeks Sugen–hypoxia (0.34 ± 0.06, p = 0.002) were higher than normoxic controls (0.21 ± 0.04). Stroke volume, right ventricular ejection fraction, and left ventricular variables were preserved in Sugen–hypoxia. Ventricular changes during the course of illness in a pulmonary arterial hypertension rodent model can be examined by cardiac magnetic resonance. These changes including right ventricular hypertrophy and subsequent dilatation are similar to those seen in pulmonary arterial hypertension patients. Despite the persisting pulmonary hypertension, there are features of adaptive cardiac remodeling through the study duration.
Coping Strategies Used by Female Victims of the Colombian Armed Conflict: The Women in the Colombian Conflict (MUCOCO) Program
Authors: Ubillos-Landa Silvia , Puente-Martínez Alicia , Arias-Rodríguez Gina , Gracia-Leiva Marcela , González-Castro José Luis
Published: December 2019

The effects of armed conflict on women in post-conflict situations are an area of analysis for social disciplines. This study will analyze the situation in Colombia, currently involved in a peace restoration process. The aim is to verify the efficacy of a coping and emotion regulation program analyzing victimization as well as the coping strategies employed in response to these violent acts. The program focuses on 62 women contacted through the Ruta Pacífica de las Mujeres, a nongovernmental organization. The program had a positive effect on women, reporting lower levels of posttraumatic stress, more functional coping strategies, and less use of dysfunctional strategies. All emotional cognitive and social indicators improved. Women felt emotionally better, perceiving greater social support and more trust in institutions. Survivors had more self-confidence to achieve their goals and solve their problems. The implications in a context of peace reconstruction and search for social cohesion are discussed.
The Meaning of Bereavement Following Spousal Loss: A Qualitative Study of the Experiences of Older Adults
Authors: Holm Anne Lise , Severinsson Elisabeth , Berland Astrid Karin
Published: December 2019

Bereavement and spousal loss lead to emotional and practical problems, especially for those in failing health. The aim of this study was to explore the meaning of bereavement in older adults after the death of their spouse. The participants took part in in-depth interviews. The themes and sub-themes were identified using a hermeneutic approach. One overall theme, Struggling to maintain pride and dignity; three themes; and six sub-themes emerged. The first theme, Understanding health decline, included one sub-theme: Difficulty asking for help. The second theme, A lonely painful struggle, had three sub-themes: Striving to avoid feeling sorry for oneself, Searching for meaning when life becomes meaningless, and Sensing that one’s spouse is present. In the third theme, Feeling misunderstood in the dialogue with others, two sub-themes emerged: Longing for support to achieve inclusion and Togetherness is the best medicine. It is vital to prevent older adults from carrying a permanent state of grief with them for the rest of their life.
An Enlightened Environment? Workplace Bullying and Incivility in Irish Higher Education
Authors: Hodgins Margaret , McNamara Patricia Mannix
Published: December 2019

This study explores the experiences of workplace ill-treatment of academic staff in the Irish Higher Education sector, with a focus on organizational response to experienced or witnessed workplace bullying and/or incivility. Workplace bullying is a significant problem, affecting approximately 15% of the workforce, with considerable variation by sector. Educational workplaces typically display prevalence rates that exceed average workplace bullying rates. The negative impacts on health and well-being are well documented and evidence is also emerging to show that organizational responses are less than optimal. The data collected comprise 11 qualitative in-depth interviews with academic staff in three of Ireland’s seven Universities. Applying a phenomenological analysis approach, data revealed that participants’ experiences were overwhelmingly negative in respect of organizational response, despite the fact that each University had an anti-bullying policy. This is explored and discussed in the context of failure to address the complex power relations, which are particularly relevant in professional organizations, intensified by current changes in the higher educational sector. Study limitations include the small number of Universities and small sample size, thus limiting generalizability.
The role of sulfate-rich fluids in heavy rare earth enrichment at the Dashigou carbonatite deposit, Huanglongpu, China
Authors: Cangelosi Delia , Smith Martin , Banks David , Yardley Bruce
Published: December 2019

The Huanglongpu carbonatites are located in the north-western part of the Qinling orogenic belt in central China. Calcite carbonatite dykes at the Dashigou open pit are unusual due to their enrichment in heavy rare earth elements (HREE) relative to light rare earth elements (LREE), leading to a flatREEpattern, and in that the majority of dykes have a quartz core. They also host economic concentrations of molybdenite. The calcite carbonatite dykes show two styles of mineralogy according to the degree of hydrothermal reworking, and these are reflected inREEdistribution and concentration. TheREEin the little-altered calcite carbonatite occur mostly in magmaticREEminerals, mainly monazite-(Ce), and typically have ΣLREE/(HREE+Y) ratios from 9.9 to 17. In hydrothermally altered calcite carbonatites, magmatic monazite-(Ce) is partially replaced to fully replaced byHREE-enriched secondary phases and the rocks have ΣLREE/(HREE+Y) ratios from 1.1 to 3.8. The fluid responsible for hydrothermalREEredistribution is preserved in fluid inclusions in the quartz lenses. The bulk of the quartz lacks fluid inclusions but is cut by two later hydrothermal quartz generations, both containing sulfate-rich fluid inclusions with sulfate typically present as multiple trapped solids, as well as in solution. The estimated total sulfate content of fluid inclusions ranges from 6 to >33 wt.% K2SO4equivalent. We interpret these heterogeneous fluid inclusions to be the result of reaction of sulfate-rich fluids with the calcite carbonatite dykes. The finalHREEenrichment is due to a combination of factors: (1) the progressiveHREEenrichment of later magmatic calcite created aHREE-enriched source; (2)REE–SO42–complexing allowed theREEto be redistributed without fractionation; and (3) secondaryREEmineralisation was dominated by minerals such asHREE-enriched fluorocarbonates, xenotime-(Y) and churchite-(Y) whose crystal structures tends to favourHREE.
Assessment of changes in the brca2 and p53 genes in breast invasive ductal carcinoma in northeast Brazil
Authors: Ramalho Eduardo AVF , Silva-Filho João LQ , Cartaxo Marina FS , Cavalcanti Carmelita BL , Rêgo Moacyr JBM , Oliveira Maria BM , Beltrão Eduardo IC
Published: December 2019

Background

BRCA protein interacts with at least 13 different proteins that have been implicated with cancer susceptibility and loss of BRCA function is correlated to sensitivity to DNA crosslinking agents in preclinical models.

Results

BRCA2 methylation frequency was 44%, p53 Pro22 allele frequency was 32% and heterozygous frequency of Arg/Pro72 genotype was 60% which could be associated as risk factor for metastasis (p = 0.046 OR = 4.190). Regarding to polymorphism of codon 249 the frequency of Arg249 allele presented 82% which was considered not statistically significant.

Conclusions

There was not statistical significance to BRCA2 promoter methylation with any parameters chosen. However, our findings suggest that patients who present heterozygous genotype at codon 72 of p53 gene may have a major susceptibility to any type of metastasis and this could serve as potential auxiliary biomarker for poor prognosis.
Association of serum total bilirubin levels with diastolic dysfunction in heart failure with preserved ejection fraction
Authors: Zheng Huan , Li Ye , Xie Nanzi
Published: December 2019

Background

Left ventricular diastolic dysfunction is one of the main characteristics of heart failure patients with a preserved left ventricular ejection fraction. As bilirubin is regarded as an important endogenous antioxidant molecule, serum total bilirubin levels were compared between heart failure patients with a preserved left ventricular ejection fraction and normal controls in this study. We recruited 327 heart failure patients with a preserved left ventricular ejection fraction and 200 healthy controls. Patients were divided into 4 subgroups by their comprehensive echocardiographic manifestations, 1-mild, 2-moderate, 3-severe (reversible restrictive), 4-severe (fixed restrictive). Total bilirubin levels were compared using stepwise multiple regressions adjusted for selected factors.

Results

After adjusting for gender, age, smoking, systolic blood pressure, diastolic blood pressure, total cholesterol and triglyceride, serum total bilirubin levels were significantly lower in the heart failure group compared with the control group (P < 0.01). Patients in the subgroup (4-severe) showed significantly (P < 0.05) lower levels of total bilirubin when compared with the subgroup (1-mild).

Conclusions

TB level was negatively correlated with left ventricular diastolic dysfunction in heart failure patients with a preserved left ventricular ejection fraction, which might provide a new insight into the complicated mechanisms of heart failure with a preserved left ventricular ejection fraction.
Ranked retrieval of Computational Biology models
Authors: Henkel Ron , Endler Lukas , Peters Andre , Le Novère Nicolas , Waltemath Dagmar
Published: December 2019

Background

The study of biological systems demands computational support. If targeting a biological problem, the reuse of existing computational models can save time and effort. Deciding for potentially suitable models, however, becomes more challenging with the increasing number of computational models available, and even more when considering the models' growing complexity. Firstly, among a set of potential model candidates it is difficult to decide for the model that best suits ones needs. Secondly, it is hard to grasp the nature of an unknown model listed in a search result set, and to judge how well it fits for the particular problem one has in mind.

Results

Here we present an improved search approach for computational models of biological processes. It is based on existing retrieval and ranking methods from Information Retrieval. The approach incorporates annotations suggested by MIRIAM, and additional meta-information. It is now part of the search engine of BioModels Database, a standard repository for computational models.

Conclusions

The introduced concept and implementation are, to our knowledge, the first application of Information Retrieval techniques on model search in Computational Systems Biology. Using the example of BioModels Database, it was shown that the approach is feasible and extends the current possibilities to search for relevant models. The advantages of our system over existing solutions are that we incorporate a rich set of meta-information, and that we provide the user with a relevance ranking of the models found for a query. Better search capabilities in model databases are expected to have a positive effect on the reuse of existing models.
IKKβ inhibitor identification: a multi-filter driven novel scaffold
Authors: Nagarajan Shanthi , Choo Hyunah , Cho Yong Seo , Shin Kye Jung , Oh Kwang-Seok , Lee Byung Ho , Pae Ae Nim
Published: December 2019

Background

Nuclear factor kappa B (NF-κB) is a chief nuclear transcription factor that controls the transcription of various genes; and its activation is tightly controlled by Inhibitor kappa B kinase (IKK). The irregular transcription of NF-κB has been linked to auto-immune disorders, cancer and other diseases. The IKK complex is composed of three units, IKKα, IKKβ, and the regulatory domain NEMO, of which IKKβ is well understood in the canonical pathway. Therefore, the inhibition of IKKβ by drugs forms the molecular basis for anti-inflammatory drug research.

Results

The ligand- and structure-based virtual screening (VS) technique has been applied to identify IKKβ inhibitors from the ChemDiv database with 0.7 million compounds. Initially, a 3D-QSAR pharmacophore model has been deployed to greatly reduce the database size. Subsequently, recursive partitioning (RP) and docking filters were used to screen the pharmacophore hits. Finally, 29 compounds were selected for IKKβ enzyme inhibition assay to identify a novel small molecule inhibitor of IKKβ protein.

Conclusions

In the present investigation, we have applied various computational models sequentially to virtually screen the ChemDiv database, and identified a small molecule that has an IC50 value of 20.3μ M. This compound is novel among the known IKKβ inhibitors. Further optimization of the hit compound can reveal a more potent anti-inflammatory agent.
The study of muscle remodeling in Drosophila metamorphosis using in vivo microscopy and bioimage informatics
Authors: Chinta Rambabu , Tan Joo Huang , Wasser Martin
Published: December 2019

Background

Metamorphosis in insects transforms the larval into an adult body plan and comprises the destruction and remodeling of larval and the generation of adult tissues. The remodeling of larval into adult muscles promises to be a genetic model for human atrophy since it is associated with dramatic alteration in cell size. Furthermore, muscle development is amenable to 3D in vivo microscopy at high cellular resolution. However, multi-dimensional image acquisition leads to sizeable amounts of data that demand novel approaches in image processing and analysis.

Results

To handle, visualize and quantify time-lapse datasets recorded in multiple locations, we designed a workflow comprising three major modules. First, the previously introduced TLM-converter concatenates stacks of single time-points. The second module, TLM-2D-Explorer, creates maximum intensity projections for rapid inspection and allows the temporal alignment of multiple datasets. The transition between prepupal and pupal stage serves as reference point to compare datasets of different genotypes or treatments. We demonstrate how the temporal alignment can reveal novel insights into the east gene which is involved in muscle remodeling. The third module, TLM-3D-Segmenter, performs semi-automated segmentation of selected muscle fibers over multiple frames. 3D image segmentation consists of 3 stages. First, the user places a seed into a muscle of a key frame and performs surface detection based on level-set evolution. Second, the surface is propagated to subsequent frames. Third, automated segmentation detects nuclei inside the muscle fiber. The detected surfaces can be used to visualize and quantify the dynamics of cellular remodeling. To estimate the accuracy of our segmentation method, we performed a comparison with a manually created ground truth. Key and predicted frames achieved a performance of 84% and 80%, respectively.

Conclusions

We describe an analysis pipeline for the efficient handling and analysis of time-series microscopy data that enhances productivity and facilitates the phenotypic characterization of genetic perturbations. Our methodology can easily be scaled up for genome-wide genetic screens using readily available resources for RNAi based gene silencing in Drosophila and other animal models.
TranSeqAnnotator: large-scale analysis of transcriptomic data
Authors: Menon Ranjeeta , Garg Gagan , Gasser Robin B , Ranganathan Shoba
Published: December 2019

Background

The transcriptome of an organism can be studied with the analysis of expressed sequence tag (EST) data sets that offers a rapid and cost effective approach with several new and updated bioinformatics approaches and tools for assembly and annotation. The comprehensive analyses comprehend an organism along with the genome and proteome analysis. With the advent of large-scale sequencing projects and generation of sequence data at protein and cDNA levels, automated analysis pipeline is necessary to store, organize and annotate ESTs.

Results

TranSeqAnnotator is a workflow for large-scale analysis of transcriptomic data with the most appropriate bioinformatics tools for data management and analysis. The pipeline automatically cleans, clusters, assembles and generates consensus sequences, conceptually translates these into possible protein products and assigns putative function based on various DNA and protein similarity searches. Excretory/secretory (ES) proteins inferred from ESTs/short reads are also identified. The TranSeqAnnotator accepts FASTA format raw and quality ESTs along with protein and short read sequences and are analysed with user selected programs. After pre-processing and assembly, the dataset is annotated at the nucleotide, protein and ES protein levels.

Conclusion

TranSeqAnnotator has been developed in a Linux cluster, to perform an exhaustive and reliable analysis and provide detailed annotation. TranSeqAnnotator outputs gene ontologies, protein functional identifications in terms of mapping to protein domains and metabolic pathways. The pipeline is applied to annotate large EST datasets to identify several novel and known genes with therapeutic experimental validations and could serve as potential targets for parasite intervention. TransSeqAnnotator is freely available for the scientific community at http://estexplorer.biolinfo.org/TranSeqAnnotator/.
Matching phosphorylation response patterns of antigen-receptor-stimulated T cells via flow cytometry
Authors: Azad Ariful , Pyne Saumyadipta , Pothen Alex
Published: December 2019

Background

When flow cytometric data on mixtures of cell populations are collected from samples under different experimental conditions, computational methods are needed (a) to classify the samples into similar groups, and (b) to characterize the changes within the corresponding populations due to the different conditions. Manual inspection has been used in the past to study such changes, but high-dimensional experiments necessitate developing new computational approaches to this problem. A robust solution to this problem is to construct distinct templates to summarize all samples from a class, and then to compare these templates to study the changes across classes or conditions.

Results

We designed a hierarchical algorithm,flowMatch, to first match the corresponding clusters across samples for producing robust meta-clusters, and to then construct a high-dimensional template as a collection of meta-clusters for each class of samples. We applied the algorithm on flow cytometry data obtained from human blood cells before and after stimulation with anti-CD3 monoclonal antibody, which is reported to change phosphorylation responses of memory and naive T cells. TheflowMatchalgorithm is able to construct representative templates from the samples before and after stimulation, and to match corresponding meta-clusters across templates. The templates of the pre-stimulation and post-stimulation data corresponding to memory and naive T cell populations clearly show, at the level of the meta-clusters, the overall phosphorylation shift due to the stimulation.

Conclusions

We concisely represent each class of samples by a template consisting of a collection of meta-clusters (representative abstract populations). UsingflowMatch, the meta-clusters across samples can be matched to assess overall differences among the samples of various phenotypes or time-points.
Cell segmentation by multi-resolution analysis and maximum likelihood estimation (MAMLE)
Authors: Chowdhury Sharif , Kandhavelu Meenakshisundaram , Yli-Harja Olli , Ribeiro Andre S
Published: December 2019

Background

Cell imaging is becoming an indispensable tool for cell and molecular biology research. However, most processes studied are stochastic in nature, and require the observation of many cells and events. Ideally, extraction of information from these images ought to rely on automatic methods. Here, we propose a novel segmentation method, MAMLE, for detecting cells within dense clusters.

Methods

MAMLE executes cell segmentation in two stages. The first relies on state of the art filtering technique, edge detection in multi-resolution with morphological operator and threshold decomposition for adaptive thresholding. From this result, a correction procedure is applied that exploits maximum likelihood estimate as an objective function. Also, it acquires morphological features from the initial segmentation for constructing the likelihood parameter, after which the final segmentation is obtained.

Conclusions

We performed an empirical evaluation that includes sample images from different imaging modalities and diverse cell types. The new method attained very high (above 90%) cell segmentation accuracy in all cases. Finally, its accuracy was compared to several existing methods, and in all tests, MAMLE outperformed them in segmentation accuracy.
Widespread evidence of viral miRNAs targeting host pathways
Authors: Carl Joseph W , Trgovcich Joanne , Hannenhalli Sridhar
Published: December 2019

Background

MicroRNAs (miRNA) are regulatory genes that target and repress other RNA molecules via sequence-specific binding. Several biological processes are regulated across many organisms by evolutionarily conserved miRNAs. Plants and invertebrates employ their miRNA in defense against viruses by targeting and degrading viral products. Viruses also encode miRNAs and there is evidence to suggest that virus-encoded miRNAs target specific host genes and pathways that may be beneficial for their infectivity and/or proliferation. However, it is not clear whether there are general patterns underlying cellular targets of viral miRNAs.

Results

Here we show that for several of the 135 known viral miRNAs in human viruses, the human genes targeted by the viral miRNA are enriched for specific host pathways whose targeting is likely beneficial to the virus. Given that viral miRNAs continue to be discovered as technologies evolve, we extended the investigation to 6809 putative miRNAs encoded by 23 human viruses. Our analysis further suggests that human viruses have evolved their miRNA repertoire to target specific human pathways, such as cell growth, axon guidance, and cell differentiation. Interestingly, many of the same pathways are also targeted in mice by miRNAs encoded by murine viruses. Furthermore, Human Cytomegalovirus (CMV) miRNAs that target specific human pathways exhibit increased conservation across CMV strains.

Conclusions

Overall, our results suggest that viruses may have evolved their miRNA repertoire to target specific host pathways as a means for their survival.
An enhanced computational platform for investigating the roles of regulatory RNA and for identifying functional RNA motifs
Authors: Chang Tzu-Hao , Huang Hsi-Yuan , Hsu Justin Bo-Kai , Weng Shun-Long , Horng Jorng-Tzong , Huang Hsien-Da
Published: December 2019

Background

Functional RNA molecules participate in numerous biological processes, ranging from gene regulation to protein synthesis. Analysis of functional RNA motifs and elements in RNA sequences can obtain useful information for deciphering RNA regulatory mechanisms. Our previous work, RegRNA, is widely used in the identification of regulatory motifs, and this work extends it by incorporating more comprehensive and updated data sources and analytical approaches into a new platform.

Methods and results

An integrated web-based system, RegRNA 2.0, has been developed for comprehensively identifying the functional RNA motifs and sites in an input RNA sequence. Numerous data sources and analytical approaches are integrated, and several types of functional RNA motifs and sites can be identified by RegRNA 2.0: (i) splicing donor/acceptor sites; (ii) splicing regulatory motifs; (iii) polyadenylation sites; (iv) ribosome binding sites; (v) rho-independent terminator; (vi) motifs in mRNA 5'-untranslated region (5'UTR) and 3'UTR; (vii) AU-rich elements; (viii) C-to-U editing sites; (ix) riboswitches; (x) RNA cis-regulatory elements; (xi) transcriptional regulatory motifs; (xii) user-defined motifs; (xiii) similar functional RNA sequences; (xiv) microRNA target sites; (xv) non-coding RNA hybridization sites; (xvi) long stems; (xvii) open reading frames; (xviii) related information of an RNA sequence. User can submit an RNA sequence and obtain the predictive results through RegRNA 2.0 web page.

Conclusions

RegRNA 2.0 is an easy to use web server for identifying regulatory RNA motifs and functional sites. Through its integrated user-friendly interface, user is capable of using various analytical approaches and observing results with graphical visualization conveniently. RegRNA 2.0 is now available at http://regrna2.mbc.nctu.edu.tw.
How to inherit statistically validated annotation within BAR+ protein clusters
Authors: Piovesan Damiano , Martelli Pier Luigi , Fariselli Piero , Profiti Giuseppe , Zauli Andrea , Rossi Ivan , Casadio Rita
Published: December 2019

Background

In the genomic era a key issue is protein annotation, namely how to endow protein sequences, upon translation from the corresponding genes, with structural and functional features. Routinely this operation is electronically done by deriving and integrating information from previous knowledge. The reference database for protein sequences is UniProtKB divided into two sections, UniProtKB/TrEMBL which is automatically annotated and not reviewed and UniProtKB/Swiss-Prot which is manually annotated and reviewed. The annotation process is essentially based on sequence similarity search. The question therefore arises as to which extent annotation based on transfer by inheritance is valuable and specifically if it is possible to statistically validate inherited features when little homology exists among the target sequence and its template(s).

Results

In this paper we address the problem of annotating protein sequences in a statistically validated manner considering as a reference annotation resource UniProtKB. The test case is the set of 48,298 proteins recently released by the Critical Assessment of Function Annotations (CAFA) organization. We show that we can transfer after validation, Gene Ontology (GO) terms of the three main categories and Pfam domains to about 68% and 72% of the sequences, respectively. This is possible after alignment of the CAFA sequences towards BAR+, our annotation resource that allows discriminating among statistically validated and not statistically validated annotation. By comparing with a direct UniProtKB annotation, we find that besides validating annotation of some 78% of the CAFA set, we assign new and statistically validated annotation to 14.8% of the sequences and find new structural templates for about 25% of the chains, half of which share less than 30% sequence identity to the corresponding template/s.

Conclusion

Inheritance of annotation by transfer generally requires a careful selection of the identity value among the target and the template in order to transfer structural and/or functional features. Here we prove that even distantly remote homologs can be safely endowed with structural templates and GO and/or Pfam terms provided that annotation is done within clusters collecting cluster-related protein sequences and where a statistical validation of the shared structural and functional features is possible.
The phenylalanine ammonia lyase (PAL) gene family shows a gymnosperm-specific lineage
Authors: Bagal Ujwal R , Leebens-Mack James H , Lorenz W Walter , Dean Jeffrey FD
Published: December 2019

Background

Phenylalanine ammonia lyase (PAL) is a key enzyme of the phenylpropanoid pathway that catalyzes the deamination of phenylalanine to trans-cinnamic acid, a precursor for the lignin and flavonoid biosynthetic pathways. To date, PAL genes have been less extensively studied in gymnosperms than in angiosperms. Our interest in PAL genes stems from their potential role in the defense responses ofPinus taeda, especially with respect to lignification and production of low molecular weight phenolic compounds under various biotic and abiotic stimuli. In contrast to all angiosperms for which reference genome sequences are available,P. taedahas previously been characterized as having only a single PAL gene. Our objective was to re-evaluate this finding, assess the evolutionary history of PAL genes across major angiosperm and gymnosperm lineages, and characterize PAL gene expression patterns inPinus taeda.

Methods

We compiled a large set of PAL genes from the largest transcript dataset available forP. taedaand other conifers. The transcript assemblies forP. taedawere validated through sequencing of PCR products amplified using gene-specific primers based on the putative PAL gene assemblies. Verified PAL gene sequences were aligned and a gene tree was estimated. The resulting gene tree was reconciled with a known species tree and the time points for gene duplication events were inferred relative to the divergence of major plant lineages.

Results

In contrast to angiosperms, gymnosperms have retained a diverse set of PAL genes distributed among three major clades that arose from gene duplication events predating the divergence of these two seed plant lineages. Whereas multiple PAL genes have been identified in sequenced angiosperm genomes, all characterized angiosperm PAL genes form a single clade in the gene PAL tree, suggesting they are derived from a single gene in an ancestral angiosperm genome. The five distinct PAL genes detected and verified inP. taedawere derived from a combination of duplication events predating and postdating the divergence of angiosperms and gymnosperms.

Conclusions

Gymnosperms have a more phylogenetically diverse set of PAL genes than angiosperms. This inference has contrasting implications for the evolution of PAL gene function in gymnosperms and angiosperms.
A Bayesian decision fusion approach for microRNA target prediction
Authors: Yue Dong , Guo Maozu , Chen Yidong , Huang Yufei
Published: December 2019

MicroRNAs (miRNAs) are 19-25 nucleotides non-coding RNAs known to have important post-transcriptional regulatory functions. The computational target prediction algorithm is vital to effective experimental testing. However, since different existing algorithms rely on different features and classifiers, there is a poor agreement among the results of different algorithms. To benefit from the advantages of different algorithms, we proposed an algorithm called BCmicrO that combines the prediction of different algorithms with Bayesian Network. BCmicrO was evaluated using the training data and the proteomic data. The results show that BCmicrO improves both the sensitivity and the specificity of each individual algorithm. All the related materials including genome-wide prediction of human targets and a web-based tool are available at http://compgenomics.utsa.edu/gene/gene_1.php.
Automatically clustering large-scale miRNA sequences: methods and experiments
Authors: Wan Linxia , Ding Jiandong , Jin Ting , Guan Jihong , Zhou Shuigeng
Published: December 2019

Background

Since the initial annotation of microRNAs (miRNAs) in 2001, many studies have sought to identify additional miRNAs experimentally or computationally in various species. MiRNAs act with the Argonaut family of proteins to regulate target messenger RNAs (mRNAs) post-transcriptionally. Currently, researches mainly focus on single miRNA function study. Considering that members in the same miRNA family might participate in the same pathway or regulate the same target(s) and thus share similar biological functions, people can explore useful knowledge from high quality miRNA family architecture.

Results

In this article, we developed an unsupervised clustering-based method miRCluster to automatically group miRNAs. In order to evaluate this method, several data sets were constructed from the online database miRBase. Results showed that miRCluster can efficiently arrange miRNAs (e.g identify 354 families in miRBase16 with an accuracy of 92.08%, and can recognize 9 of all 10 newly-added families in miRBase 17). By far, ~30% mature miRNAs registered in miRBase are unclassified. With miRCluster, over 85% unclassified miRNAs can be assigned to certain families, while ~44% of these miRNAs distributed in ~300novel families.

Conclusions

In short, miRCluster is an automatic and efficient miRNA family identification method, which does not require any prior knowledge. It can be helpful in real use, especially when exploring functions of novel miRNAs. All relevant materials could be freely accessed online (http://admis.fudan.edu.cn/projects/miRCluster).
Enrichment-based DNA methylation analysis using next-generation sequencing: sample exclusion, estimating changes in global methylation, and the contribution of replicate lanes
Authors: Trimarchi Michael P , Murphy Mark , Frankhouser David , Rodriguez Benjamin AT , Curfman John , Marcucci Guido , Yan Pearlly , Bundschuh Ralf
Published: December 2019

Background

DNA methylation is an important epigenetic mark and dysregulation of DNA methylation is associated with many diseases including cancer. Advances in next-generation sequencing now allow unbiased methylome profiling of entire patient cohorts, greatly facilitating biomarker discovery and presenting new opportunities to understand the biological mechanisms by which changes in methylation contribute to disease. Enrichment-based sequencing assays such as MethylCap-seq are a cost effective solution for genome-wide determination of methylation status, but the technical reliability of methylation reconstruction from raw sequencing data has not been well characterized.

Methods

We analyze three MethylCap-seq data sets and perform two different analyses to assess data quality. First, we investigate how data quality is affected by excluding samples that do not meet quality control cutoff requirements. Second, we consider the effect of additional reads on enrichment score, saturation, and coverage. Lastly, we verify a method for the determination of the global amount of methylation from MethylCap-seq data by comparing to a spiked-in control DNA of known methylation status.

Results

We show that rejection of samples based on our quality control parameters leads to a significant improvement of methylation calling. Additional reads beyond ~13 million unique aligned reads improved coverage, modestly improved saturation, and did not impact enrichment score. Lastly, we find that a global methylation indicator calculated from MethylCap-seq data correlates well with the global methylation level of a sample as obtained from a spike-in DNA of known methylation level.

Conclusions

We show that with appropriate quality control MethylCap-seq is a reliable tool, suitable for cohorts of hundreds of patients, that provides reproducible methylation information on a feature by feature basis as well as information about the global level of methylation.