bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hybrid correction of highly noisy long reads using a variable-order de Bruijn graph
Authors: Morisse Pierre , Lecroq Thierry , Lefebvre Arnaud 
Published: June 2018

AbstractMotivationThe recent rise of long read sequencing technologies such as Pacific Biosciences and Oxford Nanopore allows to solve assembly problems for larger and more complex genomes than what allowed short reads technologies. However, these long reads are very noisy, reaching an error rate of around 10–15% for Pacific Biosciences, and up to 30% for Oxford Nanopore. The error correction problem has been tackled by either self-correcting the long reads, or using complementary short reads in a hybrid approach. However, even though sequencing technologies promise to lower the error rate of the long reads below 10%, it is still higher in practice, and correcting such noisy long reads remains an issue.ResultsWe present HG-CoLoR, a hybrid error correction method that focuses on a seed-and-extend approach based on the alignment of the short reads to the long reads, followed by the traversal of a variable-order de Bruijn graph, built from the short reads. Our experiments show that HG-CoLoR manages to efficiently correct highly noisy long reads that display an error rate as high as 44%. When compared to other state-of-the-art long read error correction methods, our experiments also show that HG-CoLoR provides the best trade-off between runtime and quality of the results, and is the only method able to efficiently scale to eukaryotic genomes.Availability and implementationHG-CoLoR is implemented is C++, supported on Linux platforms and freely available at https://github.com/morispi/HG-CoLoR.Supplementary informationSupplementary data are available at Bioinformatics online.
LncmiRSRN: identification and analysis of long non-coding RNA related miRNA sponge regulatory network in human cancer
Authors: Zhang Junpeng , Liu Lin , Li Jiuyong , Le Thuc Duy 
Published: June 2018

Abstract

Motivation
MicroRNAs (miRNAs) are small non-coding RNAs with the length of ∼22 nucleotides. miRNAs are involved in many biological processes including cancers. Recent studies show that long non-coding RNAs (lncRNAs) are emerging as miRNA sponges, playing important roles in cancer physiology and development. Despite accumulating appreciation of the importance of lncRNAs, the study of their complex functions is still in its preliminary stage. Based on the hypothesis of competing endogenous RNAs (ceRNAs), several computational methods have been proposed for investigating the competitive relationships between lncRNAs and miRNA target messenger RNAs (mRNAs). However, when the mRNAs are released from the control of miRNAs, it remains largely unknown as to how the sponge lncRNAs influence the expression levels of the endogenous miRNA targets.

Results
We propose a novel method to construct lncRNA related miRNA sponge regulatory networks (LncmiRSRNs) by integrating matched lncRNA and mRNA expression profiles with clinical information and putative miRNA-target interactions. Using the method, we have constructed the LncmiRSRNs for four human cancers (glioblastoma multiforme, lung cancer, ovarian cancer and prostate cancer). Based on the networks, we discover that after being released from miRNA control, the target mRNAs are normally up-regulated by the sponge lncRNAs, and only a fraction of sponge lncRNA-mRNA regulatory relationships and hub lncRNAs are shared by the four cancers. Moreover, most sponge lncRNA-mRNA regulatory relationships show a rewired mode between different cancers, and a minority of sponge lncRNA-mRNA regulatory relationships conserved (appearing) in different cancers may act as a common pivot across cancers. Besides, differential and conserved hub lncRNAs may act as potential cancer drivers to influence the cancerous state in cancers. Functional enrichment and survival analysis indicate that the identified differential and conserved LncmiRSRN network modules work as functional units in biological processes, and can distinguish metastasis risks of cancers. Our analysis demonstrates the potential of integrating expression profiles, clinical information and miRNA-target interactions for investigating lncRNA regulatory mechanism.

Availability and implementation
LncmiRSRN is freely available (https://github.com/zhangjunpeng411/LncmiRSRN).

Supplementary information
Supplementary data are available at Bioinformatics online.
A network-based zoning for parallel whole-cell simulation
Authors: Das Barnali , Patil Abhijeet Rajendra , Mitra Pralay 
Published: June 2018

Abstract

Motivation
In Computational Cell Biology, whole-cell modeling and simulation is an absolute requirement to analyze and explore the cell of an organism. Despite few individual efforts on modeling, the prime obstacle hindering its development and progress is its compute-intensive nature. Towards this end, little knowledge is available on how to reduce the enormous computational overhead and which computational systems will be of use.

Results
In this article, we present a network-based zoning approach that could potentially be utilized in the parallelization of whole-cell simulations. Firstly, we construct the protein–protein interaction graph of the whole-cell of an organism using experimental data from various sources. Based on protein interaction information, we predict protein locality and allocate confidence score to the interactions accordingly. We then identify the modules of strictly localized interacting proteins by performing interaction graph clustering based on the confidence score of the interactions. By applying this method to Escherichia coli K12, we identified 188 spatially localized clusters. After a thorough Gene Ontology-based analysis, we proved that the clusters are also in functional proximity. We then conducted Principal Coordinates Analysis to predict the spatial distribution of the clusters in the simulation space. Our automated computational techniques can partition the entire simulation space (cell) into simulation sub-cells. Each of these sub-cells can be simulated on separate computing units of the High-Performance Computing (HPC) systems. We benchmarked our method using proteins. However, our method can be extended easily to add other cellular components like DNA, RNA and metabolites.

Availability and implementation

Supplementary information
Supplementary data are available at Bioinformatics online.
Database of evidence for precision oncology portal
Authors: Sun Sam Q , Mashl R Jay , Sengupta Sohini , Scott Adam D , Wang Weihua , Batra Prag , Wang Liang-Bo , Wyczalkowski Matthew A , Ding Li 
Published: June 2018

Abstract

Summary
A database of curated genomic variants with clinically supported drug therapies and other oncological annotations is described. The accompanying web portal provides a search engine with two modes: one that allows users to query gene, cancer type, variant type or position for druggable mutations, and another to search for and to visualize, on three-dimensional protein structures, putative druggable sites that cluster with known druggable mutations.

Availability and implementation
http://dinglab.wustl.edu/depo
A guide to policy analysis as a research method
Authors: Browne Jennifer , Coffey Brian , Cook Kay , Meiklejohn Sarah , Palermo Claire 
Published: June 2018

SummaryPolicy analysis provides a way for understanding how and why governments enact certain policies, and their effects. Public health policy research is limited and lacks theoretical underpinnings. This article aims to describe and critique different approaches to policy analysis thus providing direction for undertaking policy analysis in the field of health promotion. Through the use of an illustrative example in nutrition it aims to illustrate the different approaches. Three broad orientations to policy analysis are outlined: (i) Traditional approaches aim to identify the ‘best’ solution, through undertaking objective analyses of possible solutions. (ii) Mainstream approaches focus on the interaction of policy actors in policymaking. (iii) Interpretive approaches examine the framing and representation of problems and how policies reflect the social construction of ‘problems’. Policy analysis may assist understanding of how and why policies to improve nutrition are enacted (or rejected) and may inform practitioners in their advocacy. As such, policy analysis provides researchers with a powerful tool to understand the use of research evidence in policymaking and generate a heightened understanding of the values, interests and political contexts underpinning policy decisions. Such methods may enable more effective advocacy for policies that can lead to improvements in health.
Learning optimal opioid prescribing and monitoring: a simulation study of medical residents
Authors: Kannampallil Thomas G , McNutt Robert , Falck Suzanne , Galanter William L , Patterson Dave , Darabi Houshang , Sharabiani Ashkan , Schiff Gordon , Odwazny Richard , Vaida Allen J , Wilkie Diana J , Lambert Bruce L 
Published: June 2018

Abstract

Objective
Hospitalized patients often receive opioids. There is a lack of consensus regarding evidence-based guidelines or training programs for effective management of pain in the hospital. We investigated the viability of using an Internet-based opioid dosing simulator to teach residents appropriate use of opioids to treat and manage acute pain.

Materials and methods
We used a prospective, longitudinal design to evaluate the effects of simulator training. In face-to-face didactic sessions, we taught 120 (108 internal medicine and 12 family medicine) residents principles of pain management and how to use the simulator. Each trainee completed 10 training and, subsequently, 5 testing trials on the simulator. For each trial, we collected medications, doses, routes and times of administration, pain scores, and a summary score. We used mixed-effects regression models to assess the impact of simulation training on simulation performance scores, variability in pain score trajectories, appropriate use of short- and long-acting opioids, and use of naloxone.

Results
Trainees completed 1582 simulation trials (M = 13.2, SD = 6.8), with sustained improvements in their simulated pain management practices. Over time, trainees improved their overall simulated pain management scores (b = 0.05, P &lt; .01), generated lower pain score trajectories with less variability (b = −0.02, P &lt; .01), switched more rapidly from short-acting to long-acting agents (b = −0.50, P &lt; .01), and used naloxone less often (b = −0.10, P &lt; .01).

Discussion and conclusions
Trainees translated their understanding of didactically presented principles of pain management to their performance on simulated patient cases. Simulation-based training presents an opportunity for improving opioid-based inpatient acute pain management.
Inspiring Curiosity and Restoring Humility: The Evolution of Competency-Based Continuing Medical Education
Authors: McMahon Graham T. 
Published: June 2018

Dr. David Price and his colleagues, in their article in this issue of Academic Medicine, summarize the findings from recent studies regarding the association of Maintenance of Certification and physicians’ learning and improvements in care. Their evaluation demonstrates that physicians often changed their practice because of these educational interventions. In this Invited Commentary, the author argues that, although this finding is reassuring, it may be the right answer to the wrong question. The critical questions the profession faces are whether physicians have the humility to routinely submit themselves to the judgment of their peers, whether they will accept responsibility for managing their professional competence and that of their colleagues, and whether they are willing to create a process for identifying and remediating underperforming clinicians.
If certifying boards assume responsibility for this system of accountability, then each would need to set the competency expectations for physicians in its specialty areas, allow clinicians to self-identify their core scope of practice, assume responsibility for summative assessment, provide formative feedback to participants, and link physicians to recommended professional development activities. Continuing certification must be sensitive to the burdens it puts on physicians and recognize engagement in a spectrum of learning activities that are integrated with daily practice, including continuing medical education. By assuming responsibility for their own continuing competency and that of their colleagues, physicians can manifest their commitment to their patients and their profession.
Incisional Nociceptive Input Impairs Attention-related Behavior and Is Associated with Reduced Neuronal Activity in the Prefrontal Cortex in Rats
Authors: Ririe Douglas G. , Boada M. Danilo , MacGregor Megan K. , Martin Salem J. , Strassburg Tracy J. , Kim Susy A. , Eisenach James C. , Martin Thomas J. 
Published: June 2018

Abstract

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background
Cognitive capacity may be reduced from inflammation, surgery, anesthesia, and pain. In this study, we hypothesized that incision-induced nociceptive input impairs attentional performance and alters neuronal activity in the prefrontal cortex.

Methods
Attentional performance was measured in rats by using the titration variant of the 5-choice serial reaction time to determine the effect of surgical incision and anesthesia in a visual attention task. Neuronal activity (single spike and local field potentials) was measured in the medial prefrontal cortex in animals during the task.

Results
Incision significantly impaired attention postoperatively (area under curve of median cue duration-time 97.2 ± 56.8 [n = 9] vs. anesthesia control 25.5 ± 14.5 s-days [n = 9], P = 0.002; effect size, η2 = 0.456). Morphine (1 mg/kg) reduced impairment after incision (area under curve of median cue duration-time 31.6 ± 36.7 [n = 11] vs. saline 110 ± 64.7 s-days [n = 10], P < 0.001; η2 = 0.378). Incision also decreased cell activity (n = 24; 1.48 ± 0.58 vs. control, 2.93 ± 2.02 bursts/min; P = 0.002; η2 = 0.098) and local field potentials (n = 28; η2 = 0.111) in the medial prefrontal cortex.

Conclusions
These results show that acute postoperative nociceptive input from incision reduces attention-related task performance and decreases neuronal activity in the medial prefrontal cortex. Decreased neuronal activity suggests nociceptive input is more than just a distraction because neuronal activity increases during audiovisual distraction with similar behavioral impairment. This suggests that nociceptive input and the medial prefrontal cortex may contribute to attentional impairment and mild cognitive dysfunction postoperatively. In this regard, pain may affect postoperative recovery and return to normal activities through attentional impairment by contributing to lapses in concentration for routine and complex tasks.
Reduced Cerebral Blood Flow in the Visual Cortex and Its Correlation With Glaucomatous Structural Damage to the Retina in Patients With Mild to Moderate Primary Open-angle Glaucoma
Authors: Wang Qian , Chen Weiwei , Qu Xiaoxia , Wang Huaizhou , Wang Ying , Zhang Xun , Li Ting , Wang Ningli , Xian Junfang 
Published: June 2018

Purpose:
Altered ocular and cerebral vascular autoregulation and vasoreactivity have been demonstrated in patients with primary open-angle glaucoma (POAG). In the present study, we investigated the correlations between reduced cerebral blood flow (CBF) in early and higher-tier visual cortical areas and glaucomatous changes in the retinas of patients with mild to moderate POAG.

Patients and Methods:
3-dimensional pseudocontinuous arterial spin labelling magnetic resonance imaging at 3 T was performed in 20 normal controls and 15 mild to moderate POAG patients. Regions of interest were selected based on the Population-Average, Landmark- and Surface-based (PALS) atlas of the human cerebral cortex. Arterial spin labelling–measured CBF values were extracted in the early and higher-tier visual cortical areas and were compared between patients and controls using a 2-sample t test. Pearson correlation analyses were used to assess the correlations between reduced CBF and cup-to-disc ratio, retinal nerve fiber layer thickness, and ganglion cell complex thickness.

Results:
Reduced CBF in early visual cortical areas (V1, V2, and ventral posterior area) and in the higher-tier visual left lateral occipital cortex was presented in mild to moderate POAG patients compared with controls. Furthermore, reduced CBF of the right areas V2 and ventral posterior area was correlated with cup-to-disc ratio, total ganglion cell complex thickness, and average retinal nerve fiber layer thickness.

Conclusions:
In conclusion, the complex pathologic progress of POAG includes abnormal cerebral perfusion within the visual cortex since the mild to moderate disease stages. The association of cerebral perfusion changes with alterations of the optic disc and the retina may contribute to the early diagnosis of POAG.
The new reckoning: The Combat Casualty Care Research Program responds to real and present challenges in military operational projections
Authors: Davis Michael R. , Rasmussen Todd E. , Holcomb Barbara R. 
Published: June 2018

ABSTRACT
This issue of the Journal of Trauma and Acute Care Surgery features topics from the 2017 Military Health System Research Symposium and starts a second decade of partnership between the Combat Casualty Care Research Program (CCCRP) and the journal. This publication comes at a time of significant change for the CCCRP, as it responds to military planning for the future multidomain battlefield (MDB). The projected MDB portends markedly different operational scenarios than those conducted over the past 17 years. Emerging threats around the globe have the Department of Defense preparing for more complex battlefields that are larger in size and scope and which pit the United States against better equipped and more sophisticated adversaries. As the CCCRP navigates this new reckoning associated with trauma care on the MDB, its research investments will need to be robust and enabled to plan, program, and budget for agile and closer-term solutions. To accomplish this, the program will need to expand on its strong foundation of lessons learned and assets developed over the past 20 years.
Incidence, Outcomes, and Long-term Immune Response to Tuberculosis in Organ Transplant Recipients
Authors: Natori Yoichiro , Ferreira Victor H. , Nellimarla Srinivas , Husain Shahid , Rotstein Coleman , Humar Atul , Kumar Deepali 
Published: June 2018

Background
Tuberculosis (TB) is a significant opportunistic infection in solid organ transplant recipients (SOTR). There are limited data on TB incidence in transplantation from low prevalence countries as well as on long-term TB-specific immune responses.

Methods
We performed a single-center retrospective review of SOTR diagnosed with active TB between 2000 and 2015 and further contacted the available patients for a study of long-term T-cell responses using an interferon-gamma (IFN-γ) release assay and a flow cytometry-based assay.

Results
We identified 31 SOTR with active TB for an incidence of 62 cases/100 000 patient-years. Nineteen (61.3%) of 31 patients were diagnosed within the first year after transplant. Nineteen (61.3%) were born in countries with high TB prevalence and disseminated disease occurred in 22.6%. No patient had been screened for latent TB infection pretransplant. The majority of patients received isoniazid and a rifamycin as part of multidrug regimen. In addition, 13 (44.8%) of 29 patients received quinolones. One-year mortality in this population was 19.4%. Eight patients were available for long-term immune responses. Of these, all had detectable IFN-γ response by IFN-γ release assay testing and 7 of 8 had detectable TB-specific T cells, primarily central and effector T-cell responses in the CD4+ compartment and terminally differentiated T cells in the CD8+ compartment.

Conclusions
TB has high incidence in SOTR even in low-prevalence regions but especially targets patients who originated from TB-endemic countries. Long-term TB-specific T-cell responses were found in the majority of patients.
LCM-seq reveals unique transcriptional adaption mechanisms of resistant neurons in spinal muscular atrophy
Authors: Nichterwitz S , Storvall H , Nijssen J , Comley LH , Allodi I , van der Lee M , Schweingruber C , Deng Q , Sandberg R , Hedlund E 
Published: June 2018

AbstractSomatic motor neurons are selectively vulnerable in spinal muscular atrophy (SMA), a lethal disease caused by a deficiency of the ubiquitously expressed survival of motor neuron (SMN) protein. However, some brainstem motor neuron groups, including oculomotor and trochlear (ocular), which innervate the muscles around the eyes, are for unknown reasons spared. Here, using laser capture microdissection coupled with RNA sequencing (LCM-seq), we investigate the transcriptional dynamics in discrete neuronal populations in health and SMA to reveal mechanisms of vulnerability and resistance. Using gene correlation network analysis, we reveal a p53-mediated stress response that is intrinsic to all somatic motor neurons independent of their vulnerability, but absent in resistant red nucleus and visceral motor neurons. However, our temporal and spatial differential expression analysis across neuron types clearly demonstrates that the majority of SMA-induced modulations are cell-type specific. Notably, using gene ontology and protein-network analyses we show that ocular motor neurons present unique disease-adaptation mechanisms that could explain their resilience. In particular, ocular motor neurons up-regulate; i) Syt1, Syt5 and Cplx2, which modulate neurotransmitter release; ii) the motor neuron survival factors Chl1 and Lif, iii) Aldh4, that can protect cells from oxidative stress and iv) the caspase inhibitor Pak4. In conclusion, our in-depth longitudinal analysis of gene expression changes in SMA reveal novel cell-type specific changes that present compelling targets for future gene therapy studies aimed towards preserving vulnerable motor neurons.
Influence of deterministic and stochastic processes on microbial community assembly during aerobic granulation
Authors: Liébana Raquel , Modin Oskar , Persson Frank , Szabó Enikö , Hermansson Malte , Wilén Britt-Marie 
Published: June 2018

ABSTRACTAerobic granular sludge is an energy efficient and compact biofilm process for wastewater treatment which has received much attention during the last decades and is now being implemented in full-scale. However, the factors involved in microbial community assembly during formation of granules are poorly understood and little is known about the reproducibility in treatment performance and community structure. Here we show that both deterministic and stochastic factors exert a dynamic influence during microbial community assembly into granular sludge. During granulation, the microbial communities in three replicate sequencing batch reactors followed similar successional trajectories of the most abundant taxa and showed similar dynamics in diversity. Deterministic factors dominated the assembly of the most abundant community members as the microbial community transitioned from floccular to granular form. Stochastic factors mostly affected rare members of the communities and caused the microbial community structure to diverge in one of the reactors; however, this did not have an impact on the treatment performance. This demonstrates that the reactor function and the dynamics of the most abundant community members are in fact reproducible during the formation of aerobic granules.