bluuebunny/crossref_metadata_2025_split huggingface dataset:
Data Collection for Adverse Events Reporting by US Dental Schools
Authors: Rooney Deborah , Barrett Kimberly , Bufford Blake , Hylen Alexandra , Loomis Matthew , Smith Joshua , Svaan Angela , Pinsky Harold M. , Sweier Domenica 
Published: December 2016

Objectives
Accreditation of US dental schools requires a formal system of quality assessment of clinical adverse events (AE). There is no universal system to collect, record, interpret, or release findings or trends pertaining to AEs. The objective of this study was to compare similarities and differences among the AE reporting forms used at US dental schools.

Methods
Sixteen (24%) dental schools responded to a query to provide copies of their AE forms. The forms were analyzed to identify unique AE items. A total of 69 unique AE items were identified, grouped, and ranked according to frequency. Methods of AE data collection were also noted.

Results
The forms were different in organization, form, and content. The 69 AE items represented a wide variety of information, with no standardization of the type of information, how it was collected, or by whom. We identified 9 most requested AE items and 4 least requested AE items. The schools differed in how the information was obtained: 2 schools used a menu, 8 schools used free response, and 6 schools used a hybrid of both methods.

Conclusions
We found that dental school clinic AE reporting forms are not standardized in structure, organization, or content. We conclude that a hybrid form containing both guided responses and free responses would ensure that proper information is being reported to fully understand why/how an AE occurred. In addition, dental schools need to develop a standardized method of collecting and assessing AE data which will allow for quality improvement and increased patient safety.
Overview on Criteria for MEP Monitoring
Authors: MacDonald David B. 
Published: December 2016

Summary:
Intraoperative motor evoked potentials include the D-wave as a surrogate for long-term motor outcome and muscle motor evoked potentials as a surrogate for early outcome. Their efficacy depends on excluding confounding factors and on warning criteria; insufficiently sensitive criteria could result in unpredicted deficits, whereas excessively sensitive ones could cause false alarms deterring surgical treatment and jading surgeons to alerts, eventually leading to deficits through failure to intervene. Although D-waves have few indications, they are nonsynaptic, linear, and stable—properties that support amplitude reduction criteria: >50% for intramedullary spinal cord tumor surgery and >30% to 40% for peri-Rolandic brain surgery. Muscle motor evoked potentials have many indications but are polysynaptic, nonlinear, and unstable—properties that challenge warning criteria and make them unusually capricious and sensitive. Disappearance is a remarkably frequent pathologic sign compared with other evoked potentials and is always a major criterion. Marked (>80%) amplitude reduction may be a minor or moderate spinal cord criterion, depending on the surgical circumstance. Modest (>50%) reduction may be a major criterion for brain, brainstem, and facial nerve monitoring, if justified by sufficient preceding stability. Acute ≥100-V threshold elevation may be a minor or moderate spinal cord criterion, depending on the surgical circumstance and on adherence to reported methodology. Morphology criteria lack support. Tailoring warning criteria to different monitoring situations based on anatomy, surgical goals, and published evidence seems advisable.
The Interpretation of Muscle Motor Evoked Potentials for Spinal Cord Monitoring
Authors: Kothbauer Karl F. 
Published: December 2016

Objective:
To provide a summary of the intraoperative monitoring of muscle motor evoked potentials (MEPs) based on the presence–absence concept during neurosurgical operations along the spinal cord.

Method:
Expert review.

Discussion:
The measurable parameters of MEPs, such as signal amplitudes and thresholds vary considerably both during a single surgery in a single individual patient as well as between individuals and operations. The presence or absence of responses irrespective of stimulus intensity and response amplitude is much more clearly defined. The correlation of intraoperative MEP data to clinical findings preoperatively and postoperatively so far is best if a presence–absence paradigm is used. The most reliable correlation of postoperative motor deficits is with the disappearance of previously present MEPs, not with the deterioration of amplitudes or the elevation of thresholds. However, in intraoperative decision making an elevation of threshold, without signal loss may still be considered a practical warning sign as it may be a subclinical injury indicator, and may therefore induce a change in surgical strategy. This may be considered a minor warning criterion. A practical concept of the combined use of MEPs with D-wave recordings produced a neurophysiological pattern, which correlates with a reversible motor deficit: Disappearance of MEPs correlates with transient motor deficits if the D-wave amplitude is preserved above an approximate value of 50% of its baseline. Disappearance of the D-wave correlates to paraplegia.

Conclusions:
To date, the best correlation of muscle MEP data to clinical deficits lies in the assessment of disappearance of a previously present MEP regardless of thresholds or amplitudes. Increase in stimulus thresholds for MEPs or to a lesser degree decrement of signal amplitudes may be considered subclinical injury indicators without correlation to neurological dysfunction and thus is considered a minor warning criterion.
The Percentage of Amplitude Decrease Warning Criteria for Transcranial MEP Monitoring
Authors: Journée Henricus L. , Berends Hanneke I. , Kruyt Moyo C. 
Published: December 2016

Summary:
Muscle motor evoked potentials (MEPs) from transcranial electrical stimulation (TES) became a standard technique for monitoring the motor functions of the brain and spinal cord at risk during spinal and brain surgery. However, a wide range of criteria based on the percentage of amplitude decrease is used in practice. A survey of the current literature on clinical outcome parameters reveals a variety of percentages in a range of 30% to 100% (50% to 100% spinal procedures) with no consensus. The interpretation of muscle MEPs is hampered by their sensitivity to many interfering factors. Trial-to-trial MEP variations may partly be reduced by controllable parameters of which TES parameters are in the hands of the neuromonitorist. We propose an operational model based on basic neurophysiologic knowledge to interpret the characteristics of MEP-TES voltage curves and predict the influences of the location on the sigmoid voltage curve on spontaneous MEP-variations and influences of factors affecting the voltage curve. The model predicts a correlation between the slope, expressed by a gain, and variations of muscle MEP amplitudes. This complies with two case examples. The limited specificity/sensitivity of warning criteria based on the percentage of amplitude reduction can possibly be improved by developing standards for set-up procedures of TES paradigms. These procedures include strategies for desensitizing MEPs for variations of controllable parameters. The TES voltage or current is a feasible controlling parameter and should be related to the motor threshold and the onset of the supramaximal level being landmarks of MEP-voltage functions. These parameters may offer a valuable addition to multicenter outcome studies.
Intraoperative Neuromonitoring and Alarm Criteria for Judging MEP Responses to Transcranial Electric Stimulation: The Threshold-Level Method
Authors: Calancie Blair 
Published: December 2016

Summary:
The motor evoked potential (MEP) is used in the operating room to gauge—and ultimately protect—the functional integrity of the corticospinal tract (CST). However, there is no consensus as to how to best interpret the MEP for maximizing its sensitivity and specificity to CST compromise. The most common way is to use criteria associated with response magnitude (response amplitude; waveform complexity, etc.). With this approach, should an MEP in response to a fixed stimulus intensity diminish below some predetermined cutoff, suggesting CST dysfunction, then the surgical team is warned. An alternative approach is to examine the minimum stimulus energy—the threshold—needed to elicit a minimal response from a given target muscle. Threshold increases could then be used as an alternative basis for evaluating CST functional integrity. As the original proponent of this Threshold-Level alarm criteria for MEP monitoring during surgery, I have been asked to summarize the basis for this method. In so doing, I have included justification for what might seem to be arbitrary recommendations. Special emphasis is placed on anesthetic considerations because these issues are especially important when weak stimulus intensities are called for. Finally, it is important to emphasize that all the alarm criteria currently in use for interpreting intraoperative MEPs have been shown to be effective for protecting CST axons during surgery. Although differences between approaches are more than academic, overall it is much better for patient welfare to be using some form of MEP monitoring than to use none at all, while you wait for consensus about alarm criteria to emerge.
Choreography of budding yeast chromosomes during the cell cycle
Authors: Lazar-Stefanita Luciana , Scolari Vittore F. , Mercy Guillaume , Thierry Agnès , Muller Héloise , Mozziconacci Julien , Koszul Romain 
Published: December 2016

AbstractTo ensure the proper transmission of the genetic information, DNA molecules must be faithfully duplicated and segregated. These processes involve dynamic modifications of chromosomes internal structure to promote their individualization, as well as their global repositioning into daughter cells (Guacci et al., 1994; Kleckner et al., 2014; Mizuguchi et al., 2014). In eukaryotes, these events are regulated by conserved architectural proteins, such as structural maintenance of chromosomes (SMCi.e.cohesin and condensin) complexes (Aragon et al., 2013a; Uhlmann, 2016). Although the roles of these factors have been actively investigated, the genome-wide chromosomal architecture and dynamics both at small and large-scales during cell division remains elusive. Here we report a comprehensive Hi-C (Dekker et al., 2002; Lieberman-Aiden et al., 2009) analysis of the dynamic changes of chromosomes structure over theSaccharomyces cerevisiaecell cycle. We uncover specific SMC-dependent structural transitions between the different phases of the mitotic cycle. During replication, cohesion establishment promotes the increase of long-range intra-chromosomal contacts. This process correlates with the individualization of chromosomes, which culminates at metaphase. Mitotic chromosomes are then abruptly reorganized in anaphase by the mechanical forces exerted by the mitotic spindle on the centromere cluster. The formation of a condensin-dependent loop, that bridges centromere cluster with the cenproximal flanking region of the rDNA, suggests that these forces may directly facilitate nucleolus segregation. This work provides a comprehensive overview of chromosome dynamics during the cell cycle of a unicellular eukaryote that recapitulates and unveils new features of highly conserved stages of the cell division.
grID: A CRISPR-Cas9 guide RNA Database and Resource for Genome-Editing
Authors: Jaskula-Ranga Vinod , Zack Donald J. 
Published: December 2016

ABSTRACTCRISPR-Cas9 genome-editing is a revolutionary technology that is transforming biological research. The explosive growth and advances in CRISPR research over the last few years, coupled with the potential for clinical applications and therapeutics, is heralding a new era for genome engineering. To further support this technology platform and to provide a universal CRISPR annotation system, we introduce the grID database (http://crispr.technology), an extensive compilation of gRNA properties including sequence and variations, thermodynamic parameters, off-target analyses, and alternative PAM sites, among others. To aid in the design of optimal gRNAs, the website is integrated with other prominent databases, providing a wealth of additional resources to guide users fromin silicoanalysis through experimental CRISPR targeting. Here, we make available all the tools, protocols, and plasmids that are needed for successful CRISPR-based genome targeting.
Bioorthogonal pro-metabolites for profiling short chain fatty acylation
Authors: Sinclair Wilson R. , Zengeya Thomas T. , Garlick Julie M. , Worth Andrew J. , Blair Ian A. , Snyder Nathaniel W. , Meier Jordan L. 
Published: December 2016

ABSTRACTShort chain fatty acids (SCFAs) play a central role in health and disease. One function of these signaling molecules is to serve as precursors for short chain fatty acylation, a class of metabolically-derived posttranslational modifications (PTMs) that are established by lysine acetyltransferases (KATs) and lysine deacetylases (KDACs). Via this mechanism, short chain fatty acylation serves as an integrated reporter of metabolism as well as KAT and KDAC activity, and has the potential to illuminate the role of these processes in disease. However, few methods to study short chain fatty acylation exist. Here we report a bioorthogonal pro-metabolite strategy for profiling short chain fatty acylation in living cells. Inspired by the dietary component tributyrin, we synthesized a panel of ester-caged bioorthogonal short chain fatty acids. Cellular evaluation of these agents led to the discovery of an azido-ester that is metabolized to its cognate acyl-coenzyme A (CoA) and affords robust protein labeling profiles. We comprehensively characterize the metabolic dependence, toxicity, and histone deacetylase (HDAC) inhibitory activity of these bioorthogonal pro-metabolites, and apply an optimized probe to identify novel candidate protein targets of short chain fatty acids in cells. Our studies showcase the utility of bioorthogonal pro-metabolites for unbiased profiling of cellular protein acylation, and suggest new approaches for studying the signaling functions of SCFAs in differentiation and disease.
Dopamine Negatively Modulates the NCA Ion Channels inC. elegans
Authors: Topalidou Irini , Cooper Kirsten , Pereira Laura , Ailion Michael 
Published: December 2016

AbstractThe NALCN/NCA ion channel is a cation channel related to voltage-gated sodium and calcium channels. NALCN has been reported to be a sodium leak channel with a conserved role in establishing neuronal resting membrane potential, but its precise cellular role and regulation are unclear. TheCaenorhabditis elegansorthologs of NALCN, NCA-1 and NCA-2, act in premotor interneurons to regulate motor circuit activity that sustains locomotion. Recently we found that NCA-1 and NCA-2 are activated by a signal transduction pathway acting downstream of the heterotrimeric G protein Gqand the small GTPase Rho. Through a forward genetic screen, here we identify the GPCR kinase GRK-2 as a new player affecting signaling through the Gq-Rho-NCA pathway. Using structure-function analysis, we find that the GPCR phosphorylation and membrane association domains of GRK-2 are required for its function. Genetic epistasis experiments suggest that GRK-2 acts on the D2-like dopamine receptor DOP-3 to inhibit Gosignaling and positively modulate NCA-1 and NCA-2 activity. Through cell-specific rescuing experiments, we find that GRK-2 and DOP-3 act in premotor interneurons to modulate NCA channel function. Finally, we demonstrate that dopamine, through DOP-3, negatively regulates NCA activity. Thus, this study identifies a pathway by which dopamine modulates the activity of the NCA channels.Author summaryDopamine is a neurotransmitter that acts in the brain by binding seven transmembrane receptors that are coupled to heterotrimeric GTP-binding proteins (G proteins). Neuronal G proteins often function by modulating ion channels that control membrane excitability. Here we identify a molecular cascade downstream of dopamine in the nematodeC. elegansthat involves activation of the dopamine receptor DOP-3, activation of the G protein GOA-1, and inactivation of the NCA-1 and NCA-2 ion channels. We also identify a G protein-coupled receptor kinase (GRK-2) that inactivates the dopamine receptor DOP-3, thus leading to inactivation of GOA-1 and activation of the NCA channels. Thus, this study connects dopamine signaling to activity of the NCA channels through G protein signaling pathways.
Comparison of linear spatial filters for identifying oscillatory activity in multichannel data
Authors: Cohen Michael X 
Published: December 2016

AbstractBackgroundLarge-scale synchronous neural activity produces electrical fields that can be measured by electrodes outside the head, and volume conduction ensures that neural sources can be measured by many electrodes. However, most data analyses in M/EEG research are univariate, meaning each electrode is considered as a separate measurement. Several multivariate linear spatial filtering techniques have been introduced to the cognitive electrophysiology literature, but these techniques are not commonly used; comparisons across filters would be beneficial to the field.New methodThe purpose of this paper is to evaluate and compare the performance of several linear spatial filtering techniques, with a focus on those that use generalized eigendecomposition to facilitate dimensionality reduction and signal-to-noise ratio maximization.ResultsSimulated and empirical data were used to assess the accuracy, signal-to-noise ratio, and interpretability of the spatial filter results. When the simulated signal is powerful, different spatial filters provide convergent results. However, more subtle signals require carefully selected analysis parameters to obtain optimal results.Comparison with existing methodsLinear spatial filters can be powerful data analysis tools in cognitive electrophysiology, and should be applied more often; on the other hand, spatial filters can latch onto artifacts or produce uninterpretable results.ConclusionsHypothesis-driven analyses, careful data inspection, and appropriate parameter selection are necessary to obtain high-quality results when using spatial filters.
When Attended and Conscious Perception Deactivates Fronto-Parietal Regions
Authors: Farooqui Ausaf Ahmed , Manly Tom 
Published: December 2016

AbstractConscious and attended perception is commonly thought to elicit fronto-parietal activity. However, supportive evidence comes largely from studies which involve detecting a target and reporting its visibility. This approach confounds conscious perception with goal completion of either the perceptual task of detection or the metacognitive task of introspective reporting. In contrast, in real life such perceptions are a means of achieving goals and rarely a goal in themselves, and almost never involve explicit metacognitive reports. It therefore remains unclear if fronto-parietal activity is indeed a correlate of conscious perception or is the result of confounds related to goal completion. Here we show that conscious and attended perception when delinked from goals does not increase fronto-parietal activity, and when inconsequential for the goal may even deactivate these regions. In experiments 1 and 2 participants attended to a highly visible stream of letters to detect the occasional targets in their midst. The non-target letters, in spite of being visible and attended to, deactivated fronto-parietal regions. In experiment 3 we looked at the activity elicited by a loud auditory cue that had to be kept in memory for up to 9 s and used to select the correct rule for completing the goal. Even such a salient, attended and remembered event did not elicit prefrontal activity. Across these experiments conscious and attended perception only activated the relevant sensory regions while goal completion events activated fronto-parietal regions.Significance statementConsciousness and attended perception has been seen to correlate with fronto-parietal activity. This informs key theories of consciousness and attention, e.g. widespread availability of incoming information or its higher level representation causes perceptual awareness, or that top down attention during perception broadcasts incoming sensations into frontal and parietal regions. However such experiments unwittingly conflate attended and conscious perception with some form of goal completion, whereas such perception in our daily life mostly serves as a means of goal completion and not a goal in itself. Here we show that such perception when delinked from goal completion does not activate fronto-parietal regions, and may even deactivate these regions if the percept is inconsequential for goal completion.
Convergence of dispersed regulatory mutations predicts driver genes in prostate cancer
Authors: Sallari Richard C. , Sinnott-Armstrong Nicholas A. , French Juliet D. , Kron Ken J. , Ho Jason , Moore Jason H. , Stambolic Vuk , Edwards Stacey L. , Lupien Mathieu , Kellis Manolis 
Published: December 2016

ABSTRACTCancer sequencing predicts driver genes using recurrent protein-altering mutations, but detecting recurrence for non-coding mutations remains unsolved. Here, we present a convergence framework for recurrence analysis of non-coding mutations using three-dimensional co-localization of epigenomically-identified regions. We define the regulatory plexus of each gene as its cell-type-specific three-dimensional gene-regulatory neighborhood, inferred using Hi-C chromosomal interactions and chromatin state annotations. Using 16 matched tumor-normal prostate transcriptomes, we predict tumor-upregulated genes, and find enriched plexus mutations in distal regulatory regions normally repressed in prostate, suggesting out-of-context de-repression. Using 55 matched tumor-normal prostate genomes, we predict 15 driver genes by convergence of dispersed, low-frequency mutations into high-frequency dysregulation events along prostate-specific plexi, while controlling for mutational heterogeneity across regions, chromatin states, and patients. These putative drivers play roles in growth signaling, immune evasion, mitochondrial function, and vascularization, suggesting higher-order pathway-level convergence. We experimentally validate thePLCB4plexus and its ability to affect the canonical PI3K cancer pathway.
Training Genotype Callers with Neural Networks
Authors: Torracinta Remi , Campagne Fabien 
Published: December 2016

ABSTRACTWe present an open source software toolkit for training deep learning models to call genotypes in high-throughput sequencing data. The software supports SAM, BAM, CRAM and Goby alignments and the training of models for a variety of experimental assays and analysis protocols. We evaluate this software in the Illumina Platinum whole genome datasets and find that a deep learning model trained on 80% of the genome achieves a 0.986% accuracy on variants (genotype concordance) when trained with 10% of the data from a genome. The software is distributed athttps://github.com/CampagneLaboratory/variationanalysis. The software makes it possible to train genotype calling models on consumer hardware with CPUs or GPU(s). It will enable individual investigators and small laboratories to train and evaluate their own models and to make open source contributions. We welcome contributions to extend this early prototype or evaluate its performance on other gold standard datasets.