bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transition to a new electronic health record and pediatric medication safety: lessons learned in pediatrics within a large academic health system
Authors: Whalen Kimberly , Lynch Emily , Moawad Iman , John Tanya , Lozowski Denise , Cummings Brian M 
Published: March 2018

Abstract

Objective
While the electronic health record (EHR) has become a standard of care, pediatric patients pose a unique set of risks in adult-oriented systems. We describe medication safety and implementation challenges and solutions in the pediatric population of a large academic center transitioning its EHR to Epic.

Methods
Examination of the roll-out of a new EHR in a mixed neonatal, pediatric and adult tertiary care center with staggered implementation. We followed the voluntarily reported medication error rate for the neonatal and pediatric subsets and specifically monitored the first 3 months after the roll-out of the new EHR. Data was reviewed and compiled by theme.

Results
After implementation, there was a 5-fold increase in the overall number of medication safety reports; by the third month the rate of reported medication errors had returned to baseline. The majority of reports were near misses. Three major safety themes arose: (1) enterprise logic in rounding of doses and dosing volumes; (2) ordering clinician seeing a concentration and product when ordering medications; and (3) the need for standardized dosing units through age contexts created issues with continuous infusions and pump library safeguards.

Conclusions
Future research and work need to be focused on standards and guidelines on implementing an EHR that encompasses all age contexts.
Scarring At Donor Sites After Split-Thickness Skin Graft: A Prospective, Longitudinal, Randomized Trial
Authors: Karlsson Matilda , Elmasry Moustafa , Steinvall Ingrid , Sjöberg Folke , Olofsson Pia , Thorfinn Johan 
Published: March 2018

ABSTRACT

OBJECTIVE:
The aim of this study was to evaluate scarring at split-thickness skin graft donor sites 8 years after surgery.

METHODS:
At surgery, 67 patients were randomized to hydrofiber, polyurethane foam, or porcine xenograft treatment. Scars were evaluated with the Patient and Observer Scar Assessment Scale.

RESULTS:
Results showed significant differences in observed scar outcomes at donor sites, leaving the polyurethane foam–treated and the porcine xenograft–treated patients with the least satisfying scars. Multivariable regression analysis showed that the group treated with the xenografts had worse scores for overall opinion of the scar than did the other groups (P = .03), the most important factor being pigmentation. There was no correlation between duration of healing time and quality of the scar.

CONCLUSIONS:
There were significant differences among the groups, with the hydrofiber group being the most satisfied with the appearance of their scar.
Endotypes in allergic diseases
Authors: Agache Ioana , Rogozea Liliana 
Published: March 2018

Purpose of review
The precision medicine concept is both appealing and challenging. We review here the recent findings in the endotype-driven approach for major allergic diseases.

Recent findings
Stratified medicine for different allergic diseases can identify patients who are more likely to benefit or experience an adverse reaction in response to a given therapy and anticipate their long-term outcome and vital risk. In addition, this approach potentially facilitates drug development and prevention strategies.

Summary
The endotype-driven approach in allergic diseases has tremendous potential, but there are notable barriers in reaching the new world of precision medicine. Multidimensional endotyping integrating visible properties with multiple biomarkers is recommended for both type 2 and nontype 2 allergic diseases to provide evidence that a certain pathway is the key driver for a given patient. Significant healthcare system changes are required to achieve the expected targets.
A Review of the Impact of Obstetric Anesthesia on Maternal and Neonatal Outcomes
Authors: Lim Grace , Facco Francesca L. , Nathan Naveen , Waters Jonathan H. , Wong Cynthia A. , Eltzschig Holger K. 
Published: March 2018

Abstract
Obstetric anesthesia has evolved over the course of its history to encompass comprehensive aspects of maternal care, ranging from cesarean delivery anesthesia and labor analgesia to maternal resuscitation and patient safety. Anesthesiologists are concerned with maternal and neonatal outcomes, and with preventing and managing complications that may present during childbirth. The current review will focus on recent advances in obstetric anesthesia, including labor anesthesia and analgesia, cesarean delivery anesthesia and analgesia, the effects of maternal anesthesia on breastfeeding and fever, and maternal safety. The impact of these advances on maternal and neonatal outcomes is discussed. Past and future progress in this field will continue to have significant implications on the health of women and children.
Creation of a Central Under Flap Pocket Allows Secondary Implant Augmentation of Perforator Flap Breast Reconstruction
Authors: Blum Craig A. , DellaCroce Frank J. , Sullivan Scott K. , Trahan Chris , Wise M. Whitten 
Published: March 2018

Background:
When a single perforator flap does not provide adequate volume or projection for satisfactory breast reconstruction, the addition of an implant may be considered at the time of second-stage revisions. Dissection of an implant pocket beneath the flap may lead to the inadvertent injury of the flap pedicle as the tissue planes have been obscured by tissue ingrowth. The authors present a technique in which the boundaries of the implant pocket are predetermined at the time of flap reconstruction allowing an implant to be inserted at the second stage in ideal position with greater ease of dissection and minimal risk to the flap pedicle.

Methods:
Forty patients (80 bilateral perforator flap breast reconstructions) treated with the creation of central under flap pocket technique in anticipation of subsequent sub flap implant augmentation within an 18-month period were assessed retrospectively.

Results:
Sixty-eight patients with flaps (85%) went on to receive secondary augmentation with silicone implants. The average percentage increase in volume contributed by the implant was 41%. The undersurface of the acellular dermal matrix was readily identified, and its medial most extent safely determined, allowing the expeditious recreation of the predelineated central under-flap implant pocket. No flap pedicles were injured during the process, and the implants were placed in a favorable position providing maximum projection to the reconstruction. No subsequent development of fat necrosis was identified after augmentation.

Conclusion:
The creation of central under flap pocket technique allows for safe, effective, and expedient delayed implant augmentation of perforator flap breast reconstruction.
Optic Disc Features in Highly Myopic Eyes: The ZOC-BHVI High Myopia Cohort Study
Authors: Li Zhixi , Guo Xinxing , Xiao Ou , Lee Pei Ying , Liu Ran , Wang Decai , Sankaridurg Padmaja , He Mingguang 
Published: March 2018

SIGNIFICANCE
Some studies reported that optic disc tilt and rotation might be risk factors for the susceptibility of high myopic eyes to develop glaucoma. However, data regarding optic disc manifestations in high myopia participants are few. It is crucial to characterize the features of optic disc manifestations among high myopes.

PURPOSE
To describe optic disc characteristics of Chinese highly myopic eyes and to investigate associated factors.

METHODS
This cross-sectional, observational study included 890 Chinese with bilateral high myopia (defined as ≤−6.00 diopters spherical power) in 2012. All subjects underwent cycloplegic autorefraction, ocular biometry, and fundus photography. The optic disc tilt ratio, degree of rotation, and β-zone peripapillary atrophy area were measured from the 45°optic disc-centered fundus photographs. Optic disc tilt was defined as optic disc tilt ratio, the ratio of maximum to minimum diameter of optic disc, exceeding 1.3. The definition of optic disc rotation was using optic disc rotation degree, the angle from long diameter and the vertical meridian, of >15°.

RESULTS
Among 890 participants, 2 were excluded by ungradable optic disc-centered fundus photographs. In the 888 studied right eyes, the mean spherical power was −9.36 ± 3.46 diopters with a mean axial length of 27.51 ± 1.63 mm. The proportion of optic disc tilting, rotation, and β-zone peripapillary atrophy were 81.2%, 48.3%, and 92.8%, respectively. The mean ratio of optic disc tilting and rotation degree was 1.78 ± 0.53 and 21.08 ± 19.91°; the mean area of β-zone peripapillary atrophy/optic disc head was 1.11 ± 1.22. A multiple linear regression showed that older age (P < .001), female (P = .02), and more myopic spherical equivalent (P = .005) were related to the greater optic disc tilting ratio.

CONCLUSIONS
Beta-zone peripapillary atrophy, optic disc tilting, and rotation are very common in highly myopic eyes in Chinese population. Older age, female, and more myopic spherical equivalent are risk factors of higher degree of optic disc tilting.
Congenital Achiasma
Authors: Lecler Augustin , Attye Arnaud , Edelson Catherine 
Published: March 2018

Abstract:
In evaluating a 3-month-old boy with horizontal nystagmus, brain MRI revealed absence of the optic chiasm. The remainder of the brain was normal in appearance. Achiasma was confirmed with diffusion tensor imaging and best visualized with optimized probabilistic-based tractography.
Regional protein expression in human Alzheimer’s brain correlates with disease severity
Authors: Xu Jingshu , Patassini Stefano , Rustogi Nitin , Riba-Garcia Isabel , Hale Benjamin D. , Phillips Alexander M , Waldvogel Henry , Haines Robert , Bradbury Phil , Stevens Adam , Faull Richard L. M. , Dowsey Andrew W. , Cooper Garth J. S. , Unwin Richard D. 
Published: March 2018

AbstractAlzheimer’s disease (AD) is a progressive neurodegenerative disorder that currently affects 36 million people worldwide with no effective treatment available. Development of AD follows a distinctive pattern in the brain and is poorly modelled in animals. Therefore, it is vital to widen both the spatial scope of the study of AD and prioritise the study of human brains. Here we show that functionally distinct human brain regions show varying and region-specific changes in protein expression. These changes provide novel insights into the progression of disease, novel AD-related pathways, the presence of a ‘gradient’ of protein expression change from less to more affected regions, and the presence of a ‘protective’ protein expression profile in the cerebellum. This spatial proteomics analysis provides a framework which can underpin current research and opens new avenues of interest to enhance our understanding of molecular pathophysiology of AD, provides new targets for intervention and broadens the conceptual frameworks for future AD research.
Differential encoding of predator fear in the ventromedial hypothalamus and periaqueductal grey
Authors: Masferrer Maria Esteban , Silva Bianca A. , Nomoto Kensaku , Lima Susana Q. , Gross Cornelius T. 
Published: March 2018

AbstractThe ventromedial hypothalamus is a central node of the mammalian predator defense network. Stimulation of this structure in rodents and primates elicits abrupt defensive responses, including flight, freezing, sympathetic activation, and panic, while inhibition reduces defensive responses to predators. The major efferent target of the ventromedial hypothalamus is the dorsal periaqueductal grey, and stimulation of this structure also elicits flight, freezing, and sympathetic activation. However, reversible inhibition experiments suggest that the ventromedial hypothalamus and periaqueductal grey play distinct roles in the control of defensive behavior, with the former proposed to encode an internal state necessary for the motivation of defensive responses, while the latter serves as a motor pattern initiator. Here we used electrophysiological recordings of single units in behaving mice exposed to a rat to investigate the encoding of predator fear in the dorsomedial division of the ventromedial hypothalamus and the dorsal periaqueductal grey. Distinct correlates of threat intensity and motor responses were found in both structures, suggesting a distributed encoding of sensory and motor features in the medial hypothalamic-brainstem instinctive network.
Targeting of NF-κB to Dendritic Spines is Required for Synaptic Signaling and Spine Development
Authors: Dresselhaus Erica C. , Boersma Matthew C.H. , Meffert Mollie K. 
Published: March 2018

ABSTRACTLong-term forms of brain plasticity share a requirement for changes in gene expression induced by neuronal activity. Mechanisms that determine how the distinct and overlapping functions of multiple activity-responsive transcription factors, including nuclear factor kappa B (NF-κB), give rise to stimulus-appropriate neuronal responses remain unclear. We report that the p65/RelA subunit of NF-κB confers subcellular enrichment at neuronal dendritic spines and engineer a p65 mutant that lacks spine-enrichment (ΔSEp65) but retains inherent transcriptional activity equivalent to wild-type p65. Wild-type p65 or ΔSEp65 both rescue NF-κB-dependent gene expression in p65-deficient murine hippocampal neurons responding to diffuse (PMA/ionomycin) stimulation. In contrast, neurons lacking spine-enriched NF-κB are selectively impaired in NF-κB-dependent gene expression induced by elevated excitatory synaptic stimulation (bicuculline or glycine). We used the setting of excitatory synaptic activity during development that produces NF-κB-dependent growth of dendritic spines to test physiological function of spine-enriched NF-κB in an activity-dependent response. Expression of wild-type p65, but not ΔSEp65, is capable of rescuing spine density to normal levels in p65-deficient pyramidal neurons. Collectively, these data reveal that spatial localization in dendritic spines contributes unique capacities to the NF-κB transcription factor in synaptic activity-dependent responses.SIGNIFICANCE STATEMENTExtensive research has established a model in which the regulation of neuronal gene expression enables enduring forms of plasticity and learning. However, mechanisms imparting stimulus-specificity to gene regulation, insuring biologically appropriate responses, remain incompletely understood. NF-κB is a potent transcription factor with evolutionarily-conserved functions in learning and the growth of excitatory synaptic contacts. Neuronal NF-κB is localized in both synapse and somatic compartments, but whether the synaptic pool of NF-κB has discrete functions is unknown. This study reveals that NF-κB enriched in dendritic spines (the postsynaptic sites of excitatory contacts) is selectively required for NF-κB activation by synaptic stimulation and normal dendritic spine development. These results support spatial localization at synapses as a key variable mediating selective stimulus-response coupling.
Mathematical modelling of molecular heterogeneity identifies novel markers and subpopulations in complex tumors
Authors: Chen Lulu , Wang Niya , Clarke Robert , Zhang Zhen , Wang Yue 
Published: March 2018

AbstractIntratumor heterogeneity, as both a major confounding factor and an underexploited information source, is widely implicated as a key driver of drug resistance. While a handful of reports have demonstrated the potential of supervised methods to deconvolute intratumor heterogeneity, these approaches require a priori information on the marker genes or composition of known subpopulations. To address the critical problem of the absence of validated marker genes for many (including novel) subpopulations, we developed convex analysis of mixtures (CAM), a fully unsupervised deconvolution method, for identifying marker genes and subpopulations directly from original mixed molecular expressions.
Nonlinear functional responses and ecological pleiotropy alter the strength of disruptive selection in consumers
Authors: Coblentz Kyle E. 
Published: March 2018

AbstractMuch of the theory on disruptive selection has focused on selection in generalist consumers caused by ecological opportunity through the availability of alternative resources and intraspecific competition for those resources. This theory, however, makes several ecologically unrealistic assumptions. First, this theory assumes that consumers have a linear, resource-dependent functional response, ignoring well-documented effects of resource handling times and consumer dependence. Second, this theory assumes that the trait under selection only influences the percapita attack rates of the consumer, ignoring other effects of the trait that may influence feeding rates and hence fitness. Here, I develop a one consumer-two resource model to investigate how nonlinear functional responses and ecological pleiotropy (traits that have multiple simultaneous ecological effects) influence the strength of disruptive selection. I find that handling times and interference among consumers are capable of altering disruptive selection by changing feeding rates differentially across consumer phenotypes. In particular, handling times cause a decrease in the strength of disruptive selection while the effects of interference depend on the mechanism through which interference occurs. The effects of handling times and interference, however, are dependent on whether and how ecological pleiotropy causes correlations between handling times or interference rates and attack rates. Overall, my results suggest that features defining the functional responses of consumers and the relationships among those features determine the likelihood and strength of disruptive selection. In particular, disruptive selection should be strongest in generalist populations composed of individual diet specialists who experience lower handling times and interference rates on the resources for which their attack rates are highest.
Population dynamics of choice representation in dorsal premotor and primary motor cortex
Authors: Peixoto Diogo , Kiani Roozbeh , Chandrasekaran Chandramouli , Ryu Stephen I. , Shenoy Krishna V. , Newsome William T. 
Published: March 2018

SummaryStudies in multiple species have revealed the existence of neural signals that lawfully co-vary with different aspects of the decision-making process, including choice, sensory evidence that supports the choice, and reaction time. These signals, often interpreted as the representation of a decision variable (DV), have been identified in several motor preparation circuits and provide insight about mechanisms underlying the decision-making process. However, single-trial dynamics of this process or its representation at the neural population level remain poorly understood. Here, we examine the representation of the DV in simultaneously recorded neural populations of dorsal premotor (PMd) and primary motor (M1) cortices of monkeys performing a random dots direction discrimination task with arm movements as the behavioral report. We show that single-trial DVs covary with stimulus difficulty in both areas but are stronger and appear earlier in PMd compared to M1 when the stimulus duration is fixed and predictable. When temporal uncertainty is introduced by making the stimulus duration variable, single-trial DV dynamics are accelerated across the board and the two areas become largely indistinguishable throughout the entire trial. These effects are not trivially explained by the faster emergence of motor kinematic signals in PMd and M1. All key aspects of the data were replicated by a computational model that relies on progressive recruitment of units with stable choice-related modulation of neural population activity. In contrast with several recent results in rodents, decision signals in PMd and M1 are not carried by short sequences of activity in non-overlapping groups of neurons but are instead distributed across many neurons, which once recruited, represent the decision stably during individual behavioral epochs of the trial.
Glutamatergic facilitation of neural responses in MT enhances motion perception in humans
Authors: Schallmo Michael-Paul , Millin Rachel , Kale Alex M. , Kolodny Tamar , Edden Richard A.E. , Bernier Raphael A. , Murray Scott O. 
Published: March 2018

AbstractThere is large individual variability in human neural responses and perceptual abilities. The factors that give rise to these individual differences, however, remain largely unknown. To examine these factors, we separately measured fMRI responses to moving gratings in the motion-selective region MT, and perceptual duration thresholds for motion direction discrimination within the same group of male and female subjects. Further, we acquired MR spectroscopy data that allowed us to quantify an index of neurotransmitter levels in the region surrounding MT. We show that individual differences in the Glx (glutamate + glutamine) signal in the MT region are associated with both higher fMRI responses and improved psychophysical task performance. Our results suggest that individual differences in baseline levels of glutamate within MT contribute to motion perception by increasing neural responses in this region.SignificanceWhat factors govern the relationship between neural activity and behavior? Our results suggest that one such factor is the level of glutamate, an excitatory neurotransmitter, within a particular region of cortex. By measuring an index of glutamate in vivo using magnetic resonance spectroscopy, we show that human subjects with more glutamate in the visual motion area known as MT also have larger fMRI responses (an index of neural activity) in this region. Further, people with more glutamate in MT can accurately perceive moving images presented more briefly within a behavioral task. Our findings point to an important role for glutamate levels in determining the relationship between neural responses and behavior during visual motion perception.
Switch-like activation of Bruton’s tyrosine kinase by membrane-mediated dimerization
Authors: Chung Jean K. , Nocka Laura M. , Wang Qi , Kadlecek Theresa A. , Weiss Arthur , Kuriyan John , Groves Jay T. 
Published: March 2018

ABSTRACTThe transformation of molecular binding events into cellular decisions is the basis of most biological signal transduction. A fundamental challenge faced by these systems is that protein-ligand chemical affinities alone generally result in poor sensitivity to ligand concentration, endangering the system to error. Here, we examine the lipid-binding pleckstrin homology and Tec homology (PH-TH) module of Bruton’s tyrosine kinase (Btk) Using fluorescence correlation spectroscopy (FCS) and membrane-binding kinetic measurements, we identify a self-contained phosphatidylinositol (3,4,5)-trisphosphate (PIP3) sensing mechanism that achieves switch-like sensitivity to PIP3 levels, surpassing the intrinsic affinity discrimination of PIP3:PH binding. This mechanism employs multiple PIP3 binding as well as dimerization of Btk on the membrane surface. Mutational studies in live cells confirm that this mechanism is critical for activation of Btk in vivo. These results demonstrate how a single protein module can institute a minimalist coincidence detection mechanism to achieve high-precision discrimination of ligand concentration.