bluuebunny/crossref_metadata_2025_split huggingface dataset:
How to translate the new hospital-acquired and ventilator-associated pneumonia guideline to the bedside
Authors: Perez Mario F. , Metersky Mark L. , Kalil Andre C. 
Published: July 2017

Purpose of review
Hospital-acquired pneumonia and ventilator-associated pneumonia remain significant causes of morbidity, mortality, and financial burden in the United States and around the globe. Although guidelines for the management of patients with these conditions have been available for several years, implementation remains challenging. Here, we review the most common barriers faced by clinicians in implementing the current guidelines and offer suggestions for improved adherence.

Recent findings
Recent studies have identified barriers to the implementation of the guidelines regarding management of hospital-acquired and ventilator-associated pneumonia. The most common difficulties encountered are lack of awareness of the guidelines, practice variation among providers delivering care to affected patients, lack of antibiogram information, and lack of antibiotic stewardship programs.

Summary
Translating the current hospital-acquired and ventilator-associated pneumonia guidelines to the bedside requires understanding of the current barriers affecting care of patients with these conditions. Adopting clinical guidelines facilitates the management of these patients and improves outcomes. Dissemination of the guidelines, provider education, antibiotic stewardship programs, access to local antibiogram information, audit and feedback, electronic tools and leadership commitment are likely to play important roles in guideline implementation. More studies on hospital-acquired and ventilator-associated pneumonia guideline implementation are necessary to identify the most effective interventions.
Pharyngolaryngeal symptoms associated with thyroid disease
Authors: Nam Inn-Chul , Park Young-Hak 
Published: July 2017

Purpose of review
The current review summarizes previous reports on laryngopharyngeal symptoms associated with thyroid disease. This review also includes pharyngolaryngeal symptoms caused by thyroidectomy. However, we focus on pharyngolaryngeal symptoms following uncomplicated thyroidectomy, as this is an important issue in the fields of otolaryngology.

Recent findings
An enlarged thyroid gland, as in thyroiditis, multinodular goiter, or large nodules, can cause compressive symptoms. Malignant nodules invading the recurrent laryngeal nerve and benign nodules compressing the nerve can cause vocal cord paralysis and hoarseness. Pharyngolaryngeal symptoms are known to develop after a thyroidectomy, generally as a result of injury to the superior or recurrent laryngeal nerve. However, recent studies have shown that various pharyngolaryngeal symptoms, such as globus symptoms and voice changes, occur after thyroidectomy in the absence of laryngeal nerve injury. These symptoms are known collectively as postthyroidectomy syndrome. Several possible explanations have been proposed and evaluated for postthyroidectomy syndrome.

Summary
Several thyroid disorders can cause compressive symptoms and hoarseness. Superior and/or recurrent laryngeal nerve injury during thyroidectomy is the main cause of various pharyngolaryngeal symptoms. However, other pharyngolaryngeal symptoms that arise following thyroidectomy in the absence of nerve injury, a condition known as postthyroidectomy syndrome, are becoming more common.
Genetic causes of sudden cardiac death in children: inherited arrhythmogenic diseases
Authors: Vacanti Gaetano , Maragna Riccardo , Priori Silvia G. , Mazzanti Andrea 
Published: July 2017

Purpose of review
In this chapter we will discuss the most recent and relevant evidences published in the field of inherited arrhythmogenic disorders, focusing on the so called ‘channelopathies’ that are associated with sudden cardiac death (SCD) in children: long QT syndrome (LQTS), short QT syndrome (SQTS), Brugada syndrome (BrS), and catecholaminergic polymorphic ventricular tachycardia (CPVT).

Recent findings
We will discuss the latest diagnostic criteria for channelopathies released by the European Society of Cardiology, the new data on BrS in children and the recent evidence supporting a genotype-specific therapy for LQTS type 3. Moreover, we will present further insights into the risk stratification of the children affected by LQTS, analyzing the role of imaging for the prediction of life-threatening arrhythmias. In addition, we will offer a perspective on how to deal with genetic results in families affected by SCD at very young ages.

Summary
The selected publications will aid pediatricians in their clinical work when managing little patients with inherited arrhythmias, providing the most recent information for diagnosis, risk stratification, and management.
Interventions Using Social Media for Cancer Prevention and Management
Authors: Han Claire Jungyoun , Lee Young Ji , Demiris George 
Published: July 2017

Background:
Regarding cancer awareness, social media effectively promotes health and supports self-management. Given the diverse study designs, methodologies, and approaches of social media interventions in oncology, it is difficult to determine the effects of social media on cancer prevention and management.

Objective:
We aim to systematically review intervention studies using social media for cancer care.

Methods:
A systematic search, using 7 electronic databases (PubMed, Web of Science, CINAHL, Cochrane Library, Scopus, EMBASE, and PsycINFO), was conducted to identify surveys and interventions using contemporary social media tools with a focus on cancer.

Results:
Of the 18 selected studies, 7 were randomized controlled trials. Most studies were conducted for all types of cancer, and some were conducted for breast cancer in the United States, with mostly white female participants. Facebook was the most frequently used platform. Most studies targeted healthy participants providing cancer prevention education. With social media platforms as part of a larger intervention, or the main component of interventions, interventions were overall feasible and showed a significant improvement in cancer prevention and management.

Conclusions:
Social media tools have the potential to be effective in delivering interventions for cancer prevention and management. However, there was a dearth of studies with rigorous study methodologies to test social media effects on various cancer-related clinical outcomes.

Implications for Practice:
Social media use in cancer care will facilitate improved communication and support among patients, caregivers, and clinicians and, ultimately, improved patient care. Clinicians need to carefully harness social media to enhance patient care and clinical outcomes.
Expanding the Atlas of Functional Missense Variation for Human Genes
Authors: Weile Jochen , Sun Song , Cote Atina G. , Knapp Jennifer , Verby Marta , Mellor Joseph , Wu Yingzhou , Pons Carles , Wong Cassandra , Lieshout Natascha van , Yang Fan , Tasan Murat , Tan Guihong , Yang Shan , Fowler Douglas M. , Nussbaum Robert , Bloom Jesse D. , Vidal Marc , Hill David E , Aloy Patrick , Roth Frederick P. 
Published: July 2017

AbstractAlthough we now routinely sequence human genomes, we can confidently identify only a fraction of the sequence variants that have a functional impact. Here we developed a deep mutational scanning framework that produces exhaustive maps for human missense variants by combining random codon-mutagenesis and multiplexed functional variation assays with computational imputation and refinement. We applied this framework to four proteins corresponding to six human genes: UBE2I (encoding SUMO E2 conjugase), SUMO1 (small ubiquitin-like modifier), TPK1 (thiamin pyrophosphokinase), and CALM1/2/3 (three genes encoding the protein calmodulin). The resulting maps recapitulate known protein features, and confidently identify pathogenic variation. Assays potentially amenable to deep mutational scanning are already available for 57% of human disease genes, suggesting that DMS could ultimately map functional variation for all human disease genes.
Mapping movement, mood, motivation, and mentation in the subthalamic nucleus
Authors: Gourisankar Amritha , Eisenstein Sarah A. , Trapp Nicholas T. , Koller Jonathan M. , Campbell Meghan C. , Ushe Mwiza , Perlmutter Joel S. , Hershey Tamara , Black Kevin J. 
Published: July 2017

AbstractThe anatomical connections of the subthalamic nucleus (STN) have driven hypotheses about its functional anatomy, including the hypothesis that the precise anatomical location of STN deep brain stimulation (DBS) determines the variability of motor and non-motor responses across Parkinson disease (PD) patients. We previously tested that hypothesis using a three-dimensional (3D) statistical method to interpret the acute effects of unilateral DBS at each patient’s clinically optimized DBS settings and active contact. Here we report a similar analysis from a new study in which DBS parameters were standardized and DBS locations were chosen blind to clinical response. In 74 individuals with PD and STN DBS, STN contacts were selected near the dorsal and ventral border of the STN contralateral to the more affected side of the body. Participants were tested off PD medications in each of 3 conditions (ventral STN DBS, dorsal STN DBS and DBS off) for acute effects on mood, apathy, working memory, response inhibition and motor function. Voltage, frequency, and pulse width were standardized, and participants and raters were blind to condition. In a categorical analysis, both dorsal and ventral STN DBS improved mean motor function without affecting cognitive measures. Dorsal STN DBS induced greater improvement in rigidity than ventral STN DBS, whereas ventral STN DBS was more effective for improving anxiety and mood. In the 3D analysis, contact location was significant only for bradykinesia and resting tremor, with the greatest improvement occurring with DBS in dorsal STN and zona incerta. These results provide new, direct functional evidence for the anatomically-derived model of STN using the novel 3D analysis, in which motor function is most represented in dorsal STN. However, our data suggest that functional segregation between motor and non-motor areas of the STN is limited, since locations that induced improvements in motor function and mood overlapped substantially.
Modeling mesoscopic cortical dynamics using a mean-field model of conductance-based networks of adaptive exponential integrate-and-fire neurons
Authors: Zerlaut∗ Yann , Chemla Sandrine , Chavane Frederic , Destexhe∗ Alain 
Published: July 2017

AbstractVoltage-sensitive dye imaging (VSDi) has revealed fundamental properties of neocortical processing at macroscopic scales. Since for each pixel VSDi signals report the average membrane potential over hundreds of neurons, it seems natural to use a mean-field formalism to model such signals. Here, we present a mean-field model of networks of Adaptive Exponential (AdEx) integrate-and-fire neurons, with conductance-based synaptic interactions. We study here a network of regular-spiking (RS) excitatory neurons and fast-spiking (FS) inhibitory neurons. We use a Master Equation formalism, together with a semi-analytic approach to the transfer function of AdEx neurons to describe the average dynamics of the coupled populations. We compare the predictions of this mean-field model to simulated networks of RS-FS cells, first at the level of the spontaneous activity of the network, which is well predicted by the analytical description. Second, we investigate the response of the network to time-varying external input, and show that the mean-field model predicts the response time course of the population. Finally, to model VSDi signals, we consider a one-dimensional ring model made of interconnected RS-FS mean-field units. We found that this model can reproduce the spatio-temporal patterns seen in VSDi of awake monkey visual cortex as a response to local and transient visual stimuli. Conversely, we show that the model allows one to infer physiological parameters from the experimentally-recorded spatio-temporal patterns.
Reinforced Random Walker meets Spike Timing Dependent Plasticity
Authors: Soltanipour Mohammadreza , Seyed-allaei Hamed 
Published: July 2017

AbstractWe blended Reinforced Random Walker (RRW) and Spike Timing Dependent Plasticity (STDP) as a minimalistic model to study plasticity of neural network. The model includes walkers which randomly wander on a weighted network. A walker selects a link with a probability proportional to its weight. If the other side of the link is empty, the move succeeds and link’s weight is strengthened (Long Term Potentiation). If the other side is occupied, then the move fails and the weight of the link is weakened (Long Term Depression). Depending on the number of walkers, we observed two phases: ordered (a few strong loops) and disordered (all links are alike). We detected a phase transition from disorder to order depending on the number of walkers. At the transition point, where there was a balance between potentiation and depression, the system became scale-free and histogram of weights was a power law. This work demonstrate how dynamic of a complex adaptive system can lead to critical behavior in its structure via a STDP-like rule.
Quartet-based computations of internode certainty provide accurate and robust measures of phylogenetic incongruence
Authors: Zhou Xiaofan , Lutteropp Sarah , Czech Lucas , Stamatakis Alexandros , von Looz Moritz , Rokas Antonis 
Published: July 2017

AbstractIncongruence, or topological conflict, is prevalent in genome-scale data sets but relatively few measures have been developed to quantify it. Internode Certainty (IC) and related measures were recently introduced to explicitly quantify the level of incongruence of a given internode (or internal branch) among a set of phylogenetic trees and complement regular branch support statistics in assessing the confidence of the inferred phylogenetic relationships. Since most phylogenomic studies contain data partitions (e.g., genes) with missing taxa and IC scores stem from the frequencies of bipartitions (or splits) on a set of trees, the calculation of IC scores requires adjusting the frequencies of bipartitions from these partial gene trees. However, when the proportion of missing data is high, current approaches that adjust bipartition frequencies in partial gene trees tend to overestimate IC scores and alternative adjustment approaches differ substantially from each other in their scores. To overcome these issues, we developed three new measures for calculating internode certainty that are based on the frequencies of quartets, which naturally apply to both comprehensive and partial trees. Our comparison of these new quartet-based measures to previous bipartition-based measures on simulated data shows that: 1) on comprehensive trees, both types of measures yield highly similar IC scores; 2) on partial trees, quartet-based measures generate more accurate IC scores; and 3) quartet-based measures are more robust to the absence of phylogenetic signal and errors in the phylogenetic relationships to be assessed. Additionally, analysis of 15 empirical phylogenomic data sets using our quartet-based measures suggests that numerous relationships remain unresolved despite the availability of genome-scale data. Finally, we provide an efficient open-source implementation of these quartet-based measures in the programQuartetScores, which is freely available athttps://github.com/algomaus/QuartetScores.
Causal associations between risk factors and common diseases inferred from GWAS summary data
Authors: Zhu Zhihong , Zheng Zhili , Zhang Futao , Wu Yang , Trzaskowski Maciej , Maier Robert , Robinson Matthew R. , McGrath John J. , Visscher Peter M. , Wray Naomi R. , Yang Jian 
Published: July 2017

AbstractHealth risk factors such as body mass index (BMI), serum cholesterol and blood pressure are associated with many common diseases. It often remains unclear whether the risk factors are cause or consequence of disease, or whether the associations are the result of confounding. Genetic methods are useful to infer causality because genetic variants are present from birth and therefore unlikely to be confounded with environmental factors. We develop and apply a method (GSMR) that performs a multi-SNP Mendelian Randomization analysis using summary-level data from large genome-wide association studies (sample sizes of up to 405,072) to test the causal associations of BMI, waist-to-hip ratio, serum cholesterols, blood pressures, height and years of schooling (EduYears) with a range of common diseases. We identify a number of causal associations including a protective effect of LDL-cholesterol against type-2 diabetes (T2D) that might explain the side effects of statins on T2D, a protective effect of EduYears against Alzheimer’s disease, and bidirectional associations with opposite effects (e.g. higher BMI increases the risk of T2D but the effect T2D of BMI is negative). HDL-cholesterol has a significant risk effect on age-related macular degeneration, and the effect size remains significant accounting for the other risk factors. Our study develops powerful tools to integrate summary data from large studies to infer causality, and provides important candidates to be prioritized for further studies in medical research and for drug discovery.
Effects of population- and seed bank noise on neutral evolution and efficacy of natural selection
Authors: Heinrich Lukas , Müller Johannes , Tellier Aurélien , Živković Daniel 
Published: July 2017

AbstractPopulation genetics models typically consider a fixed population size and a unique selection coefficient. However, population dynamics inherently generate noise in numbers of individuals and selection acts on various components of the individuals’ fitness. In plant species with seed banks, the size of both the above- and below-ground compartments present noise depending on seed production and the state of the seed bank. We investigate if this noise has consequences on 1) the rate of genetic drift, and 2) the efficacy of selection. We consider four variants of two-allele Moran-type models defined by combinations of presence and absence of noise in above-ground and seed bank compartments. Time scale analysis and dimension reduction methods allow us to reduce the corresponding Fokker-Planck equation to a one-dimensional diffusive Moran model. We first show that if the above-ground noise classically affects the rate of genetic drift, below-ground noise reduces the diversity storage effect of the seed bank. Second, we consider that selection can act on four different components of the plant fitness: plant or seed death rate, seed production or seed germination. Our striking result is that the efficacy of selection for seed death rate or germination rate is reduced by seed bank noise, whereas selection occurring on plant death rate or seed production is not affected. We derive the expected site-frequency spectrum reflecting this heterogeneity in selection efficacy between genes underpinning different plant fitness components. Our results highlight the importance to consider the effect of ecological noise to predict the impact of seed banks on neutral and selective evolution.
Genome-wide association study of depression phenotypes in UK Biobank (n = 322,580) identifies the enrichment of variants in excitatory synaptic pathways
Authors: Howard David M. , Adams Mark J. , Shirali Masoud , Clarke Toni-Kim , Marioni Riccardo E. , Davies Gail , Coleman Jonathan R. I. , Alloza Clara , Shen Xueyi , Barbu Miruna C. , Wigmore Eleanor M. , Gibson Jude , Hagenaars Saskia P. , Lewis Cathryn M. , Smith Daniel J. , Sullivan Patrick F. , Haley Chris S. , Breen Gerome , Deary Ian J. , McIntosh Andrew M. 
Published: July 2017

AbstractDepression is a polygenic trait that causes extensive periods of disability and increases the risk of suicide, a leading cause of death in young people. Previous genetic studies have identified a number of common risk variants which have increased in number in line with increasing sample sizes. We conducted a genome-wide association study (GWAS) in the largest single population-based cohort to date, UK Biobank. This allowed us to estimate the effects of ≈ 8 million genetic variants in 320,000 people for three depression phenotypes: broad depression, probable major depressive disorder (MDD), and International Classification of Diseases (ICD, version 9 or 10)-coded MDD. Each phenotype was found to be significantly genetically correlated with the results from a previous independent study of clinically defined MDD. We identified 14 independent loci that were significantly associated (P < 5 × 10−8) with broad depression, two independent variants for probable MDD, and one independent variant for ICD-coded MDD. Gene-based analysis of our GWAS results with MAGMA revealed 46 regions significantly associated (P < 2.77 × 10−6) with broad depression, two significant regions for probable MDD and one significant region for ICD-coded MDD. Gene region-based analysis of our GWAS results with MAGMA revealed 59 regions significantly associated (P < 6.02 × 10−6) with broad depression, of which 27 were also detected by gene-based analysis. Variants for broad depression were enriched in pathways for excitatory neurotransmission, mechanosensory behavior, postsynapse, neuron spine and dendrite. This study provides a number of novel genetic risk variants that can be leveraged to elucidate the mechanisms of MDD and low mood.
Determining the specificity of Cascade binding, interference, and primed adaptationin vivoin theEscherichia colitype I-E CRISPR-Cas system
Authors: Cooper Lauren A. , Stringer Anne M. , Wade Joseph T. 
Published: July 2017

ABSTRACTIn CRISPR-Cas immunity systems, short CRISPR RNAs (crRNAs) are bound by CRISPR-associated (Cas) proteins, and these complexes target invading nucleic acid molecules for degradation in a process known as interference. In type I CRISPR-Cas systems, the Cas protein complex that binds DNA is known as Cascade. Association of Cascade with target DNA can also lead to acquisition of new immunity elements in a process known as primed adaptation. Here, we assess the specificity determinants for Cascade-DNA interaction, interference, and primed adaptationin vivo, for the type I-E system ofEscherichia coli. Remarkably, as few as 5 bp of crRNA-DNA are sufficient for association of Cascade with a DNA target. Consequently, a single crRNA promotes Cascade association with numerous off-target sites, and the endogenousE. colicrRNAs direct Cascade binding to >100 chromosomal sites. In contrast to the low specificity of Cascade-DNA interactions, >18 bp are required for both interference and primed adaptation. Hence, Cascade binding to sub-optimal, off-target sites is inert. Our data support a model in which initial Cascade association with DNA targets requires only limited sequence complementarity at the crRNA 5□ end, whereas recruitment and/or activation of the Cas3 nuclease, a prerequisite for interference and primed adaptation, requires extensive base-pairing.IMPORTANCEMany bacterial and archaeal species encode CRISPR-Cas immunity systems that protect against invasion by foreign DNA. In theEscherichia coliCRISPR-Cas system, a protein complex, Cascade, binds 61 nt CRISPR RNAs (crRNAs). The Cascade complex is directed to invading DNA molecules through base-pairing between the crRNA and target DNA. This leads to recruitment of the Cas3 nuclease that destroys the invading DNA molecule and promotes acquisition of new immunity elements. We make the firstin vivomeasurements of Cascade binding to DNA targets. Thus, we show that Cascade binding to DNA is highly promiscuous; endogenousE. colicrRNAs can direct Cascade binding to >100 chromosomal locations. By contrast, we show that target degradation and acquisition of new immunity elements requires highly specific association of Cascade with DNA, limiting CRISPR-Cas function to the appropriate targets.