bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brief Report: Soluble CD163 in CMV-Infected and CMV-Uninfected Subjects on Virologically Suppressive Antiretroviral Therapy in the ICONA Cohort
Authors: Vita Serena , Lichtner Miriam , Marchetti Giulia , Mascia Claudia , Merlini Esther , Cicconi Paola , Vullo Vincenzo , Viale Pierluigi , Costantini Andrea , D'Arminio Monforte Antonella ,   for ICONA Foundation Study Group
Published: November 2016

Aims:
To contribute to the understanding of the role played by cytomegalovirus (CMV) in sustaining monocyte/macrophage-mediated immune activation in antiretroviral therapy treated HIV-infected subjects.

Design and Methods:
We selected 23 CMV-uninfected and 46 CMV-infected HIV+ subjects, matched for age, CD4 nadir, HIV infection duration, and viral hepatitis serostatus. All subjects were on successful antiretroviral therapy since at least 1 year. A group of 16 healthy donors with similar age and sex was also included. Plasma levels of tumor necrosis factor–alpha, interleukin-6, sCD163, sCD14, and CMV immunoglobulin G levels were measured in duplicate with human enzyme-linked immunosorbent assay kits.

Results:
We found significantly higher sCD163 plasma levels in HIV+CMV+ compared with HIV+CMV− subjects and healthy donors. This augmentation was confirmed also when subjects positive for hepatitis C virus–Ab were excluded from analysis. Interestingly, a correlation between anti-CMV immunoglobulin G levels and sCD163, tumor necrosis factor–alpha, interleukin-6, and sCD14 in HIV+CMV+ subjects was found.

Conclusions:
CMV coinfection could be a major driver of monocyte/macrophage activation in virally suppressed HIV+ individuals and might explain the increased risk of non-AIDS morbidity/mortality in HIV/CMV-coinfected subjects.
Managing chronic kidney disease in the older adults living with HIV
Authors: Post Frank A. 
Published: November 2016

Purpose of review
HIV replication and immunodeficiency are important risk factors for chronic kidney disease (CKD). Widespread use of antiretrovirals that may affect kidney function underscores the need for monitoring kidney function, allowing early detection of drug-induced kidney injury and identification of patients who may benefit from antiretroviral therapy switches.

Recent findings
Several cohorts have reported an increased incidence of CKD with tenofovir [tenofovir disoproxil fumarate (TDF)], atazanavir, and lopinavir, and CKD risk scores have been developed to identify those most at risk of kidney disease progression while receiving these agents. Recent data suggest that TDF discontinuation and substitution of atazanavir or lopinavir with darunavir may stabilize or improve renal function. Tenofovir alafenamide (TAF) is a new tenofovir formulation with minimal effect on renal tubular function. Patients with preserved or mild–moderately impaired renal function who switched from TDF to TAF-containing regimens experienced rapid and sustained improvement in proteinuria and stable renal function, suggesting that TAF will be the preferred tenofovir formulation for patients with CKD and those at increased risk of developing CKD.

Summary
Suppression of HIV replication and antiretroviral switches away from TDF and atazanavir are important measures to maintain kidney function and reduce CKD risk in older adults living with HIV.
Community-acquired bacterial meningitis
Authors: Costerus Joost M. , Brouwer Matthijs C. , Bijlsma Merijn W. , van de Beek Diederik 
Published: November 2016

Purpose of review
Bacterial meningitis is a medical emergency and is associated with a high disease burden. We reviewed recent progress in the management of patients with community-acquired bacterial meningitis.

Recent findings
The worldwide burden of disease of bacterial meningitis remains high, despite the decreasing incidence following introduction of routine vaccination campaigns. Delay in diagnosis and treatment remain major concerns in the management of acute bacterial meningitis. European Society of Clinical Microbiology and Infectious Diseases guidelines strive for a door-to-antibiotic-time less than 1 h. Polymerase chain reaction (PCR) has emerged as an important diagnostic tool to identify the causative organism. Point-of-care tests using fast multiplex PCR have been developed, but additional value has not been proven. Although anecdotal observations advocate pressure-based management, a randomized controlled trial will need to be performed first to determine efficacy and safety of such an aggressive treatment approach. Adjunctive dexamethasone remains the only adjunctive therapy with proven efficacy.

Summary
The incidence of bacterial meningitis has been decreasing after the implementation of effective vaccines. Treatment should be administered as soon as possible and time to treatment should not exceed 1 h.
Speed in Clinical Magnetic Resonance
Authors: Runge Val M. , Richter Johannes K. , Heverhagen Johannes T. 
Published: November 2016

Abstract
The relevant clinical accelerated magnetic resonance techniques that are available currently for routine patient examinations are reviewed, presenting and discussing the benefits therein when compared with more conventional scans. The focus is on clinical use and practicality, with the review divided into 3 sections. Improvements in 3-dimensional acquisition are first discussed, specifically controlled aliasing in parallel imaging results in higher acceleration, related radial techniques, and CAIPI-Dixon-TWIST-VIBE. Simultaneous multislice imaging is then reviewed, focusing on current implementation for 2-dimensional imaging, including both echo-planar and fast spin echo techniques. The final topic is that of sparse reconstruction (data sparsity), discussing the principles therein, challenges, and current applications. Guidance in terms of clinical use for accelerated techniques is provided, focusing on enabling faster and improved clinical scan results.
Alcohol Use Disorder as a Possible Predictor of Electroconvulsive Therapy Response
Authors: Aksay Suna Su , Hambsch Melanie , Janke Christoph , Bumb Jan Malte , Kranaster Laura , Sartorius Alexander 
Published: November 2016

Introduction
Two rapidly acting antidepressive treatment forms, namely, electroconvulsive therapy (ECT) and ketamine, possibly share a common mechanism of action primarily involving alterations of neurotransmission (glutamate and γ-aminobutyric acid levels). Because patients receiving ketamine and with a coexistent family history of an alcohol use disorder (AUD) seem to benefit from consistent and longer lasting antidepressive effects, we hypothesized better treatment response in ECT patients with an own history or a family history of an AUD.

Method
One hundred forty-one psychiatric inpatients with a major depressive episode, who were treated with ECT, were enrolled into this retrospective study. Age, sex, family or personal history of alcohol or benzodiazepine use disorder, ECT response data, and ECT treatment-related data were collected and analyzed with ordinal logistic regression and Fisher exact tests.

Results
Twenty-one percent of all patients had their own history of an AUD, 11% had their own history of a benzodiazepine use disorder, and 11% reported on a positive family history of alcohol or benzodiazepine use disorder. The logistic regression analyses revealed that only patient's own history of an AUD predicts a better ECT response (P = 0.031; odds ratio, 2.1; Fisher exact test, P = 0.006).

Conclusions
Within the limitations of a retrospective study, a history of an AUD seems to be a positive predictor for an ECT response in patients experiencing a major depressive episode, which has not been found in 2 earlier studies. Findings are in line with neurobiological hypotheses of excitatory/inhibitory neurotransmitter changes with ketamine and ECT.
A potential mechanism for the first-person inner sensation of memory provides evidence for a relationship between learning and LTP induction
Authors: Vadakkan Kunjumon I. 
Published: November 2016

AbstractLarge number of correlations have been observed between behavioral markers of memory and long-term potentiation (LTP). However, there are different non-correlated findings that need explanations. Examples include a) a delay of at least thirty seconds for LTP induction after stimulation that does not match with milliseconds of time required for associative learning, and b) the deficiency of the LTP mechanism for providing a structure-function mechanism for working memory. By viewing memories as first-person inner sensations, a derived mechanism can explain various features of LTP and its mismatched findings with that of normal learning.
Resting state functional coupling between the ascending synchronising system, limbic system and the default mode network via theta oscillations
Authors: Raniga Parnesh , Paton Bryan , Egan Gary F. 
Published: November 2016

AbstractIn order to better understand dysfunction in dementia and psychiatric illnesses, the underlying neuronal systems that give rise to normal memory and cognitive processes need to be better understood. Based on electrophysiological recordings in animals, theta oscillations have been proposed as an intrinsic mechanism for the orchestration of memory functions, especially episodic and autobiographical memory. Theta oscillations are controlled by the ascending synchronising system, a set of nucleui in the pontine tegmentum and basal forebrain. At a network level, the default mode network has been shown to be responsible for episodic and autobiographical.Using resting state fMRI data, we show using an ICA approach, seed based connectivity and dynamic causal modelling that the ascending synchronising system is coupled to the medial temporal lobe nodes including the hippocampus and parahippocampal gyrus and with the default mode network. Our results provide thus support the role of theta oscillations in memory function and coordination at a network level.HighlightsResting state functional coupling between the DMN, MTL and ascending synchronising system.Theta oscillations may be the basis of this coupling given the role of these structures in control of theta.Theta oscillations have been implicated in memory, cognition and predictive coding.DMN, MTL and ASS are implicated in Alzheimer’s disease.AbbreviationsMRIMagnetic resonance imagingfMRIfunctional magnetic resonance imagingrs-fmriresting state functional magnetic resonance imagingPnOPontine nucleus oralisSuMSupra-mamillary nucleus.MSMedial septumDBDiagonal band of Broca.VTAventral tegmental areaPCCPosterior cingulate cortexHCHippocampusARASAscending reticular activating systemASSAscending synchronising systemDMNDefault Mode NetworkaMPFCAnterior Medial Prefrontal CortexpIPLPosterior inferior parietal lobuleNBMNucleus Basalis MynertDCMDynamic causal modellingPHGParahippocampal Gyrus
Ribo-attenuators: novel elements for reliable and modular riboswitch engineering
Authors: Folliard Thomas , Mertins Barbara , Prescott Thomas P , Steel Harrison , Newport Thomas , Jones Christopher W , Bayer Travis , Armitage Judith P , Papachristodoulou Antonis , Rothschild Lynn J 
Published: November 2016

AbstractRiboswitches are structural genetic regulatory elements that directly couple the sensing of small molecules to gene expression. They have considerable potential for applications throughout synthetic biology and bio-manufacturing as they are able to sense a wide range of small molecules and regulate gene expression in response. Despite over a decade of research they have yet to reach this considerable potential as they cannot yet be treated as modular components. This is due to several limitations including sensitivity to changes in genetic context, low tunability, and variability in performance. To overcome the associated difficulties with riboswitches, we have designed and introduced a novel genetic element called a Ribo-attenuator in Bacteria. This genetic element allows for predictable tuning, insulation from contextual changes, and a reduction in expression variation. Ribo-attenuators allow riboswitches to be treated as truly modular and tunable components, and thus increases their reliability for a wide range of applications.
Anchored Phylogenomics of Angiosperms I: Assessing the Robustness of Phylogenetic Estimates
Authors: Buddenhagen Chris , Lemmon Alan R. , Lemmon Emily Moriartya , Bruhl Jeremy , Cappa Jennifer , Clement Wendy L. , Donoghue Michael J. , Edwards Erika J. , Hipp Andrew L. , Kortyna Michelle , Mitchell Nora , Moore Abigail , Prychid Christina J. , Segovia-Salcedo Maria C. , Simmons Mark P. , Soltis Pamela S. , Wanke Stefan , Mast Austin 
Published: November 2016

ABSTRACTAn important goal of the angiosperm systematics community has been to develop a shared approach to molecular data collection, such that phylogenomic data sets from different focal clades can be combined for meta-studies across the entire group. Although significant progress has been made through efforts such as DNA barcoding, transcriptome sequencing, and whole-plastid sequencing, the community current lacks a cost efficient methodology for collecting nuclear phylogenomic data across all angiosperms. Here, we leverage genomic resources from 43 angiosperm species to develop enrichment probes useful for collecting ~500 loci from non-model taxa across the diversity of angiosperms. By taking an anchored phylogenomics approach, in which probes are designed to represent sequence diversity across the group, we are able to efficiently target loci with sufficient phylogenetic signal to resolve deep, intermediate, and shallow angiosperm relationships. After demonstrating the utility of this resource, we present a method that generates a heat map for each node on a phylogeny that reveals the sensitivity of support for the node across analysis conditions, as well as different locus, site, and taxon schemes. Focusing on the effect of locus and site sampling, we use this approach to statistically evaluate relative support for the alternative relationships among eudicots, monocots, and magnoliids. Although the results from supermatrix and coalescent analyses are largely consistent across the tree, we find support for this deep relationship to be more sensitive to the particular choice of sites and loci when a supermatrix approach as employed. Averaged across analysis approaches and data subsampling schemes, our data support a eudicot-monocot sister relationship, which is supported by a number of recent angiosperm studies.
Rotamer libraries for the high-resolution design of β-amino acid foldamers
Authors: Watkins Andrew M. , Craven Timothy W. , Renfrew P. Douglas , Arora Paramjit S. , Bonneau Richard 
Published: November 2016

Abstractβ-amino acids offer attractive opportunities to develop biologically active peptidomimetics, either employed alone or in conjunction with natural α-amino acids. Owing to their potential for unique conformational preferences that deviate considerably from α-peptide geometries, β-amino acids greatly expand the possible chemistries and physical properties available to polyamide foldamers. Completein silicosupport for designing new molecules incorporating nonnatural amino acids typically requires representing their side chain conformations as sets of discrete rotamers for model refinement and sequence optimization. Such rotamer libraries are key components of several state of the art design frameworks. Here we report the development, incorporation in to the Rosetta macromolecular modeling suite, and validation of rotamer libraries for β3-amino acids.
Asymmetrical representation of the upper and lower visual fields in oculomotor maps
Authors: Wang Zhiguo , Wang Benchi , Finkbeiner Matthew 
Published: November 2016

AbstractThe striate area devoted to the lower visual field (LVF) is larger than that devoted to the upper visual field (UVF). A similar anatomical asymmetry also exists in the LGN. Here we take advantage of two experimental tasks that are known to modulate the direction and amplitude of saccades to demonstrate a visual field asymmetry in oculomotor maps. Participants made visually guided saccades. In Experiment 1, the saccade target was accompanied by a visual distractor. The distractor’s presence modulated the direction of saccades, and this effect was much stronger for LVF targets. In Experiment 2, the temporal gap between the offset of the fixation stimulus and the onset of the saccade target was manipulated. This manipulation modulated the amplitude of saccades and this modulation was stronger for saccades towards UVF targets. Taken together, these results suggest that the representation of both meridians and eccentricities in the LVF is compressed in oculomotor maps.
A Deep Boosting Based Approach for Capturing the Sequence Binding Preferences of RNA-Binding Proteins from High-Throughput CLIP-Seq Data
Authors: Li Shuya , Dong Fanghong , Wu Yuexin , Zhang Sai , Zhang Chen , Liu Xiao , Jiang Tao , Zeng Jianyang 
Published: November 2016

AbstractCharacterizing the binding behaviors of RNA-binding proteins (RBPs) is important for understanding their functional roles in gene expression regulation. However, current high-throughput experimental methods for identifying RBP targets, such as CLIP-seq and RNAcompete, usually suffer from the false positive and false negative issues. Here, we develop a deep boosting based machine learning approach, called DeBooster, to accurately model the binding sequence preferences and identify the corresponding binding targets of RBPs from CLIP-seq data. Comprehensive validation tests have shown that DeBooster can outperform other state-of-the-art approaches in predicting RBP targets and recover false negatives that are common in current CLIP-seq data. In addition, we have demonstrated several new potential applications of DeBooster in understanding the regulatory functions of RBPs, including the binding effects of the RNA helicase MOV10 on mRNA degradation, the influence of different binding behaviors of the ADAR proteins on RNA editing, as well as the antagonizing effect of RBP binding on miRNA repression. Moreover, DeBooster may provide an effective index to investigate the effect of pathogenic mutations in RBP binding sites, especially those related to splicing events. We expect that DeBooster will be widely applied to analyze large-scale CLIP-seq experimental data and can provide a practically useful tool for novel biological discoveries in understanding the regulatory mechanisms of RBPs.
Selection on the FADS region in Europeans
Authors: Buckley Matthew T. , Racimo Fernando , Allentoft Morten E. , Jensen Majken K. , Jonsson Anna , Huang Hongyan , Hormozdiari Farhad , Sikora Martin , Marnetto Davide , Eskin Eleazar , Jørgensen Marit E. , Grarup Niels , Pedersen Oluf , Hansen Torben , Kraft Peter , Willerslev Eske , Nielsen Rasmus 
Published: November 2016

Abstract:FADSgenes encode fatty acid desaturases that are important for the conversion of short chain polyunsaturated fatty acids (PUFAs) to long chain fatty acids. Prior studies indicate that theFADSgenes have been subjected to strong positive selection in Africa, South Asia, Greenland, and Europe. By comparingFADSsequencing data from present-day and Bronze Age (5-3k years ago) Europeans, we identify possible targets of selection in the European population, which suggest that selection has targeted different alleles in theFADSgenes in Europe than it has in South Asia or Greenland. The alleles showing the strongest changes in allele frequency since the Bronze Age show associations with expression changes and multiple lipid-related phenotypes. Furthermore, the selected alleles are associated with a decrease in linoleic acid and an increase in arachidonic and eicosapentaenoic acids among Europeans; this is an opposite effect of that observed for selected alleles in Inuit from Greenland. We show that multiple SNPs in the region affect expression levels and PUFA synthesis. Additionally, we find evidence for a gene-environment interaction influencing low-density lipoprotein (LDL) levels between alleles affecting PUFA synthesis and PUFA dietary intake: carriers of the selected, derived allele have diminished increases in LDL cholesterol with a higher intake of PUFAs. We hypothesize that the selective patterns observed in Europeans were driven by a change in dietary composition of fatty acids following the transition to agriculture, resulting in a lower intake of arachidonic acid and eicosapentaenoic acid, but a higher intake of linoleic acid and α-linolenic acid.
Phage mobility is a core determinant of phage-bacteria coexistence in biofilms
Authors: Simmons Matthew , Drescher Knut , Nadell Carey D. , Bucci Vanni 
Published: November 2016

AbstractMany bacteria are adapted for attaching to surfaces and for building complex communities, termed biofilms. The biofilm mode of life is predominant in bacterial ecology. So, too, is exposure of bacteria to ubiquitous viral pathogens, termed bacteriophages. Although biofilmphage encounters are likely to be very common in nature, little is known about how phages might interact with biofilm-dwelling bacteria. It is also unclear how the ecological dynamics of phages and their hosts depend on the biological and physical properties of the biofilm environment. To make headway in this area, here we develop the first biofilm simulation framework that captures key mechanistic features of biofilm growth and phage infection. Using these simulations, we find that the equilibrium state of interaction between biofilms and phages is governed largely by nutrient availability to biofilms, infection likelihood per host encounter, and the ability of phages to diffuse through biofilm populations. Interactions between the biofilm matrix and phage particles are thus likely to be of fundamental importance, controlling the extent to which bacteria and phages can coexist in natural contexts. Our results open avenues to new questions of host-parasite coevolution and horizontal gene transfer in spatially structured biofilm contexts.
Novel computational method for predicting polytherapy switching strategies to overcome tumor heterogeneity and evolution
Authors: Jonsson Vanessa D. , Blakely Collin M. , Lin Luping , Asthana Saurabh , Olivas Victor , Gubens Matthew A. , Matni Nikolai , Bastian Boris C. , Taylor Barry S. , Doyle John C. , Bivona Trever G. 
Published: November 2016

1AbstractThe success of targeted cancer therapy is limited by drug resistance that can result from tumor genetic heterogeneity. The current approach to address resistance typically involves initiating a new treatment after clinical/radiographic disease progression, ultimately resulting in futility in most patients. Towards a potential alternative solution, we developed a novel computational framework that uses human cancer profiling data to systematically identify dynamic, pre-emptive, and sometimes non-intuitive treatment strategies that can better control tumors in real-time. By studying lung adenocarcinoma clinical specimens and preclinical models, our computational analyses revealed that the best anti-cancer strategies addressed existing resistant subpopulations as they emerged dynamically during treatment. In some cases, the best computed treatment strategy used unconventional therapy switching while the bulk tumor was responding, a prediction we confirmed in vitro. The new framework presented here could guide the principled implementation of dynamic molecular monitoring and treatment strategies to improve cancer control.