bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brief Report: Changes in Plasma RANKL-Osteoprotegerin in a Prospective, Randomized Clinical Trial of Initial Antiviral Therapy: A5260s
Authors: Kelesidis Theodoros , Moser Carlee B. , Johnston Elizabeth , Stein James H. , Dube Michael P. , Yang Otto O. , McComsey Grace A. , Currier Judith S. , Brown Todd T. 
Published: March 2018

Background:
The contributions of the receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) axis to cardiovascular and bone disease in treated HIV-1 infection are not well defined.

Setting:
Prospective, observational, longitudinal study.

Methods:
In a subset analysis of a prospective randomized clinical trial, 234 HIV-1–infected antiretroviral therapy–naive participants received tenofovir–emtricitabine plus either atazanavir/ritonavir, darunavir/ritonavir, or raltegravir and achieved plasma HIV-1 RNA <50 copies per milliliter by week 24 and thereafter. Associations between plasma RANKL, OPG, or RANKL/OPG ratio levels with total, hip, and spine bone mineral density (BMD) loss or progression of carotid artery intima-media thickness were assessed longitudinally over 96 weeks.

Results:
Over 96 weeks, all treatment groups had similar and sustained declines in plasma RANKL, increases in plasma OPG, and subsequently, decreases in the RANKL/OPG ratio. There were no associations between plasma RANKL or RANKL/OPG ratio levels with total, hip, and spine BMD loss or progression of carotid artery intima-media thickness; however, plasma OPG in successfully treated HIV-infected patients (week 48 and 96) was associated with spine BMD loss.

Conclusions:
In virologically suppressed HIV-infected patients, the evolution of bone disease could be linked to plasma OPG levels; however, the role of plasma levels of RANKL and RANKL/OPG ratio in the prediction of morbidity in treated HIV-1 infection may be limited.
Antipsychotic-Induced Pisa Syndrome: A 2-Year Follow-up Study
Authors: Lee Yen-Feng 
Published: March 2018

Objectives
Pisa syndrome is characterized by lateral trunk flexion. It is an uncommon adverse drug reaction in patients on antipsychotic medication. Although Pisa syndrome has been reported in patients on antipsychotic treatment, previous studies have not discussed the prognosis of patients with Pisa syndrome. We studied psychiatric patients with Pisa syndrome following antipsychotic treatment for a 2-year period.

Methods
From January 2012 to December 2014, 13 inpatients with Pisa syndrome following antipsychotic treatment were identified at our institution, from a prospectively collected database. These patients were studied for a 2-year period.

Results
The prevalence rate of Pisa syndrome during neuroleptic treatment was 0.45% in men and 0.37% in women, with a collective prevalence rate of 0.42%. The mean age of patients with Pisa syndrome was 47 years. Eight (61.5%) of the cases had a position with a tilt toward the right side. In 5 (38.5%) of the cases, a tilt toward the left side was observed. The average Cobb angle of the trunk was 17.3 (SD, 4.0) degrees. On presentation with Pisa syndrome within 3 months of medication modification, the pattern of trunk dystonia had a significantly shorter duration (P = .024) compared with that seen in the tardive-onset group.

Conclusions
Pisa syndrome is an uncommon adverse event that can also be chronic or recurrent, especially in those with tardive onset. We should be aware of the risks in patients with the following predisposing factors: old age, chronic psychosis, long-term antipsychotic use, advanced drug-induced parkinsonism, and combined pharmacologic treatment.
Does Continuous Video-EEG in Patients With Altered Consciousness Improve Patient Outcome? Current Evidence and Randomized Controlled Trial Design
Authors: Rossetti Andrea O. , Schindler Kaspar , Alvarez Vincent , Sutter Raoul , Novy Jan , Oddo Mauro , Warpelin-Decrausaz Loane , Rüegg Stephan 
Published: March 2018

Summary:
Continuous video-EEG is recommended for patients with altered consciousness; as compared to routine EEG (lasting <30 minutes), it improves seizure detection, but is time- and resource-consuming. Although North American centers increasingly implement continuous video-EEG, most other (including European) hospitals have insufficient resources. Only one study suggested that continuous video-EEG could improve outcome in adults, and recent assessments challenge this view. This article reviews current evidence on the added value for continuous video-EEG in clinical terms and describes a design for a prospective study.
In a multicenter randomized clinical trial (NCT03129438), adults with a Glasgow Coma Scale ≤11 will be randomized 1:1 to continuous video-EEG (cEEG) for 30 to 48 hours or 2 routine EEG (rEEG), assessed through standardized American Clinical Neurophysiology Society (ACNS) guidelines. The primary outcome will be mortality at 6 months, assessed blindly. Secondary outcomes will explore functional status at 4 weeks and 6 months, intensive care unit (ICU) length of stay, infection rates, and hospitalization costs. Using a 2-sided approach with power of 0.8 and a error of 0.05, 2 × 174 patients are needed to detect an absolute survival difference of 14%, suggested by the single available study on the topic.
This study should help clarifying whether cEEG has a significant impact on outcome and define its cost effectiveness. If the trial will result positive, it will encourage broader implementation of cEEG with consecutive substantial impact on health care and resource allocations. If not, it may offer a rationale to design a larger trial, and – at least for smaller centers – to avoid widespread implementation of cEEG, rationalizing personnel and device costs.
Resource-driven changes to host population stability alter the evolution of virulence and transmission
Authors: Hite Jessica L. , Cressler Clayton E. 
Published: March 2018

What drives the evolution of parasite life-history traits? Recent studies suggest that linking within- and between-host processes can provide key insight into both disease dynamics and parasite evolution. Still, it remains difficult to understand how to pinpoint the critical factors connecting these cross-scale feedbacks, particularly under non-equilibrium conditions; many natural host populations inherently fluctuate and parasites themselves can strongly alter the stability of host populations. Here, we develop a general model framework that mechanistically links resources to parasite evolution across a gradient of stable and unstable conditions. First, we dynamically link resources and between-host processes (host density, stability, transmission) to virulence evolution, using a ‘non-nested’ model. Then, we consider a ‘nested’ model where population-level processes (transmission and virulence) depend on resource-driven changes to individual-level (within-host) processes (energetics, immune function, parasite production). Contrary to ‘non-nested’ model predictions, the ‘nested’ model reveals complex effects of host population dynamics on parasite evolution, including regions of evolutionary bistability; evolution can push parasites towards strongly or weakly stabilizing strategies. This bistability results from dynamic feedbacks between resource-driven changes to host density, host immune function and parasite production. Together, these results highlight how cross-scale feedbacks can provide key insights into the structuring role of parasites and parasite evolution.This article is part of the theme issue ‘Anthropogenic resource subsidies and host–parasite dynamics in wildlife’.
Human–nature interactions and the consequences and drivers of provisioning wildlife
Authors: Cox Daniel T. C. , Gaston Kevin J. 
Published: March 2018

Many human populations are undergoing an extinction of experience, with a progressive decline in interactions with nature. This is a consequence both of a loss of opportunity for, and orientation towards, such experiences. The trend is of concern in part because interactions with nature can be good for human health and wellbeing. One potential means of redressing these losses is through the intentional provision of resources to increase wildlife populations in close proximity to people, thereby increasing the potential for positive human–nature experiences, and thence the array of benefits that can result. In this paper, we review the evidence that these resource subsidies have such a cascade of effects. In some Westernized countries, the scale of provision is extraordinarily high, and doubtless leads to both positive and negative impacts for wildlife. In turn, these impacts often lead to more frequent, reliable and closer human–nature interactions, with a greater variety of species. The consequences for human wellbeing remain poorly understood, although benefits documented in the context of human–nature interactions more broadly seem likely to apply. There are also some important feedback loops that need to be better characterized if resource provisioning is to contribute effectively towards averting the extinction of experience.This article is part of the theme issue ‘Anthropogenic resource subsidies and host–parasite dynamics in wildlife’.
Comparative Transcriptomic and Metabolomic Analyses in Response to Cold in Tartary Buckwheat (Fagopyrum tataricum)
Authors: Jeon Jin , Kim Jae Kwang , Wu Qi , Park Sang Un 
Published: March 2018

AbstractPlants recognize multiple environmental signals that lead to substantial changes in the regulation of primary and secondary metabolism in order to adapt to environmental stresses. In this study, we investigate the effects of cold on the metabolome and transcriptome of tartary buckwheat, focusing on the phenylpropanoid biosynthetic pathway. Using RNA-sequencing analysis of the cold-regulated transcriptome of buckwheat, we identified several phenylpropanoid biosynthetic transcripts that accumulated in response to cold. To confirm the transcriptome data, we analyzed the expression of the phenylpropanoid biosynthetic transcripts in cold-treated buckwheat and showed that all the phenylpropanoid biosynthetic transcripts were upregulated in coldtreated buckwheat seedlings with the exception of FtDFR. From the metabolic profiling based on the GC-TOF-MS analysis, we show that most of the sugars and their derivatives significantly increase in response to cold, while some of amino acids and their derivatives decrease in cold-treated plants. Some organic acids derived from the tricarboxylic acid (TCA) cycle increased in the cold-treated plants compared with in the plants grown at 25°C. In particular, the contents of anthocyanins and proanthocyanidins were significantly increased by cold treatment. In summary, these results indicate that the metabolome and transcriptome of tartary buckwheat are extensively affected by cold stresses.HighlightUsing the RNA-sequencing data and the metabolic profiling analysis, we identified the changes that occur in the transcriptome and metabolome of tartary buckwheat in response to cold, focusing on the flavonoid biosynthetic pathway.AbbreviationsANRanthocyanidin reductaseANSAnthocyanin synthaseC4Hcinnamate 4-hydroxylaseCHIchalcone isomeraseCHSchalcone synthase4CL4-coumarate:CoA ligaseDFRdihydroflavonol reductaseDPPH2,2-diphenyl-1-picrylhydrazylF3Hflavanone 3-hydroxylaseF3’Hflavonoid 3’-hydroxylaseFLSflavonol synthaseGC-TOFMSgas chromatography-time of flight mass spectrometry3GTflavonoid 3-O-glucosyltransferaseHPLChigh-performance l iquid chromatographyLARleucoanthocyanidinPAproanthocyanidinPALphenylalanine ammonia-lyaseRT3-O-rhamnosyltransferaseTCAtricarboxylic acid.
Capturing diverse microbial sequence with comprehensive and scalable probe design
Authors: Metsky Hayden C. , Siddle Katherine J. , Gladden-Young Adrianne , Qu James , Yang David K. , Brehio Patrick , Goldfarb Andrew , Piantadosi Anne , Wohl Shirlee , Carter Amber , Lin Aaron E. , Barnes Kayla G. , Tully Damien C. , Corleis Björn , Hennigan Scott , Barbosa-Lima Giselle , Vieira Yasmine R. , Paul Lauren M. , Tan Amanda L. , Garcia Kimberly F. , Parham Leda A. , Odia Ikponmwonsa , Eromon Philomena , Folarin Onikepe A. , Goba Augustine ,   Viral Hemorrhagic Fever Consortium, Simon-Lorière Etienne , Hensley Lisa , Balmaseda Angel , Harris Eva , Kwon Douglas , Allen Todd M. , Runstadler Jonathan A. , Smole Sandra , Bozza Fernando A. , Souza Thiago M. L. , Isern Sharon , Michael Scott F. , Lorenzana Ivette , Gehrke Lee , Bosch Irene , Ebel Gregory , Grant Donald , Happi Christian , Park Daniel J. , Gnirke Andreas , Sabeti Pardis C. , Matranga Christian B. 
Published: March 2018

AbstractMetagenomic sequencing has the potential to transform microbial detection and characterization, but new tools are needed to improve its sensitivity. We developed CATCH (Compact Aggregation of Targets for Comprehensive Hybridization), a computational method to enhance nucleic acid capture for enrichment of diverse microbial taxa. CATCH designs compact probe sets that achieve full coverage of known sequence diversity and that scale well with this diversity. To illustrate applications of CATCH, we focused on capturing viral genomes. We designed, synthesized, and validated multiple probe sets, including one that targets whole genomes of the 356 viral species known to infect humans. Capture with these probe sets enriched unique viral content on average 18× and allowed us to assemble genomes that we could not otherwise recover, while accurately preserving within-sample diversity. We used this approach to recover genomes from the 2018 Lassa fever outbreak in Nigeria and to improve detection of viral infections in samples with unknown content. Together, this work demonstrates a path toward more sensitive, cost-effective metagenomic sequencing.
Dysregulation of the engulfment pathway in the gut fuels Inflammatory Bowel Disease
Authors: Suarez Katherine , Lim Eileen , Singh Sujay , Pereira Matheus , Joosen Linda Petronella , Ibeawuchi Stella-Rita , Dunkel Ying , Mittal Yash , Ho Samuel B. , Chattopadhyay Ranajoy , Guma Monica , Boland Brigid S. , Dulai Parambir S. , Sandborn William J. , Ghosh Pradipta , Das Soumita 
Published: March 2018

AbstractBACKGROUND & AIMSLuminal dysbiosis is ubiquitous in inflammatory bowel disease (IBD), but how the microbes trigger pro-inflammatory cascades in the epithelial and phagocytic cells remains unknown. Here we investigated the role of the microbial sensor ELMO1 (Engulfment and Cell Motility Protein-1) in sensing and responding to IBD-associated microbes in the gut epithelium and in macrophages.METHODSA stem cell-based technique is used to grow enteroids from WT and ELMO1−/−mice and from colonic biopsies of patients with IBD and subsequently differentiate them into enteroid-derived monolayers (EDMs) that mimic the gut epithelium/Gut in a dish. EDMs infected with IBD-associated invasiveE. coli-LF82 were analyzed for bacterial internalization, cytokine production and monocyte-recruitment when co-cultured with monocytes.RESULTSExpression of ELMO1 is elevated in the colonic epithelium and in the inflammatory infiltrates within the lamina propria in IBD, higher expression correlated with elevated expression of pro-inflammatory cytokines, MCP-1 and TNF-α. ELMO1-/-murine EDMs displayed a significant reduction of bacterial internalization through epithelial tight junctions and in MCP-1 production compared to WT mice. MCP-1 that is released from the epithelium recruited monocytes. Once recruited, macrophages required ELMO1 to engulf the bacteria and propagate a robust pro-inflammatory cytokine storm (TNF-α).CONCLUSIONSELMO1 couples microbial-sensing to inflammation in both phagocytic and non-phagocytic host cells; it is required for the production of MCP-1 in the epithelium and TNF-α in macrophages. Findings raise the possibility that upregulation of epithelial ELMO1 and the epithelial ELMO1→MCP-1 axis may serve as an early biomarker and therapeutic target, respectively, in IBD and other disorders of inflammation.
Dynamic integration of conceptual information during learning
Authors: Inhoff Marika C. , Libby Laura A. , Noguchi Takao , Love Bradley C. , Ranganath Charan 
Published: March 2018

AbstractThe development and application of concepts is a critical component of cognition. Although concepts can be formed on the basis of simple perceptual or semantic features, conceptual representations can also capitalize on similarities across feature relationships. By representing these types of higher-order relationships, concepts can simplify the learning problem and facilitate decisions. Despite this, little is known about the neural mechanisms that support the construction and deployment of these kinds of higher-order concepts during learning. To address this question, we combined a carefully designed associative learning task with computational model-based functional magnetic resonance imaging (fMRI). Participants were scanned as they learned and made decisions about sixteen pairs of cues and associated outcomes. Associations were structured such that individual cues shared feature relationships, operationalized as shared patterns of cue pair-outcome associations. In order to capture the large number of possible conceptual representational structures that participants might employ and to evaluate how conceptual representations are used during learning, we leveraged a well-specified Bayesian computational model of category learning [1]. Behavioral and model-based results revealed that participants who displayed a tendency to link experiences in memory benefitted from faster learning rates, suggesting that the use of the conceptual structure in the task facilitated decisions about cue pair-outcome associations. Model-based fMRI analyses revealed that trial-by-trial integration of cue information into higher-order conceptual representations was supported by an anterior temporal (AT) network of regions previously implicated in representing complex conjunctions of features and meaning-based information.
A genome-wide innateness gradient defines the functional state of human innate T cells
Authors: Gutierrez-Arcelus M. , Teslovich N. , Mola A. R. , Kim H. , Hannes S. , Slowikowski K. , Watts G. F. M. , Brenner M. , Raychaudhuri S. , Brennan P. J. 
Published: March 2018

AbstractInnate T cells (ITCs), including invariant natural killer T (iNKT) cells, mucosal-associated invariant T (MAIT) cells, and γδ T cell populations, use conserved antigen receptors generated by somatic recombination to respond to non-peptide antigens in an innate-like manner. Understanding where these cells fit in the scheme of immunity has been a puzzle since their discovery. Here, immunophenotyping of 101 individuals revealed that these populations account for as much as 25% of peripheral human T cells. To better understand these cells, we generated detailed gene expression profiles using low-input RNA-seq and confirmed key findings through protein-level and functional validation. Unbiased transcriptomic analyses revealed a continuous ‘innateness gradient’ with adaptive T cells at one end followed by MAIT, iNKT, Vδ1+T, Vδ2+T, and natural killer cells at the other end. Innateness was characterized by decreased expression of translational machinery genes and reduced proliferative potential, which allowed for prioritization of effector functions, including rapid cytokine and chemokine production, and cytotoxicity. Thus, global transcriptional programs uncovered rapid proliferation and rapid effector functions as competing goals that respectively define adaptive and innate states.One Sentence SummaryAdaptive and innate T cells align along a continuous innateness gradient, reflecting a trade-off between effector function and proliferative capacity.
Passenger mutations in 2500 cancer genomes: Overall molecular functional impact and consequences
Authors: Kumar Sushant , Warrell Jonathan , Li Shantao , McGillivray Patrick D. , Meyerson William , Salichos Leonidas , Harmanci Arif , Martinez-Fundichely Alexander , Chan Calvin W.Y. , Nielsen Morten Muhlig , Lochovsky Lucas , Zhang Yan , Li Xiaotong , Pedersen Jakob Skou , Herrmann Carl , Getz Gad , Khurana Ekta , Gerstein Mark B. 
Published: March 2018

AbstractThe Pan-cancer Analysis of Whole Genomes (PCAWG) project provides an unprecedented opportunity to comprehensively characterize a vast set of uniformly annotated coding and non-coding mutations present in thousands of cancer genomes. Classical models of cancer progression posit that only a small number of these mutations strongly drive tumor progression and that the remaining ones (termed “putative passengers”) are inconsequential for tumorigenesis. In this study, we leveraged the comprehensive variant data from PCAWG to ascertain the molecular functional impact of each variant. The impact distribution of PCAWG mutations shows that, in addition to high- and low-impact mutations, there is a group of medium-impact putative passengers predicted to influence gene activity. Moreover, the predicted impact relates to the underlying mutational signature: different signatures confer divergent impact, differentially affecting distinct regulatory subsystems and gene categories. We also find that impact varies based on subclonal architecture (i.e., early vs. late mutations) and can be related to patient survival. Finally, we note that insufficient power due to limited cohort sizes precludes identification of weak drivers using standard recurrence-based approaches. To address this, we adapted an additive effects model derived from complex trait studies to show that aggregating the impact of putative passenger variants (i.e. including yet undetected weak drivers) provides significant predictability for cancer phenotypes beyond the PCAWG identified driver mutations (12.5% additive variance). Furthermore, this framework allowed us to estimate the frequency of potential weak driver mutations in the subset of PCAWG samples lacking well-characterized driver alterations.
From proteins to polysaccharides: lifestyle and genetic evolution ofCoprothermobacter proteolyticus
Authors: Kunath B. J. , Delogu F. , Naas A.E. , Arntzen M.Ø. , Eijsink V.G.H. , Henrissat B. , Hvidsten T.R. , Pope P.B. 
Published: March 2018

ABSTRACTMicrobial communities that degrade lignocellulosic biomass are typified by high levels of species- and strain-level complexity as well as synergistic interactions between both cellulolytic and non-cellulolytic microorganisms.Coprothermobacter proteolyticusfrequently dominates thermophilic, lignocellulose-degrading communities with wide geographical distribution, which is in contrast to reports that it ferments proteinaceous substrates and is incapable of polysaccharide hydrolysis. Here we deconvolute a highly efficient cellulose-degrading consortium (SEM1b) that is co-dominated byClostridium (Ruminiclostridium) thermocellum- and multiple heterogenic strains affiliated toC. proteolyticus. Metagenomic analysis of SEM1b recovered metagenome-assembled genomes (MAGs) for each constituent population, whilst in parallel two novel strains ofC. proteolyticuswere successfully isolated and sequenced. Annotation of allC. proteolyticusgenotypes (two strains and one MAG) revealed their genetic acquisition of carbohydrate-active enzymes (CAZymes), presumably derived from horizontal gene transfer (HGT) events involving polysaccharide-degrading Firmicutes or Thermotogae-affiliated populations that are historically co-located. HGT material included a saccharolytic operon, from which a CAZyme was biochemically characterized and demonstrated hydrolysis of multiple hemicellulose polysaccharides. Finally, temporal genome-resolved metatranscriptomic analysis of SEM1b revealed expression ofC. proteolyticusCAZymes at different SEM1b life-stages as well as co-expression of CAZymes from multiple SEM1b populations, inferring deeper microbial interactions that are dedicated towards community degradation of cellulose and hemicellulose. We show thatC. proteolyticus, a ubiquitous keystone population, consists of closely related strains that have adapted via HGT to presumably degrade both oligo- and longer polysaccharides present in decaying plants and microbial cell walls, thus explaining its dominance in thermophilic anaerobic digesters on a global scale.