bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Point-of-Care CD4 Testing on Retention in Care Among HIV-Positive Pregnant and Breastfeeding Women in the Context of Option B+ in Zimbabwe: A Cluster Randomized Controlled Trial
Authors: Joseph Jessica , Gotora Tendai , Erlwanger Alison S. , Mushavi Angela , Zizhou Simukai , Masuka Nyasha , Boeke Caroline E. , Mangwiro Alexio-Zambezi 
Published: May 2017

Introduction:
Scale-up of Option B+ in Zimbabwe has increased antiretroviral therapy (ART) coverage but patient loss-to-follow-up remains high; thus, effective strategies to improve retention in care are needed. Evidence for Elimination, a cluster randomized controlled trial, evaluated the impact of point-of-care (POC) CD4 testing with CD4 count-specific adherence counseling on rates of retention among 1150 HIV-positive pregnant women initiating ART in Zimbabwe.

Methods:
Thirty-two primary care health facilities were randomized to offer either standard-of-care (SOC) or POC CD4 testing plus CD4-specific counseling to clients (POC Plus). The primary outcome was the proportion of HIV-positive pregnant women retained on ART after 12 months, calculated by cluster-adjusted proportions, unadjusted and adjusted relative risks (RR and aRR, respectively).

Results:
Retention in care 12 months after initiation was 50.7% and 54.5% in the POC Plus and SOC arms, respectively (RR 0.93, 95% confidence interval [CI]: 0.78 to 1.11; aRR 0.91, 95% CI: 0.77 to 1.07). Although considered not retained, 9.7% transferred to another facility and 0.2% died. Most women, 95.3% in POC Plus and 92.9% in SOC, initiated ART within 1 month of antenatal booking (RR 1.03, 95% CI: 0.97 to 1.08).

Discussion:
Although patient retention was similar in both arms, women in the POC Plus arm were more likely to have received a CD4 test at booking and a repeat CD4 test later in care. CD4 is no longer required for treatment initiation but is still recommended in national guidelines and is of value in clinical management. Further work is needed to identify effective strategies to increase patient retention in ART care.
Long-term Outcomes of Carotid Endarterectomy Versus Stenting in a Multicenter Population-based Canadian Study
Authors: Hussain Mohamad A. , Mamdani Muhammad , Tu Jack V. , Saposnik Gustavo , Aljabri Badr , Bhatt Deepak L. , Verma Subodh , Al-Omran Mohammed 
Published: May 2017

Objective:
To compare the long-term outcomes of patients treated with carotid endarterectomy and carotid-artery stenting.

Background:
Evidence for the long-term safety and efficacy of carotid-artery stenting compared with endarterectomy is accumulating from randomized trials. However, comparative data on the long-term outcomes of carotid revascularization strategies in real world practice are lacking.

Methods:
We conducted a population-based, multicenter, observational cohort study using validated linked databases from Ontario, Canada. We identified all individuals treated with carotid endarterectomy and stenting (2002–2014), and followed them up to 2015. We compared long-term (up to 13 years) and 30-day outcomes of each strategy using multilevel multivariable Cox proportional-hazards models, and conducted confirmatory analyses using propensity-score matching methods.

Results:
In all, 15,525 patients received carotid-artery revascularization. Rate of the primary composite outcome of 30-day death, stroke, or myocardial infarction plus any stroke during 13-year follow-up was higher with stenting (16.3%) compared with endarterectomy (9.7%) [adjusted hazard ratio (HR) 1.57, 95% confidence interval (CI) 1.43–1.73, P < 0.001). The increased risk with stenting was observed regardless of age, sex, intervention year, carotid-artery symptoms, or diabetes. The primary outcome was driven by higher rates of 30-day stroke (adjusted HR 1.59, 95% CI 1.29–1.95), 30-day death (adjusted HR 2.62, 95% CI 2.20–3.13), and long-term stroke >30 days after the procedure (adjusted HR 1.47, 95% CI 1.36–1.59) with stenting; 30-day myocardial infarction was lower with stenting (adjusted HR 0.70, 95% CI 0.57–0.86). These results were confirmed with 1:2 propensity-score matching (HR for primary composite outcome with stenting 1.55, 95% CI 1.31–1.83, P < 0.001).

Conclusions:
Compared with carotid endarterectomy, stenting was associated with an early and sustained approximately 55% increased hazard for major adverse events over long-term follow-up. Although nonrandomized, these results raise potential concerns about the interchangeability of carotid endarterectomy and stenting in the context of actual clinical practice.
Kidney Transplant Recipients' Perspectives on Cardiovascular Disease and Related Risk Factors After Transplantation: A Qualitative Study
Authors: Ballesteros Fabián , Allard Julie , Durand Céline , Cardinal Héloïse , Lalonde Lyne , Fortin Marie-Chantal 
Published: May 2017

Background
Cardiovascular disease (CVD) is a major cause of mortality among kidney transplant recipients (KTRs). These patients have a high prevalence of risk factors, such as hypertension, diabetes, and dyslipidemia. Despite regular medical care, few of them reach the recommended therapeutic targets. The objective of this study is to describe KTRs' perspectives on CVD and related risk factors, as well as their priorities for posttransplant care.

Methods
Twenty-six KTRs participated in a semistructured interview about their personal experience and offered their perspectives on CVD risk factors posttransplant. The interview was digitally recorded and the transcripts were analyzed using a thematic and content methodology.

Results
CVD and related risk factors appear to be underestimated and trivialized. Only 2 of 26 patients identified CVD prevention and treatment as a priority. The most important posttransplant priorities identified by patients were related to immunosuppressive drugs (13 of 26), posttransplant follow-up (10) and graft survival (9). However, 21 of 26 patients stated they wanted to be better informed about posttransplant CVD risk factors.

Conclusions
CVD and related risk factors are not a priority for KTRs, and the importance of CVD is underestimated and trivialized. KTRs did recommend that tailored information be provided by various professionals and at several points in the transplantation process. This knowledge will help us develop a new approach to increase awareness of posttransplant CVD and related risk factors.
New neurosurgical approaches for tremor and Parkinson's disease
Authors: Fasano Alfonso , Lozano Andres M. , Cubo Esther 
Published: May 2017

Purpose of review
The objective of this review is to gather the newest advances in the surgical treatment of tremor and Parkinson's disease. We will briefly discuss the potential applications of the new technologies of deep brain stimulation (DBS), and we will focus on MRI-guided focused ultrasound (MRgFUS).

Recent findings
Novel DBS devices are being progressively adopted, particularly electrodes allowing a longer stimulating surface (suitable for multiple targets stimulation) and current radial steering (to minimize side effects of stimulation). New implantable pulse generators are also able to record neurons and are generating enough knowledge to advance the implementation of adaptive (closed-loop) DBS.
Over the last years, ‘minimally-invasive’ neurosurgical approaches for the treatment of movement disorders have been developed: gamma knife radiosurgery and MRgFUS. Uncontrolled and recent controlled studies have shown the benefits of MRgFUS targeting the thalamus and pallidus for the treatment of tremor and Parkinson's disease.

Summary
The initial clinical data are certainly promising and have expanded the current portfolio of neurosurgical treatments of movement disorders. Many issues are yet to be addressed, particularly safety of MRgFUS-and how these new treatments compare with the existing ones.
Characterization of amylase and protease activities in the digestive system ofConcholepas concholepas(Gastropoda, muricidae)
Authors: Gutierrez Alejandro P. , Cerda-Llanos Viviana , Forttes Diego , Carvajal Nelson , Uribe Elena A. 
Published: May 2017

ABSTRACTConcholepas concholepas(loco) is a carnivorous gastropod that inhabits the coast of Chile and Peru. Its fisheries showed a great importance in the past decades, however, now mainly relies on artisanal management of wild stocks. Feeding is one of the important factors that have restrained the establishment of large scale field rearing of loco.C. concholepasfood preferences consist of mytilids and cirripeds, however its digestive physiology has not been studied and its digestive enzymes have not been yet characterized. The purification of amylase and protease from the digestive gland and the gland of Leiblein ofC. concholepaswere performed by ionic exchange chromatography (DEAE-cellulose), and substrate-PAGE indicated the presence of the amylase and protease in the fractions collected from the column. Amylase enzymatic assays showed its maximum activity at pH 7.0 and 50°C in the digestive gland. Protease on the other hand showed a great acidic activity, specifically at pH 3.0 in both organs, also at 50°C. Inhibition of the amylolytic activity was observed in the presence of EDTA, and metal ions like MnCl2, MgCl2, ZnSO4, while it was enhanced in the presence of CaCl2, NaCl, KCl. Protease inhibition assays were also performed evidencing mainly the presence of aspartic proteases and a low but not inexistent presence of serine proteases. Our results provide evidence of important proteolytic but also amylolytic activities present in the digestive system of loco, providing evidence that this mollusc has wider digestive capabilities than initially though, which could potentially lead to the development of alternative food diets.
Neuronal upregulation of Prospero protein is driven by alternative mRNA polyadenylation and Syncrip-mediated mRNA stabilisation
Authors: Samuels Tamsin J. , Arava Yoav , Järvelin Aino I. , Robertson Francesca , Lee Jeffrey Y. , Yang Lu , Yang Ching-Po , Lee Tzumin , Ish-Horowicz David , Davis Ilan 
Published: May 2017

ABSTRACTDuringDrosophilaand vertebrate brain development, the conserved transcription factor Prospero/Prox1 is an important regulator of the transition between proliferation and differentiation. Prospero level is low in neural stem cells and their immediate progeny, but is upregulated in larval neurons and it is unknown how this process is controlled. Here, we use single molecule fluorescentin situhybridisation to show that larval neurons selectively transcribe a longprosperomRNA isoform containing a 15 kb 3’ untranslated region, which is bound in the brain by the conserved RNA-binding protein Syncrip/hnRNPQ. Syncrip binding increases the mRNA stability of the longprosperoisoform, which allows an upregulation of Prospero protein production. Our findings highlight a regulatory strategy involving alternative polyadenylation followed by differential post-transcriptional regulation.
Millisecond dynamics of BTK reveal kinome-wide conformational plasticity within the apo kinase domain
Authors: Sultan Mohammad M. , Denny Rajiah Aldrin , Unwalla Ray , Lovering Frank , Pande Vijay S. 
Published: May 2017

AbstractBruton tyrosine kinase (BTK) is a key enzyme in B-cell development whose improper regulation causes severe immunodeficiency diseases. Design of selective BTK therapeutics would benefit from improved,in-silicostructural modeling of the kinase’s solution ensemble. However, this remains challenging due to the immense computational cost of sampling events on biological timescales. In this work, we combine multi-millisecond molecular dynamics (MD) simulations with Markov state models (MSMs) to report on the thermodynamics, kinetics, and accessible states of BTK’s kinase domain. Our conformational landscape links the active state to several inactive states, connected via a structurally diverse intermediate. Our calculations predict a kinome-wide conformational plasticity, and indicate the presence of several new potentially druggable BTK states. We further find that the population of these states and the kinetics of their inter-conversion are modulated by protonation of an aspartate residue, establishing the power of MD & MSMs in predicting effects of chemical perturbations.
Prominent features of the amino acid mutation landscape in cancer
Authors: Szpiech Zachary A. , Strauli Nicolas B. , White Katharine A. , Ruiz Diego Garrido , Jacobson Matthew P. , Barber Diane L. , Hernandez Ryan D. 
Published: May 2017

ABSTRACTCancer can be viewed as a set of different diseases with distinctions based on tissue origin, driver mutations, and genetic signatures. Accordingly, each of these distinctions have been used to classify cancer subtypes and to reveal common features. Here, we present a different analysis of cancer based on amino acid mutation signatures. Non-negative Matrix Factorization and principal component analysis of 29 cancers revealed six amino acid mutation signatures, including four signatures that were dominated by either arginine to histidine (Arg>His) or glutamate to lysine (Glu>Lys) mutations. Sample-level analyses reveal that while some cancers are heterogeneous, others are largely dominated by one type of mutation. Using a non-overlapping set of samples from the COSMIC somatic mutation database, we validate five of six mutation signatures, including signatures with prominent arginine to histidine (Arg>His) or glutamate to lysine (Glu>Lys) mutations. This suggests that our classification of cancers based on amino acid mutation patterns may provide avenues of inquiry pertaining to specific protein mutations that may generate novel insights into cancer biology.
Genome-wide Association Study Of Plasma Proteins Identifies Putatively Causal Genes, Proteins, And Pathways For Cardiovascular Disease
Authors: Yao Chen , Chen George , Song Ci , Mendelson Michael , Huan Tianxiao , Laser Annika , Wu Hongsheng , Ho Jennifer E. , Courchesne Paul , Lyass Asya , Larson Martin G. , Gieger Christian , Graumann Johannes , Johnson Andrew D. , Hwang Shih-Jen , Liu Chunyu , Suhre Karsten , Levy Daniel 
Published: May 2017

SummaryIdentifying genetic variants associated with circulating protein concentrations (pQTLs) and integrating them with variants from genome-wide association studies (GWAS) may illuminate the proteome’s causal role in disease and bridge a GWAS knowledge gap for hitherto unexplained SNP-disease associations. We conducted GWAS of 71 high-value proteins for cardiovascular disease in 6,861 Framingham Heart Study participants followed by external replication. We comprehensively mapped thousands of pQTLs, including functional annotations and clinical-trait associations, and created an integrated plasma-protein-QTL searchable database. We next identified 15 proteins with pQTLs coinciding with coronary heart disease (CHD)-related variants from GWAS or tested causal for CHD by Mendelian randomization; most of these proteins were associated with new-onset cardiovascular disease events in Framingham participants with long-term follow-up. Identifying pQTLs and integrating them with GWAS results yields insights into genes, proteins, and pathways that may be causally associated with disease and can serve as therapeutic targets for treatment and prevention.
A simple representation of three-dimensional molecular structure
Authors: Axen Seth D. , Huang Xi-Ping , Cáceres Elena L. , Gendelev Leo , Roth Bryan L. , Keiser Michael J. 
Published: May 2017

AbstractStatistical and machine learning approaches predict drug-to-target relationships from 2D small-molecule topology patterns. One might expect 3D information to improve these calculations. Here we apply the logic of the Extended Connectivity FingerPrint (ECFP) to develop a rapid, alignment-invariant 3D representation of molecular conformers, the Extended Three-Dimensional FingerPrint (E3FP). By integrating E3FP with the Similarity Ensemble Approach (SEA), we achieve higher precision-recall performance relative to SEA with ECFP on ChEMBL20, and equivalent receiver operating characteristic performance. We identify classes of molecules for which E3FP is a better predictor of similarity in bioactivity than is ECFP. Finally, we report novel drug-to-target binding predictions inaccessible by 2D fingerprints and confirm three of them experimentally with ligand efficiencies from 0.442 - 0.637 kcal/mol/heavy atom.
A novel reporter allele for monitoringDll4expression within the embryonic and adult mouse
Authors: Herman Alexander M. , Rhyner Alexander M. , Devine W. Patrick , Marrelli Sean P. , Bruneau Benoit G. , Wythe Joshua D. 
Published: May 2017

AbstractCanonical Notch signaling requires the presence of a membrane bound ligand and a corresponding transmembrane Notch receptor. Receptor engagement induces multiple proteolytic cleavage events culminating in the nuclear accumulation of the Notch intracellular domain and its binding to a transcriptional co-factor to mediate gene expression. Notch signaling networks are essential regulators of vascular patterning and angiogenesis, as well as myriad other biological processes.Delta-like 4(Dll4) encodes the earliest Notch ligand detected in arterial cells, and is enriched in sprouting endothelial tip cells.Dll4expression has often been inferred by proxy using alacZknockin reporter allele. This is problematic, as a single copy ofDll4is haploinsufficient. Additionally, Notch activity regulatesDll4transcription, making it unclear whether these reporter lines accurately reflectDll4expression. Accordingly, accurately definingDll4expression is essential for determining its role in development and disease. To address these limitations, we generated a novel BAC transgenic allele with a nuclear-localized β-galactosidase reporter (Dll4-BAC-nlacZ). Through a comparative analysis, we show the BAC line overcomes previous issues of haploinsufficiency, it recapitulatesDll4expressionin vivo, and allows superior visualization and imaging. As such, this novelDll4reporter is an important addition to the growing Notch toolkit.Summary Statement:We have developed a novel reporter line, free from complicating factors associated with previous alleles, for monitoringDll4expression, at a cellular resolution, in the developing and adult mouse.
Scc2/Nipbl hops between chromosomal cohesin rings after loading
Authors: Rhodes James D.P. , Mazza Davide , Nasmyth Kim A. , Uphoff Stephan 
Published: May 2017

AbstractThe cohesin complex mediates DNA-DNA interactions both between (sister chromatid cohesion) and within chromosomes (DNA looping) via a process thought to involve entrapment of DNAs within its tripartite ring. It has been suggested that intra- chromosome loops are generated through processive extrusion of DNAs through the lumen of cohesin’s ring. Scc2 (Nipbl) is essential for loading cohesin onto chromosomes but not for maintaining sister chromatid cohesion following DNA replication. It has therefore been assumed that Scc2 is involved exclusively in the cohesin loading process. However, it is possible that the stimulation of cohesin’s ABC-like ATPase by Scc2 also has a post-loading function, for example driving loop extrusion. Using fluorescence recovery after photobleaching (FRAP) and single-molecule tracking, we show that Scc2 binds dynamically to chromatin, principally through an association with cohesin. Scc2’s movement within chromatin is consistent with a “stop-and-go” or “hopping” motion. We suggest that a low diffusion coefficient, a low stoichiometry relative to cohesin, and a high affinity for chromosomal cohesin enables Scc2 to move rapidly from one chromosomal cohesin complex to another, performing a function distinct from loading.
Global phylogenetic analysis of Escherichia coli and plasmids carrying the mcr-1 gene indicates bacterial diversity but plasmid restriction
Authors: Matamoros Sébastien , van Hattem Jarne M. , Arcilla Maris S. , Willemse Niels , Melles Damian C. , Penders John , Nguyen Vinh Trung , Hoa Ngo Thi , de Jong Menno D. , Schultsz Constance , Bootsma Martin C.J. , van Genderen Perry J. , Goorhuis Abraham , Grobusch Martin P. , Molhoek Nicky , Oude Lashof Astrid M.L. , Stobberingh Ellen E. , Verbrugh Henri A. 
Published: May 2017

AbstractTo understand the dynamics behind the worldwide spread of the mcr-1 gene, we determined the population structure of Escherichia coli and of mobile genetic elements (MGEs) carrying the mcr-1 gene. After a systematic review of the literature we included 65 E. coli whole genome sequences (WGS), adding 6 recently sequenced travel related isolates, and 312 MLST profiles. We included 219 MGEs described in 7 Enterobacteriaceae species isolated from human, animal and environmental samples. Despite a high overall diversity, 2 lineages were observed in the E. coli population that may function as reservoirs of the mcr-1 gene, the largest of which was linked to ST10, a sequence type known for its ubiquity in human faecal samples and in food samples. No genotypic clustering by geographical origin or isolation source was observed. Amongst a total of 13 plasmid incompatibility types, the Incl2, lncX4 and IncHI2 plasmids accounted for more than 90% of MGEs carrying the mcr-1 gene. We observed significant geographical clustering with regional spread of lncHI2 plasmids in Europe and Incl2 in Asia. These findings point towards promiscuous spread of the mcr-1 gene by efficient horizontal gene transfer dominated by a limited number of plasmid incompatibility types.
Neurophysiological Correlates of the Rubber Hand Illusion in Evoked and Oscillatory Brain Activity
Authors: Rao Isa S. , Kayser Christoph 
Published: May 2017

AbstractThe rubber hand illusion (RHI) allows insights into how the brain resolves conflicting multisensory information regarding body position and ownership. Previous neuroimaging studies have reported a variety of neurophysiological correlates of illusory hand ownership, with conflicting results likely originating from differences in experimental parameters and control conditions. Here, we overcome these limitations by using a fully automated and precisely-timed visuo-tactile stimulation setup to record evoked responses and oscillatory responses in the human EEG. Importantly, we relied on a combination of experimental conditions to rule out confounds of attention, body-stimulus position and stimulus duration, and on the combination of two control conditions to identify neurophysiological correlates of illusory hand ownership. In two separate experiments we observed a consistent illusion-related attenuation of ERPs around 330 ms over frontocentral electrodes, as well as decreases of frontal alpha and beta power during the illusion that could not be attributed to changes in attention, body-stimulus position or stimulus duration. Our results reveal neural correlates of illusory hand ownership in late and likely higher-order rather than early sensory processes, and support a role of premotor and possibly intraparietal areas in mediating illusory body ownership.