bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antihypertensive Drugs Aliskiren, Nebivolol, and Olmesartan Reduce Hypertension by Reducing Endothelial Microparticles and Regulating Angiogenesis
Authors: Jain Moon , Bhosale Vivek , Tripathi Dipti , Singh Himalaya , Pal Niharika , Hanif Kashif , Jagavelu Kumaravelu 
Published: May 2017

Abstract
The accelerated generation of endothelial microparticles (EMPs) and impaired angiogenesis are the markers of vascular pathology during various cardiovascular and inflammatory conditions including hypertension. Because studies comparing the effects of antihypertensive agents on these 2 parameters are limited, this study was designed to compare the effects of 3 antihypertensive agents: aliskiren, nebivolol, and olmesartan, on the EMP generation and angiogenesis. Changes in the hemodynamic parameters and serum EMP count were determined after 3 weeks of the drug treatments [aliskiren (30 mg/kg), nebivolol (10 mg/kg), or olmesartan (5 mg/kg) per orally] in l-NAME–induced rat model of hypertension. The 3 drugs prevented the rise in blood pressure and EMP count to a similar extent. Furthermore, nebivolol was found to possess more potent and concentration-dependent antiangiogenic activity compared with aliskiren, whereas olmesartan was devoid of such an effect. The EMPs generated by virtue of the respective drug treatments were found to be involved in mediating the antiangiogenic effect of nebivolol and aliskiren. In addition, olmesartan treatment also resulted in the increased eNOS expression. The results of this study show that the antihypertensive drugs, viz. aliskiren, nebivolol, and olmesartan, regulate the vascular health by their differential effects on the EMP generation and angiogenesis.
A PROSPECTIVE, RANDOMIZED TRIAL COMPARING PLAIN GUT TO POLYGLACTIN 910 (VICRYL) SUTURES FOR SCLEROTOMY CLOSURE AFTER 23-GAUGE PARS PLANA VITRECTOMY
Authors: Sridhar Jayanth , Kasi Sundeep , Paul Joshua , Shahlaee Abtin , Rahimy Ehsan , Chiang Allen , Spirn Marc J. , Hsu Jason , Garg Sunir J. ,   on behalf of the Retina Service of Wills Eye Hospital Vitrectomy Study Group
Published: May 2017

Purpose:
To report a prospective, randomized comparative study assessing clinical outcomes of plain gut versus polyglactin 910 (PG910) sutures for sclerotomy closure after 23-gauge pars plana vitrectomy.

Methods:
A single-masked, randomized, prospective study was undertaken with 49 eyes of 49 patients undergoing 23-gauge pars plana vitrectomy randomized to sclerotomy closure with either plain gut suture, PG910 (Vicryl) suture or a combination of the two. Assessment was based on both a postoperative pain scale and a standardized assessment of scleral inflammation at each suture site.

Results:
No wound leakage was noted postoperatively in any patient. Across all groups, scleral inflammation was significantly higher at the PG910 suture sites compared with the plain gut suture sites at both the 1-week (P = 0.04) and 1-month postoperative visits (P < 0.001). Patients with PG910 sutures reported greater pain at the 1-month postoperative visit than those with plain gut sutures (P = 0.018).

Conclusion:
This prospective study suggests improved tolerability and reduced inflammation using plain gut suture compared with an 8-0 PG910 suture to close 23-gauge sclerotomies.
THREE-DIMENSIONAL ANALYSIS OF SUBMACULAR PERFORATING SCLERAL VESSELS BY ENHANCED DEPTH IMAGING OPTICAL COHERENCE TOMOGRAPHY
Authors: Rothenbuehler Simon P. , Maloca Peter , Scholl Hendrik P. N. , Gyger Cyrill , Schoetzau Andreas , Kuske Lorenz , Mosimann Nathanael , Zweifel Sandrine A. , Barthelmes Daniel , Tufail Adnan , Hasler Pascal W. 
Published: May 2017

Purpose:
To analyze submacular perforating scleral vessels (PSVs) using enhanced depth imaging spectral domain optical coherence tomography (EDI-SDOCT).

Methods:
Twenty-two eyes of 11 healthy women were included in this retrospective study. Central EDI-SDOCT scans (3 × 4.5 × 1.9 mm, 13.5 mm2 scan area) were acquired and postprocessed by denoising, manual sclera segmentation, and PSV investigated by five graders.

Results:
Mean age was 22.4 ± 6.2 years. Mean refractive error was −0.44 ± 0.8 diopters. Mean axial length was 23.08 ± 0.63 mm. The coefficient of agreement for grading was good. Mean number of submacular PSVs was 0.33 ± 0.2 per mm2 (range from 0 to 9 per eye). Subfield analysis showed 0.2 ± 0.5 (range 0–2) and 2.1 ± 1.8 (range 0–7) vessels, respectively, for central 1-mm diameter and 3-mm diameter. Quadrant analysis showed 0.7 ± 0.9, 0.5 ± 0.9, 0.3 ± 0.6, and 0.4 ± 0.6 vessels, respectively for superior, inferior, nasal, and temporal quadrants. Total number of PSV showed no significant side difference (median difference 0.5, confidence interval −3.0 to 3.0, P = 0.94) or an influence of axial length (P = 0.16).

Conclusion:
This is the first description of three-dimensional EDI-SDOCT visualization of submacular PSV in healthy eyes. This method allows for in vivo imaging of a critical component of outer retinal perfusion at the posterior pole.
Incorporating Alternative Care Site Characteristics Into Estimates of Substitutable ED Visits
Authors: Trueger Nathan Seth , Chua Kao-Ping , Hussain Aamir , Liferidge Aisha T. , Pitts Stephen R. , Pines Jesse M. 
Published: May 2017

Background:
Several recent efforts to improve health care value have focused on reducing emergency department (ED) visits that potentially could be treated in alternative care sites (ie, primary care offices, retail clinics, and urgent care centers). Estimates of the number of these visits may depend on assumptions regarding the operating hours and functional capabilities of alternative care sites. However, methods to account for the variability in these characteristics have not been developed.

Objective:
To develop methods to incorporate the variability in alternative care site characteristics into estimates of ED visit “substitutability.”

Research Design, Subjects, and Measures:
Our approach uses the range of hours and capabilities among alternative care sites to estimate lower and upper bounds of ED visit substitutability. We constructed “basic” and “extended” criteria that captured the plausible degree of variation in each site’s hours and capabilities. To illustrate our approach, we analyzed data from 22,697 ED visits by adults in the 2011 National Hospital Ambulatory Medical Care Survey, defining a visit as substitutable if it was treat-and-release and met both the operating hours and functional capabilities criteria.

Results:
Use of the combined basic hours/basic capabilities criteria and extended hours/extended capabilities generated lower and upper bounds of estimates. Our criteria classified 5.5%–27.1%, 7.6%–20.4%, and 10.6%–46.0% of visits as substitutable in primary care offices, retail clinics, and urgent care centers, respectively.

Conclusions:
Alternative care sites vary widely in operating hours and functional capabilities. Methods such as ours may help incorporate this variability into estimates of ED visit substitutability.
Identifying Increased Risk of Readmission and In-hospital Mortality Using Hospital Administrative Data
Authors: Moore Brian J. , White Susan , Washington Raynard , Coenen Natalia , Elixhauser Anne 
Published: May 2017

Objective:
We extend the literature on comorbidity measurement by developing 2 indices, based on the Elixhauser Comorbidity measures, designed to predict 2 frequently reported health outcomes: in-hospital mortality and 30-day readmission in administrative data. The Elixhauser measures are commonly used in research as an adjustment factor to control for severity of illness.

Data Sources:
We used a large analysis file built from all-payer hospital administrative data in the Healthcare Cost and Utilization Project State Inpatient Databases from 18 states in 2011 and 2012.

Methods:
The final models were derived with bootstrapped replications of backward stepwise logistic regressions on each outcome. Odds ratios and index weights were generated for each Elixhauser comorbidity to create a single index score per record for mortality and readmissions. Model validation was conducted with c-statistics.

Results:
Our index scores performed as well as using all 29 Elixhauser comorbidity variables separately. The c-statistic for our index scores without inclusion of other covariates was 0.777 (95% confidence interval, 0.776–0.778) for the mortality index and 0.634 (95% confidence interval, 0.633–0.634) for the readmissions index. The indices were stable across multiple subsamples defined by demographic characteristics or clinical condition. The addition of other commonly used covariates (age, sex, expected payer) improved discrimination modestly.

Conclusions:
These indices are effective methods to incorporate the influence of comorbid conditions in models designed to assess the risk of in-hospital mortality and readmission using administrative data with limited clinical information, especially when small samples sizes are an issue.
Acute Kidney Injury After Pediatric Cardiac Surgery: A Secondary Analysis of the Safe Pediatric Euglycemia After Cardiac Surgery Trial*
Authors: Blinder Joshua J. , Asaro Lisa A. , Wypij David , Selewski David T. , Agus Michael S. D. , Gaies Michael , Ferguson Michael A. 
Published: May 2017

Objectives:
To understand the effect of tight glycemic control on cardiac surgery–associated acute kidney injury.

Design:
Secondary analysis of data from the Safe Pediatric Euglycemia after Cardiac Surgery trial of tight glycemic control versus standard care.

Setting:
Pediatric cardiac ICUs at University of Michigan, C.S. Mott Children’s Hospital, and Boston Children’s Hospital.

Patients:
Children 0–36 months old undergoing congenital cardiac surgery.

Interventions:
None.

Measurements and Main Results:
Cardiac surgery–associated acute kidney injury was assigned using the Acute Kidney Injury Network criteria with the modification that a greater than 0.1 mg/dL increase in serum creatinine was required to assign cardiac surgery–associated acute kidney injury. We explored associations between cardiac surgery–associated acute kidney injury and tight glycemic control and clinical outcomes. Of 799 patients studied, cardiac surgery–associated acute kidney injury occurred in 289 patients (36%), most of whom had stage II or III disease (72%). Cardiac surgery–associated acute kidney injury rates were similar between treatment groups (36% vs 36%; p = 0.99). Multivariable modeling showed that patients with cardiac surgery–associated acute kidney injury were younger (p = 0.002), underwent more complex surgery (p = 0.005), and had longer cardiopulmonary bypass times (p = 0.002). Cardiac surgery–associated acute kidney injury was associated with longer mechanical ventilation and ICU and hospital stays and increased mortality. Patients at University of Michigan had higher rates of cardiac surgery–associated acute kidney injury compared with Boston Children’s Hospital patients (66% vs 15%; p < 0.001), but University of Michigan patients with cardiac surgery–associated acute kidney injury had shorter time to extubation and ICU and hospital stays compared with Boston Children’s Hospital patients.

Conclusions:
Tight glycemic control did not reduce the cardiac surgery–associated acute kidney injury rate in this trial cohort. We observed significant differences in cardiac surgery–associated acute kidney injury rates between the two study sites, and there was a differential effect of cardiac surgery–associated acute kidney injury on clinical outcomes by site. These findings warrant further investigation to identify causal variation in perioperative practices that affect cardiac surgery–associated acute kidney injury epidemiology.
Epinephrine Auto-Injector Versus Drawn Up Epinephrine for Anaphylaxis Management: A Scoping Review*
Authors: Chime Nnenna O. , Riese Victoria G. , Scherzer Daniel J. , Perretta Julianne S. , McNamara LeAnn , Rosen Michael A. , Hunt Elizabeth A. 
Published: May 2017

Objective:
Anaphylaxis is a life-threatening event. Most clinical symptoms of anaphylaxis can be reversed by prompt intramuscular administration of epinephrine using an auto-injector or epinephrine drawn up in a syringe and delays and errors may be fatal. The aim of this scoping review is to identify and compare errors associated with use of epinephrine drawn up in a syringe versus epinephrine auto-injectors in order to assist hospitals as they choose which approach minimizes risk of adverse events for their patients.

Data Sources:
PubMed, Embase, CINAHL, Web of Science, and the Cochrane Library were searched using terms agreed to a priori.

Study Selection:
We reviewed human and simulation studies reporting errors associated with the use of epinephrine in anaphylaxis. There were multiple screening stages with evolving feedback.

Data Extraction:
Each study was independently assessed by two reviewers for eligibility. Data were extracted using an instrument modeled from the Zaza et al instrument and grouped into themes.

Data Synthesis:
Three main themes were noted: 1) ergonomics, 2) dosing errors, and 3) errors due to route of administration. Significant knowledge gaps in the operation of epinephrine auto-injectors among healthcare providers, patients, and caregivers were identified. For epinephrine in a syringe, there were more frequent reports of incorrect dosing and erroneous IV administration with associated adverse cardiac events. For the epinephrine auto-injector, unintentional administration to the digit was an error reported on multiple occasions.

Conclusions:
This scoping review highlights knowledge gaps and a diverse set of errors regardless of the approach to epinephrine preparation during management of anaphylaxis. There are more potentially life-threatening errors reported for epinephrine drawn up in a syringe than with the auto-injectors. The impact of these knowledge gaps and potentially fatal errors on patient outcomes, cost, and quality of care is worthy of further investigation.
Increasing Patient-Clinician Concordance About Medical Error Disclosure Through the Patient TIPS Model
Authors: Martinez William , Browning David , Varrin Pamela , Sarnoff Lee Barbara , Bell Sigall K. 
Published: May 2017

Objective
To test whether an educational model involving patients and family members (P/F) in medical error disclosure training for interprofessional clinicians can narrow existing gaps between clinician and P/F views about disclosure.

Method
Parallel presurveys/postsurveys using Likert scale questions for clinicians and P/F.

Results
Baseline surveys were completed by 91% (50/55) of clinicians who attended the workshops and 74% (65/88) of P/F from a hospital patient and family advisory council. P/F’s baseline views about disclosure were significantly different from clinicians’ in 70% (7/10) of the disclosure expectation items and 100% (3/3) of the disclosure vignette items. For example, compared with clinicians, P/F more strongly agreed that “patients want to know all the details of what happened” and more strongly disagreed that “patients find explanation(s) more confusing than helpful.” In the medication error vignette, compared with clinicians, P/F more strongly agreed that the error should be disclosed and that the patient would want to know and more strongly disagreed that disclosure would do more harm than good (all P < 0.05). After the workshop, P/F and clinician views about information sharing, fallibility, truth telling, and threshold for disclosure showed greater concordance, with significant differences remaining in less than half of the expectation items and none of the vignette responses.

Discussion
Even with self-selecting clinicians, collaborative learning with P/F highlights important differences in patient and clinician baseline perspectives about medical error disclosure and brings patient and clinicians views closer together.
Description of Malignancy Rates in Childhood- and Adult-Onset Systemic Lupus Erythematous by Proportional Meta-analysis
Authors: Aoki Priscila Rodrigues da Silva , El Dib Regina , Silva Clovis Artur Almeida , Magalhaes Claudia Saad 
Published: May 2017

Objective
Describe malignancy rates in childhood onset and adult onset systemic lupus erythematous (SLE) by proportional meta-analysis.

Methods
Two reviewers screened data from PubMed (1966–2015), EMBASE (1980–2015), and LILACS (1982–2015) for SLE-associated malignancy. Proportional meta-analysis with a random-effects model and 95% confidence intervals (CIs) were calculated according to SLE onset age and mean follow-up time. Statistical difference was defined by 95% CI overlap.

Results
Overall the malignancy rate reported in 30 case series with 96,578 subjects was 3.4% (95% CI, 0.0260–0.0442; I
2 = 97.6%; P < 0.0001). The malignancy rate was 4.2% (95% CI, 0.0318–0.0531; I
2 = 98%; P < 0.0001) in 25 adult-onset SLE series, compared with 0.5% (95% CI, 0.0003–0.0154; I
2 = 62.6%; P = 0.03) in 5 childhood-onset SLE series. Overall, in those with less than 5 years’ follow-up, the malignancy rate was 2.8% (95% CI, 0.013–0.047; I
2 = 91%; P < 0.0001) compared with 3.6% (95% CI, 0.0226–0.0531; I
2 = 98.3%; P < 0.0001) in those with more than 5 years’ follow-up, which was not significant, with 95% CI overlap.

Conclusions
The meta-analysis indicated lower malignancy rates in pediatric-onset SLE compared with adult-onset SLE, but accrued data from childhood-onset SLE are still needed.
Disentangling the causes for faster-X evolution in aphids
Authors: Jaquiéry J , Peccoud J , Ouisse T , Legeai F , Prunier-Leterme N , Gouin A , Nouhaud P , Brisson JA , Bickel R , Purandare S , Poulain J , Battail C , Lemaitre C , Mieuzet L , Le Trionnaire G , Simon JC , Rispe C 
Published: May 2017

AbstractFaster evolution of X chromosomes has been documented in several species and results from the increased efficiency of selection on recessive alleles in hemizygous males and/or from increased drift due to the smaller effective population size of X chromosomes. Aphids are excellent models for evaluating the importance of selection in faster-X evolution, because their peculiar life-cycle and unusual inheritance of sex-chromosomes lead to equal effective population sizes for X and autosomes. Because we lack a high-density genetic map for the pea aphid whose complete genome has been sequenced, we assigned its entire genome to the X and autosomes based on ratios of sequencing depth in males and females. Unexpectedly, we found frequent scaffold misassembly, but we could unambiguously locate 13,726 genes on the X and 19,263 on autosomes. We found higher non-synonymous to synonymous substitutions ratios(dN/dS) for X-linked than for autosomal genes. Our analyses of substitution rates together with polymorphism and expression data showed that relaxed selection is likely to contribute predominantly to faster-X as a large fraction of X-linked genes are expressed at low rates and thus escape selection. Yet, a minor role for positive selection is also suggested by the difference between substitution rates for X and autosomes for male-biased genes (but not for asexual female-biased genes) and by lower Tajima’s D for X-linked than for autosomal genes with highly male-biased expression patterns. This study highlights the relevance of organisms displaying alternative inheritance of chromosomes to the understanding of forces shaping genome evolution.
High Resolution Epigenomic Atlas of Early Human Craniofacial Development
Authors: Wilderman Andrea , Kron Jeffrey , VanOudenhove Jennifer , Noonan James P. , Cotney Justin 
Published: May 2017

AbstractDefects in embryonic patterning resulting in craniofacial abnormalities are common birth defects affecting up to 1 in 500 live births worldwide, and are mostly non-syndromic. The regulatory programs that build and shape the craniofacial complex are thought to be controlled by information encoded in the genome between genes and within intronic sequences. Early stages of human craniofacial development have not been interrogated with modern functional genomics techniques, preventing systematic analysis of genetic associations with craniofacial-specific regulatory sequences. Here we describe a comprehensive resource of craniofacial epigenomic annotations and systematic, integrative analysis with a variety of human tissues and cell types. We identified thousands of novel craniofacial enhancers and provide easily accessible genome annotations for craniofacial researchers and clinicians. We demonstrate the utility of our data to find likely causal variants for craniofacial abnormalities and identify a large enhancer cluster that interacts with HOXA genes during craniofacial development.
De novoassembly and annotation of the eastern fence lizard (Sceloporus undulatus) transcriptome
Authors: Grizante Mariana B. , Tollis Marc , Rodriguez Juan J. , Levy Ofir , Angilletta Michael J. , Kusumi Kenro 
Published: May 2017

AbstractBackgroundThe eastern fence lizard (Sceloporus undulatus) has been a model species for ecological and evolutionary research. Genomic and transcriptomic resources for this species would promote investigation of genetic mechanisms that underpin plastic responses to environmental stress, such as climate warming. Moreover, such resources would aid comparative studies of complex traits at the molecular level, such as the transition from oviparous to viviparous reproduction, which happened at least four times withinSceloporus.FindingsAde novotranscriptome assembly forSceloporus undulatus, Sund_v1.0, was generated using over 179 million Illumina reads obtained from three tissues (whole brain, skeletal muscle, and embryo) as well as previously reported liver sequences. The Sund_v1.0 assembly had an average contig length of 782 nucleotides and an E90N50 statistic of 2,550 nucleotides. ComparingS. undulatustranscripts with the benchmarking universal single-copy orthologs (BUSCO) for tetrapod species yielded 97.2% gene representation. A total of 13,422 protein-coding orthologs were identified in comparison to the genome of the green anole lizard,Anolis carolinensis, which is the closest related species with genomic data available.ConclusionsThe multi-tissue transcriptome ofS. undulatusis the first for a member of the family Phrynosomatidae, offering an important resource to advance studies of adaptation in this species and genomic research in reptiles.
Inferring relevant cell types for complex traits using single-cell gene expression
Authors: Calderon Diego , Bhaskar Anand , Knowles David A. , Golan David , Raj Towfique , Fu Audrey Q. , Pritchard Jonathan K. 
Published: May 2017

AbstractPrevious studies have prioritized trait-relevant cell types by looking for an enrichment of GWAS signal within functional regions. However, these studies are limited in cell resolution by the lack of functional annotations from difficult-to-characterize or rare cell populations. Measurement of single-cell gene expression has become a popular method for characterizing novel cell types, and yet, hardly any work exists linking single-cell RNA-seq to phenotypes of interest. To address this deficiency, we presentRolyPoly, a regression-based polygenic model that can prioritize trait-relevant cell types and genes from GWAS summary statistics and single-cell RNA-seq. We demonstrateRolyPoly’s accuracy through simulation and validate previously known tissue-trait associations. We discover a significant association between microglia and late-onset Alzheimer’s disease, and an association between oligodendrocytes and replicating fetal cortical cells with schizophrenia. Additionally,RolyPolycomputes a trait-relevance score for each gene which reflects the importance of expression specific to a cell type. We found that differentially expressed genes in the prefrontal cortex of Alzheimer’s patients were significantly enriched for highly ranked genes byRolyPolygene scores. Overall, our method represents a powerful framework for understanding the effect of common variants on cell types contributing to complex traits.