bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating exosome microRNA associated with heart failure secondary to myxomatous mitral valve disease in a naturally occurring canine model
Authors: Yang Vicky K. , Loughran Kerry A. , Meola Dawn M. , Juhr Christine M. , Thane Kristen E. , Davis Airiel M. , Hoffman Andrew M. 
Published: July 2017

ABSTRACTMyxomatous mitral valve disease (MMVD) is functionally and histologically identical to mitral valve prolapse (MVP) in humans. Currently, there are no medical treatments that can delay the progression of this valvular disease or associated cardiac remodelling. Therefore, there is a need to understand the molecular pathology associated with MMVD and MVP better, and thus identify potential therapeutic targets. Circulating exosomes contain small RNA, including miRNA, which reflect cell physiology and pathology. This study explored the association between circulating exosomal miRNA (ex‐miRNA) content and MMVD, heart failure due to MMVD (MMVD‐CHF) and ageing, which is strongly associated with MMVD. Ex‐miRNA was isolated from old normal/healthy dogs (n = 6), young normal dogs (n = 7), dogs with MMVD (n = 7) and dogs with MMVD‐CHF (n = 7). Separately, total plasma miRNA was isolated from normal dogs (n = 8), dogs with MMVD (n = 8) and dogs with MMVD‐CHF (n = 11). Using reverse transcription quantitative polymerase chain reaction, exosomal miR‐181c (p = 0.003) and miR‐495 (p = 0.0001) significantly increased in dogs with MMVD‐CHF compared to the other three groups. Exosomal miR‐9 (p = 0.002) increased in dogs with MMVD and MMVD‐CHF compared to age‐matched (old) normal dogs. Exosomal miR‐599 (p = 0.002) decreased in dogs with MMVD compared to old normal dogs. In total plasma, 58 miRNA were deemed significantly different (p < 0.04) between normal dogs, dogs with MMVD and dogs with MMVD‐CHF. However, in contrast to ex‐miRNA, none of the miRNA in total plasma remained statistically significant if the false discovery rate was <15%. Changes in ex‐miRNA are observed in dogs as they age (miR‐9, miR‐495 and miR‐599), develop MMVD (miR‐9 and miR‐599) and progress from MMVD to CHF (miR‐181c and miR‐495). Ex‐miRNA expression‐level changes appear to be more specific to disease states than total plasma miRNA.RESPONSIBLE EDITOR Elena Aikawa, Harvard Medical School, USA
VariantTools: an extensible framework for developing and testing variant callers
Authors: Lawrence Michael , Gentleman Robert 
Published: July 2017

Abstract

Motivation
Variant calling is the complex task of separating real polymorphisms from errors. The appropriate strategy will depend on characteristics of the sample, the sequencing methodology and on the questions of interest.

Results
We present VariantTools, an extensible framework for developing and testing variant callers. There are facilities for reproducibly tallying, filtering, flagging and annotating variants. The tools are extensible, modular and flexible, so that they are tunable to particular use cases, and they interoperate with existing analysis software so that they can be embedded in established work flows.

Availability and implementation
VariantTools is available from http://www.bioconductor.org/.

Supplementary information
Supplementary data are available at Bioinformatics online.
Auditory Brainstem Implant Array Position Varies Widely Among Adult and Pediatric Patients and Is Associated With Perception
Authors: Barber Samuel R. , Kozin Elliott D. , Remenschneider Aaron K. , Puram Sidharth V. , Smith Max , Herrmann Barbara S. , Cunnane Mary E. , Brown M. Christian , Lee Daniel J. 
Published: July 2017

Objectives:
The auditory brainstem implant (ABI) provides sound awareness to patients who are ineligible for cochlear implantation. Auditory performance varies widely among similar ABI cohorts. We hypothesize that differences in electrode array position contribute to this variance. Herein, we classify ABI array position based on postoperative imaging and investigate the relationship between position and perception.

Design:
Retrospective review of pediatric and adult ABI users with postoperative computed tomography. To standardize views across subjects, true axial reformatted series of scans were created using the McRae line. Using multiplanar reconstructions, basion and electrode array tip coordinates and array angles from vertical were measured. From a lateral view, array angles (V) were classified into types I to IV, and from posterior view, array angles (T) were classified into types A to D. Array position was further categorized by measuring distance vertical from basion (D1) and lateral from midline (D2). Differences between array classifications were compared with audiometric thresholds, number of active electrodes, and pitch ranking.

Results:
Pediatric (n = 4, 2 with revisions) and adult (n = 7) ABI subjects were included in this study. Subjects had a wide variety of ABI array angles, but most were aimed superiorly and posteriorly (type II, n = 7) from lateral view and upright or medially tilted from posterior view (type A, n = 6). Mean pediatric distances were 8 to 42% smaller than adults for D1 and D2. In subjects with perceptual data, electrical thresholds and the number of active electrodes differed among classification types.

Conclusions:
In this first study to classify ABI electrode array orientation, array position varied widely. This variability may explain differences in auditory performance.
Topical Tacrolimus for Corneal Subepithelial Infiltrates Secondary to Adenoviral Keratoconjunctivitis
Authors: Berisa Prado Silvia , Riestra Ayora Ana C. , Lisa Fernández Carlos , Chacón Rodríguez Manuel , Merayo-Lloves Jesús , Alfonso Sánchez José F. 
Published: July 2017

Purpose:
The objective of this study was to determine the efficacy and safety of topical tacrolimus compounded in the Pharmacy Service for the treatment of subepithelial corneal infiltrates (SEIs) secondary to adenoviral keratoconjunctivitis.

Methods:
This retrospective study included patients who had been dispensed topical tacrolimus for the treatment of SEIs during the previous year. Patients were treated with tacrolimus 0.03% eye drops twice daily or tacrolimus 0.02% ointment once daily. The following data were recorded: length of treatment, visual acuity before and after treatment, intraocular pressure before, during, and at the end of treatment, previous treatments, and the presence of SEIs after treatment. The subjective symptoms of the patients were also assessed.

Results:
Fifty-five patients (85 eyes) were included, 54.5% with bilateral involvement. A total of 31 (36.5%) eyes were treated with tacrolimus ointment and 54 eyes (63.5%) with tacrolimus eye drops. The median length of treatment was 185 days (p25–75: 93.5–426), and the mean follow-up duration was 363 days (p25–75: 148–540). In 62.35% of the eyes, the SEIs were reduced in number and size, and in 31.76%, they were eliminated. The patients had better visual acuity after treatment with highly statistically significant differences. Tolerance was good overall, being better in the eye drops group.

Conclusions:
Topical tacrolimus, compounded in the pharmacy, seems to be an effective and safe alternative for the treatment of SEIs secondary to adenovirus keratoconjunctivitis.
Efficacy of Two Different Liquid Nitrogen Cryotherapy Regimes in the Treatment of Plantar Viral Warts
Authors: Leow Mabel Qi He , Tan Eugene Sern-Ting 
Published: July 2017

ABSTRACT

Aim
The aim of this study was to compare the efficacy and safety of liquid nitrogen cryotherapy using two rounds of 10-second freeze–thaw cycles versus four rounds of 5-second freeze–thaw cycles in the treatment of plantar viral warts.

Methods
A prospective two-group randomized trial was conducted. Subjects in Group A received the regular two rounds of 10-second sustained freeze. Subjects in Group B received four rounds of 5-second sustained freeze. After each treatment, the pain score, pain duration, and occurrence of blistering were recorded. Wart size was measured on the 4th, 8th, and 12th sessions.

Results
Seventy-eight subjects (Group A = 36, Group B = 42) participated in the study. There was no difference in clinical clearance rates, blistering rates, posttreatment pain score, and duration of posttreatment pain between both groups.

Conclusions
There was no difference in efficacy between two rounds of 10-second freeze–thaw cycles and four rounds of 5-second freeze–thaw cycles in cryotherapy for plantar viral warts in our study cohort. Patients who are unable to tolerate long liquid nitrogen spray cycles may be given multiple short cycles instead, without compromise in therapeutic efficacy. There was no difference in pain and blistering for both groups.
Inflammatory and multiple hepatocellular adenoma are associated with a higher BMI
Authors: Bröker Mirelle E.E. , Gaspersz Marcia P. , Klompenhouwer Anne J. , Hansen Bettina E. , Terkivatan Turkan , Taimr Pavel , Dwarkasing Roy , Thomeer Maarten G.J. , de Man Robert A. , IJzermans Jan N.M. 
Published: July 2017

Aim
To identify patient and lesion characteristics associated with the occurrence of single or multiple hepatocellular adenoma (HCA).

Patients and methods
Using a tertiary centre database, we retrospectively collected information on patient and lesion characteristics, management and follow-up of all patients with HCA included between 2001 and 2016. Patients were classified into three groups; patients with a single HCA, 2–9 HCA and at least 10 HCA.

Results
A total of 458 patients were diagnosed with HCA, including 121 (26.4%) with single HCA, 235 (51.3%) with 2–9 HCA and 102 (22.3%) with at least 10 HCA. Significant differences in the mean BMI were found, with the highest BMI in patients with more than 10 HCA (P<0.05). The mean BMI was significantly higher in patients with inflammatory HCA compared with steatotic HCA (31 vs. 26, respectively, P<0.05). Steatotic HCA were more often single lesions (22/55, 40%), whereas patients with inflammatory HCA were often diagnosed with multiple lesions (122/166, 73%).

Conclusion
Our series show a significantly higher BMI and frequency of inflammatory HCA in patients with multiple HCA compared with single HCA.
Effect of a brief motivational intervention in reducing alcohol consumption in the emergency department: a randomized controlled trial
Authors: Diaz Gomez Cristina , Ngantcha Marcus , Le Garjean Nathalie , Brouard Nadine , Lasbleiz Muriel , Perennes Mathieu , Kerdiles François J. , Le Lan Caroline , Moirand Romain , Bellou Abdelouahab 
Published: July 2017

Background
Introduction to alcohol consumption early in life increases the risk of alcohol dependency and hence motivational interventions are needed in young patients visiting the emergency department (ED).

Aim
This study aims to investigate the efficacy of a brief motivational intervention in reducing alcohol consumption among young ED patients.

Patients and methods
This was a blind randomized controlled trial with follow-up at 3 months. Patients were stratified on the basis of age and blood alcohol level of 0.5 g/l or more. A total of 263 patients aged 16–24 were randomized, with 132 patients in the brief motivational intervention group and 131 in the control group, with data collection at 3 months. From September 2011 to July 2012, a psychologist performed the brief motivational intervention 5 days after the patients’ discharge. A phone call was made at 1 and 2 months. The control group received a self-assessment leaflet. The reduction in consumption was determined on the basis of the number of drinks consumed in the last week prior to the survey.

Results
The mean reduction between number of drinks at baseline and number of drinks at 3 months in the control group was 0.3 and that in the intervention group was 0.9. This reduction in alcohol use in the brief motivational intervention group was not significant. The study did not show an association between brief motivational intervention and repeated drunkenness [relative risk (RR): 0.99, 95% confidence interval (CI): 0.79–1.24], alcohol consumption at least once a month (RR: 0.81, 95% CI: 0.31–2.10) and alcohol consumption at least 10 times during the month (RR: 1.1, 95% CI: 0.96–1.26).

Conclusion
We did not observe a significant decrease in alcohol consumption among the youth. Further studies are needed to confirm the positive impact of a brief motivational intervention in the ED.
Safe discharge and outpatient investigation of ureteric colic: a retrospective analysis
Authors: Stewart Michael 
Published: July 2017

Background
Computed tomography of the kidneys, ureters and bladder is the recommended imaging modality for suspected urolithiasis. Early scanning is advised in guidelines, but there is limited published evidence to support this recommendation.

Patients and methods
In a retrospective study, we reviewed patients managed according to a local guideline. Patients without high-risk features were either imaged during their initial visit (if in the daytime) or discharged for outpatient scans. Complications, unplanned returns, final diagnosis, and intervention rates were compared between groups.

Results
Fifty-four patients were scanned during their initial visit and 151 were scanned as an outpatient at a median interval of 10 days. Unplanned return rates were lower in those scanned as outpatients (7.3 vs. 24.1%), with no significant difference in complications (2.0 vs. 3.7%; none leading to permanent harm). Those scanned as outpatients were less likely to have a stone proven by imaging (39.7 vs. 64.8%), but did not have a significantly higher rate of proven alternative diagnosis (9.3 vs. 13.0%).

Conclusion
There is no evidence in this cohort that discharging patients for outpatient imaging is associated with poorer outcomes, provided that an appropriate clinical risk assessment is carried out.
The role of monogenic disease in children with very early onset inflammatory bowel disease
Authors: Kelsen Judith R. , Baldassano Robert N. 
Published: July 2017

Purpose of review
Inflammatory bowel disease (IBD) is a multifactorial disease caused by dysregulated immune responses to commensal or pathogenic intestinal microbes, resulting in chronic intestinal inflammation. Patients diagnosed with IBD occurring before the age of 5 are a unique population, known as very early onset (VEO)-IBD and can be phenotypically and genetically distinct from older-onset IBD. We aim to review the clinical presentation of children with VEO-IBD and recent discoveries that point to genomic drivers of disease that may impact our therapeutic decisions.

Recent findings
VEO-IBD is increasing in incidence and is associated with more severe disease, aggressive progression and poor response to most conventional therapies. This article will review the advances in sequencing technology that have led to identification of novel gene variants associated with disease and potentially new targeted therapeutic options.

Summary
Children with VEO-IBD may present with a different phenotype and more severe disease than older children and adults. Identification of the causal gene or pathways, these children may allow for true precision medicine with targeted therapy and improved disease course.
Intravenous Iron Sucrose for Treatment of Iron Deficiency Anemia in Pediatric Inflammatory Bowel Disease
Authors: Stein Ronen E. , Plantz Kristen , Maxwell Elizabeth C. , Mamula Petar , Baldassano Robert N. 
Published: July 2017

ABSTRACTObjectives:Iron deficiency anemia (IDA) is a common complication of pediatric inflammatory bowel disease (IBD), yet the effectiveness of oral iron supplementation is limited. Intravenous iron sucrose is an effective and safe alternative treatment for IDA in adults with IBD, but its role in the treatment of IDA in pediatric IBD is unclear. The primary aim of this study was to evaluate the use of iron sucrose in pediatric IBD subjects with IDA and determine the clinical response as measured by improvement in hemoglobin concentration. The secondary aim was to describe adverse events associated with iron sucrose use in this cohort.Methods:A retrospective chart review was performed of all pediatric patients with IBD receiving iron sucrose infusions for IDA at a single tertiary care center between 2011 and 2015.Results:Seventy‐two subjects (53 with Crohn disease, 11 with ulcerative colitis, and 8 with IBD‐unclassified) received a total of 273 iron sucrose infusions. Forty‐three subjects qualified for the efficacy analysis. There was a significant increase in hemoglobin over the treatment course, with mean (±SD) hemoglobin increasing from 9.6 ± 1.2 g/dL at baseline to 12.1 ± 1.3 g/dL after iron sucrose treatment (P < 0.001). Eighteen adverse events were reported in 13 subjects (18.1% of subjects and 6.6% of infusions). No anaphylaxis reactions occurred and none of the adverse events were, however, life‐threatening or required hospitalization.Conclusions:Intravenous iron sucrose is a safe and potentially efficacious treatment choice for IDA in pediatric IBD.
The Microbiome in Posttraumatic Stress Disorder and Trauma-Exposed Controls: An Exploratory Study
Authors: Hemmings Sian M.J. , Malan-Müller Stefanie , van den Heuvel Leigh L. , Demmitt Brittany A. , Stanislawski Maggie A. , Smith David G. , Bohr Adam D. , Stamper Christopher E. , Hyde Embriette R. , Morton James T. , Marotz Clarisse A. , Siebler Philip H. , Braspenning Maarten , Van Criekinge Wim , Hoisington Andrew J. , Brenner Lisa A. , Postolache Teodor T. , McQueen Matthew B. , Krauter Kenneth S. , Knight Rob , Seedat Soraya , Lowry Christopher A. 
Published: July 2017

ABSTRACT

Objective
Inadequate immunoregulation and elevated inflammation may be risk factors for posttraumatic stress disorder (PTSD), and microbial inputs are important determinants of immunoregulation; however, the association between the gut microbiota and PTSD is unknown. This study investigated the gut microbiome in a South African sample of PTSD-affected individuals and trauma-exposed (TE) controls to identify potential differences in microbial diversity or microbial community structure.

Methods
The Clinician-Administered PTSD Scale for DSM-5 was used to diagnose PTSD according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. Microbial DNA was extracted from stool samples obtained from 18 individuals with PTSD and 12 TE control participants. Bacterial 16S ribosomal RNA gene V3/V4 amplicons were generated and sequenced. Microbial community structure, α-diversity, and β-diversity were analyzed; random forest analysis was used to identify associations between bacterial taxa and PTSD.

Results
There were no differences between PTSD and TE control groups in α- or β-diversity measures (e.g., α-diversity: Shannon index, t = 0.386, p = .70; β-diversity, on the basis of analysis of similarities: Bray-Curtis test statistic = –0.033, p = .70); however, random forest analysis highlighted three phyla as important to distinguish PTSD status: Actinobacteria, Lentisphaerae, and Verrucomicrobia. Decreased total abundance of these taxa was associated with higher Clinician-Administered PTSD Scale scores (r = –0.387, p = .035).

Conclusions
In this exploratory study, measures of overall microbial diversity were similar among individuals with PTSD and TE controls; however, decreased total abundance of Actinobacteria, Lentisphaerae, and Verrucomicrobia was associated with PTSD status.
Perceived Stress, Depressive Symptoms, and Oxidative DNA Damage
Authors: Shimanoe Chisato , Hara Megumi , Nishida Yuichiro , Nanri Hinako , Horita Mikako , Yamada Yosuke , Li Yun-Shan , Kasai Hiroshi , Kawai Kazuaki , Higaki Yasuki , Tanaka Keitaro 
Published: July 2017

ABSTRACT

Objective
Psychosocial stress may influence the risk of disease through its association with oxidative DNA damage. We examined whether perceived stress and depressive symptoms were associated with urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG), with mutual interaction on 8-OHdG.

Methods
This cross-sectional study included 6517 individuals aged 45 to 74 years who participated, between 2010 and 2012, in a follow-up survey of an ongoing cohort study. Perceived stress during the past year was measured using a self-report questionnaire. Depressive symptoms were evaluated using the Zung Self-Rating Depression Scale. Urinary 8-OHdG concentrations were measured using a column switching high-pressure liquid chromatography system coupled to an electrochemical detector.

Results
Higher perceived stress was significantly associated with higher 8-OHdG (2.1% increase per one-category increase of stress; p
trend = .025), even after adjusting for sex, age, supplement use, psychosocial factors, psychotropic medication use, smoking, and body mass index. This association was modestly attenuated after further adjustment for physical activity, suggesting possible mediation or confounding by this factor. Depressive symptoms were not significantly associated with 8-OHdG. No significant interaction was detected between perceived stress and depressive symptoms on 8-OHdG.

Conclusions
In a general Japanese population, we found a weak positive association between perceived stress and urinary excretion of 8-OHdG, whereas no association was observed between depressive symptoms and 8-OHdG. Further studies are needed to examine whether the association between perceived stress and 8-OHdG is modified by depressive symptoms.
Three- versus four-factor prothrombin complex concentrates for “factor-based” resuscitation in a porcine hemorrhagic shock model
Authors: Moe Donald Michael , Lallemand Michael Scott , McClellan John Mason , Smith Joshua Porter , Marko Shannon T. , Eckert Matthew J. , Martin Matthew J. 
Published: July 2017

BACKGROUND
Bleeding is a leading cause of preventable death after severe injury. Prothrombin complex concentrates (PCC) treat inborn coagulation disorders and reverse oral anticoagulants, but are proposed for use in “factor-based” resuscitation strategies. Few studies exist for this indication in acidosis, or that compare 3-factor PCC (3PCC) versus 4-factor PCC (4PCC) products. We aimed to assess and compare their safety and efficacy in a porcine model of severe hemorrhagic shock and coagulopathy.

METHODS
Twenty-five adult Yorkshire swine underwent 35% volume hemorrhage, ischemia-reperfusion injury, and protocolized crystalloid resuscitation. Seventeen animals were randomized at 4 hours after model creation to receive a 45-IU/kg dose of either 3PCC or 4PCC. An additional eight animals received autologous plasma transfusion before 4PCC to better characterize response to PCC. Individual factor levels were drawn at 4 hours and 6 hours.

RESULTS
The model created significant acidosis with mean pH of 7.21 and lactate of 9.6 mmol/L. After PCC, 66.7% of 3PCC animals and 25% of 4PCC animals (regardless of plasma administration) developed consumptive coagulopathy. The animals that developed consumptive coagulopathy had manifested the “lethal triad” with lower temperatures (36.3°C vs. 37.8°C), increased acidosis (pH, 7.14 vs. 7.27; base excess, −12.1 vs. –6.5 mEq/L), and worse coagulopathy (prothrombin time, 17.1 vs. 14.6 seconds; fibrinogen, 87.9 vs. 124.1 mg/dL) (all p < 0.05). In the absence of a consumptive coagulopathy, 3PCC and 4PCC improved individual clotting factors with transient improvement of prothrombin time, but there was significant depletion of fibrinogen and platelets with no lasting improvement of coagulopathy.

CONCLUSION
PCC failed to correct coagulopathy and was associated with fibrinogen and platelet depletion. Of greater concern, PCC administration resulted in consumptive coagulopathy in the more severely ill animals. The incidence of consumptive coagulopathy was markedly increased with 3PCC versus 4PCC, and these products should be used with caution in this setting.