bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling of Antilatency Treatment in HIV: What Is the Optimal Duration of Antiretroviral Therapy-Free HIV Remission?
Authors: Cromer Deborah , Pinkevych Mykola , Rasmussen Thomas A. , Lewin Sharon R. , Kent Stephen J. , Davenport Miles P. 
Published: October 2017

ABSTRACT
A number of treatment strategies are currently being developed to promote antiretroviral therapy-free HIV cure or remission. While complete elimination of the HIV reservoir would prevent recurrence of infection, it is not clear how different remission lengths would affect viral rebound and transmission. In this work, we use a stochastic model to show that a treatment that achieves a 1-year average time to viral remission will still lead to nearly a quarter of subjects experiencing viral rebound within the first 3 months. Given quarterly viral testing intervals, this leads to an expected 39 (95% uncertainty interval [UI], 22 to 69) heterosexual transmissions and up to 262 (95% UI, 107 to 534) homosexual transmissions per 1,000 treated subjects over a 10-year period. Thus, a balance between high initial treatment levels, risk of recrudescence, and risk of transmission should be considered when assessing the “useful” or optimal length of antiretroviral therapy-free HIV remission to be targeted. We also investigate the trade-off between increasing the average duration of remission versus the risk of treatment failure (viral recrudescence) and the need for retreatment. To minimize drug exposure, we found that the optimal target of antilatency interventions is a 1,700-fold reduction in the size of the reservoir, which leads to an average time to recrudescence of 30 years. Interestingly, this is a significantly lower level of reduction than that required for complete elimination of the viral reservoir. Additionally, we show that when shorter periods are targeted, there is a real probability of viral transmission occurring between tests for viral rebound.

IMPORTANCE
Current treatment of HIV involves patients taking antiretroviral therapy to ensure that the level of virus remains very low or undetectable. Continuous therapy is required, as the virus persists in a latent state within cells, and when therapy is stopped, the virus rebounds, usually within 2 weeks. A major question is how to reduce the amount of persistent virus and therefore allow a delay or remission until the virus returns after ceasing therapy. In this work, we consider the probability that HIV will still rebound even after this reduction and ask what the likelihood of viral transmission would be in this case.
Presence of atopy increases the risk of asthma relapse
Authors: Teoh Laurel , Mackay Ian M , Van Asperen Peter P , Acworth Jason P , Hurwitz Mark , Upham John W , Siew Weng Hou , Wang Claire Y T , Sloots Theo P , Neeman Teresa , Chang Anne B 
Published: October 2017

ObjectivesTo describe the point prevalence of respiratory viruses/atypical bacteria using PCR and evaluate the impact of respiratory viruses/atypical bacteria and atopy on acute severity and clinical recovery in children with hospitalised and non-hospitalised asthma exacerbations.DesignThis was a prospective study performed during 2009–2011.SettingThe study was performed in the emergency departments of two hospitals.Patients244 children aged 2–16 years presenting with acute asthma to the emergency departments were recruited. A nasopharyngeal aspirate and allergen skin prick test were performed.Main outcome measuresThe outcomes were divided into (1) acute severity outcomes (Australian National Asthma Council assessment, hospitalisation, Functional Severity Scale, Acute Asthma Score, asthma quality of life questionnaires for parents (PACQLQ) on presentation, asthma diary scores (ADS) on presentation and length of hospitalisation) and (2) recovery outcomes (PACQLQ for 21 days, ADS for 14 days and representation for asthma for 21 days).ResultsPCR for viruses/atypical bacteria was positive in 81.7% of children (75.1% human rhinovirus, codetection in 14.2%).Mycoplasma pneumoniaeandChlamydophila pneumoniaewere rarely detected. The presence of micro-organisms had little impact on acute asthma or recovery outcomes. Children with atopy were significantly more likely to relapse and represent for medical care by day 14 (OR 1.11, 95% CI 1.00 to 1.23).ConclusionsThe presence of any viruses is associated with asthma exacerbations but does not appear to influence asthma recovery. In contrast, atopy is associated with asthma relapse.M. pneumoniaeandC. pneumoniaeare rare triggers of acute asthma in young children.
Discrepancies between ClinicalTrials.gov recruitment status and actual trial status: a cross-sectional analysis
Authors: Jones Christopher W , Safferman Michelle R , Adams Amanda C , Platts-Mills Timothy F 
Published: October 2017

ObjectivesTo determine the accuracy of the recruitment status listed on ClinicalTrials.gov as compared with the actual trial status.DesignCross-sectional analysis.SettingRandom sample of interventional phase 2–4 clinical trials registered between 2010 and 2012 on ClinicalTrials.gov.Primary outcome measureFor each trial which was listed within ClinicalTrials.gov as ongoing, two investigators performed a comprehensive literature search for evidence that the trial had actually been completed. For each trial listed as completed or terminated early by ClinicalTrials.gov, we compared the date that the trial was actually concluded with the date the registry was updated to reflect the study’s conclusion status.ResultsAmong the 405 included trials, 92 had a registry status indicating that study activity was either ongoing or the recruitment status was unknown. Of these, published results were available for 34 (37%). Among the 313 concluded trials, the median delay between study completion and a registry update reflecting that the study had ended was 141 days (IQR 48–419), with delays of over 1 year present for 29%. In total, 125 trials (31%) either had a listed recruitment status which was incorrect or had a delay of more than 1 year between the time the study was concluded and the time the registry recruitment status was updated.ConclusionsAt present, registry recruitment status information in ClinicalTrials.gov is often outdated or wrong. This inaccuracy has implications for the ability of researchers to identify completed trials and accurately characterise all available medical knowledge on a given subject.
Ectopic pregnancy: exploration of its global research architecture using density-equalising mapping and socioeconomic benchmarks
Authors: Brüggmann Dörthe , Kollascheck Jana , Quarcoo David , Bendels Michael H , Klingelhöfer Doris , Louwen Frank , Jaque Jenny M , Groneberg David A 
Published: October 2017

ObjectiveAbout 2% of all pregnancies are complicated by the implantation of the zygote outside the uterine cavity and termed ectopic pregnancy. Whereas a multitude of guidelines exists and related research is constantly growing, no thorough assessment of the global research architecture has been performed yet. Hence, we aim to assess the associated scientific activities in relation to geographical and chronological developments, existing research networks and socioeconomic parameters.DesignRetrospective, descriptive study.SettingOn the basis of the NewQIS platform, scientometric methods were combined with novel visualising techniques such as density-equalising mapping to assess the scientific output on ectopic pregnancy. Using the Web of Science, we identified all related entries from 1900 to 2012.Results8040 publications were analysed. The USA and the UK were dominating the field in regard to overall research activity (2612 and 723 publications), overall citation numbers and country-specific H-Indices (US: 80, UK: 42). Comparison to economic power of the most productive countries demonstrated that Israel invested more resources in ectopic pregnancy-related research than other nations (853.41 ectopic pregnancy-specific publications per 1000 billlion US$ gross domestic product (GDP)), followed by the UK (269.97). Relation to the GDP per capita index revealed 49.3 ectopic pregnancy-specific publications per US$1000 GDP per capita for the USA in contrast to 17.31 for the UK. Semiqualitative indices such as country-specific citation rates ranked Switzerland first (24.7 citations per ectopic pregnancy-specific publication), followed by the Scandinavian countries Finland and Sweden. Low-income countries did not exhibit significant research activities.ConclusionsThis is the first in-depth analysis of global ectopic pregnancy research since 1900. It offers unique insights into the global scientific landscape. Besides the USA and the UK, Scandinavian countries and Switzerland can also be regarded as leading nations with regard to their relative socioeconomic input.
Protocol for a pilot, randomised, double-blinded, placebo-controlled trial of prophylactic use of tranexamic acid for preventing postpartum haemorrhage (TAPPH-1)
Authors: Alam Asim , Bopardikar Ameya , Au Shelly , Barrett Jon , Callum Jeannie , Kiss Alex , Choi Stephen 
Published: October 2017

IntroductionPostpartum haemorrhage (PPH) is the leading cause of maternal morbidity and mortality worldwide. Despite the availability of multiple uterotonic agents, the incidence of PPH continues to rise. Tranexamic acid (TXA) has been shown to be a safe, effective and inexpensive therapeutic option for the treatment of PPH, however, its use prophylactically in mitigating the risk of PPH is unknown. This pragmatic randomised prospective trial assesses the feasibility and safety of administering TXA at the time of delivery for the prevention of PPH.Methods and analysisA pilot pragmatic randomised double-blinded placebo-controlled trial will be performed. 58 singleton parturients at term >32 weeks, undergoing either spontaneous vaginal delivery, or caesarean section will be randomised to receive 1 g of TXA or placebo (0.9% saline) intravenously. The primary outcome assessed will be the feasibility of administrating TXA, along with collecting data regarding safety of drug administration. The groups will also be analysed on efficacy of mitigating the onset of PPH and clinically relevant variables. Demographic, feasibility, safety and clinical endpoints will be summarised and the appropriate measures of central tendency and dispersion will be presented.Ethics and disseminationThis protocol was approved by the Sunnybrook Health Sciences Centre Research Ethics Board (number: 418-2016). The results will be disseminated in a peer-reviewed journal and at scientific meetings.Trial registration numberNCT03069859; Pre-results.
Predicting the Functional Impact of KCNQ1 Variants of Unknown Significance
Authors: Li Bian , Mendenhall Jeffrey L. , Kroncke Brett M. , Taylor Keenan C. , Huang Hui , Smith Derek K. , Vanoye Carlos G. , Blume Jeffrey D. , George Alfred L. , Sanders Charles R. , Meiler Jens 
Published: October 2017

Background—
An emerging standard-of-care for long-QT syndrome uses clinical genetic testing to identify genetic variants of the KCNQ1 potassium channel. However, interpreting results from genetic testing is confounded by the presence of variants of unknown significance for which there is inadequate evidence of pathogenicity.

Methods and Results—

In this study, we curated from the literature a high-quality set of 107 functionally characterized KCNQ1 variants. Based on this data set, we completed a detailed quantitative analysis on the sequence conservation patterns of subdomains of KCNQ1 and the distribution of pathogenic variants therein. We found that conserved subdomains generally are critical for channel function and are enriched with dysfunctional variants. Using this experimentally validated data set, we trained a neural network, designated Q1VarPred, specifically for predicting the functional impact of KCNQ1 variants of unknown significance. The estimated predictive performance of Q1VarPred in terms of Matthew’s correlation coefficient and area under the receiver operating characteristic curve were 0.581 and 0.884, respectively, superior to the performance of 8 previous methods tested in parallel. Q1VarPred is publicly available as a web server at
http://meilerlab.org/q1varpred
.

Conclusions—
Although a plethora of tools are available for making pathogenicity predictions over a genome-wide scale, previous tools fail to perform in a robust manner when applied to KCNQ1. The contrasting and favorable results for Q1VarPred suggest a promising approach, where a machine-learning algorithm is tailored to a specific protein target and trained with a functionally validated data set to calibrate informatics tools.
Characterization of a Human Induced Pluripotent Stem Cell–Derived Cardiomyocyte Model for the Study of Variant Pathogenicity
Authors: Gélinas Roselle , El Khoury Nabil , Chaix Marie-A. , Beauchamp Claudine , Alikashani Azadeh , Ethier Nathalie , Boucher Gabrielle , Villeneuve Louis , Robb Laura , Latour Frédéric , Mondesert Blandine , Rivard Lena , Goyette Philippe , Talajic Mario , Fiset Céline , Rioux John David 
Published: October 2017

Background—
Long-QT syndrome is a potentially fatal condition for which 30% of patients are without a genetically confirmed diagnosis. Rapid identification of causal mutations is thus a priority to avoid at-risk situations that can lead to fatal cardiac events. Massively parallel sequencing technologies are useful for the identification of sequence variants; however, electrophysiological testing of newly identified variants is crucial to demonstrate causality. Long-QT syndrome could, therefore, benefit from having a standardized platform for functional characterization of candidate variants in the physiological context of human cardiomyocytes.

Methods and Results—
Using a variant in Kir2.1 (Gly52Val) revealed by whole-exome sequencing in a patient presenting with symptoms of long-QT syndrome as a proof of principle, we demonstrated that commercially available human induced pluripotent stem cell–derived cardiomyocytes are a powerful model for screening variants involved in genetic cardiac diseases. Immunohistochemistry experiments and whole-cell current recordings in human embryonic kidney cells expressing the wild-type or the mutant Kir2.1 demonstrated that Kir2.1-52V alters channel cellular trafficking and fails to form a functional channel. Using human induced pluripotent stem cell–derived cardiomyocytes, we not only confirmed these results but also further demonstrated that Kir2.1-52V is associated with a dramatic prolongation of action potential duration with evidence of arrhythmic activity, parameters which could not have been studied using human embryonic kidney cells.

Conclusions—
Our study confirms the pathogenicity of Kir2.1-52V in 1 patient with long-QT syndrome and also supports the use of isogenic human induced pluripotent stem cell–derived cardiomyocytes as a physiologically relevant model for the screening of variants of unknown function.
Risk Stratification of Severe Aortic Stenosis With Preserved Left Ventricular Ejection Fraction Using Peak Aortic Jet Velocity
Authors: Bohbot Yohann , Rusinaru Dan , Delpierre Quentin , Marechaux Sylvestre , Tribouilloy Christophe 
Published: October 2017

Background—
Current guidelines consider aortic valve replacement reasonable in asymptomatic patients with very severe aortic stenosis (AS); however, the definition of very severe AS based on peak aortic jet velocity (Vmax) remains unclear with a 5-m/s cutoff in US guidelines and 5.5 m/s in European guidelines. Because ≈20% of patients with severe AS and preserved left ventricular ejection fraction have Vmax in this range, we aimed to assess the relationship between Vmax and mortality and determine the best threshold to define very severe AS.

Methods and Results—

A total of 1140 patients with severe AS (aortic valve area ≤1 cm
2
, Vmax ≥4 m/s) and preserved left ventricular ejection fraction were included. The population was divided into 4 groups according to Vmax (4–4.49, 4.5–4.99, 5–5.49, and ≥5.5 m/s). After adjustment for covariates (including surgery), there was no difference in all-cause mortality between Vmax 4 to 4.49 m/s and Vmax 4.5 to 4.99 m/s (
P
=0.64). Both Vmax 5 to 5.49 m/s and Vmax ≥5.5 m/s exhibited significant excess mortality compared with Vmax 4 to 4.49 m/s (adjusted hazard ratio=1.34 [1.18–1.52];
P
<0.001, and 1.28 [1.16–1.41];
P
<0.001, respectively). Mortality risk was similar for Vmax 5 to 5.49 m/s and Vmax ≥5.5 m/s (
P
=0.93). Compared with Vmax <5 m/s, patients with Vmax ≥5 m/s had greater mortality risk (adjusted hazard ratio=1.86 [1.55–2.54];
P
<0.001), even in the subgroup of asymptomatic even in the subgroup of asymptomatic patients (adjusted hazard ratio=2.08 [1.25-3.46];
P
=0.005).

Conclusions—
Our results demonstrate the strong relationship between Vmax and mortality in patients with severe AS and preserved left ventricular ejection fraction irrespective of symptoms. Vmax ≥5 m/s at the time of AS diagnosis identifies patients with very severe AS at high risk of death.
Tai Chi Is a Promising Exercise Option for Patients With Coronary Heart Disease Declining Cardiac Rehabilitation
Authors: Salmoirago‐Blotcher Elena , Wayne Peter M. , Dunsiger Shira , Krol Julie , Breault Christopher , Bock Beth C. , Wu Wen‐Chih , Yeh Gloria Y. 
Published: October 2017

Background

More than 60% of patients decline participation in cardiac rehabilitation after a myocardial infarction. Options to improve physical activity (
PA
) and other risk factors in these high‐risk individuals are limited. We conducted a phase 2 randomized controlled trial to determine feasibility, safety, acceptability, and estimates of effect of tai chi on
PA
, fitness, weight, and quality of life.

Methods and Results

Patients with coronary heart disease declining cardiac rehabilitation enrollment were randomized to a “
LITE
” (2 sessions/week for 12 weeks) or to a “
PLUS
” (3 sessions/week for 12 weeks, then maintenance classes for 12 additional weeks) condition.
PA
(accelerometry), weight, and quality of life (Health Survey Short Form) were measured at baseline and 3, 6, and 9 months after baseline; aerobic fitness (stress test) was measured at 3 months. Twenty‐nine participants (13
PLUS
and 16
LITE
) were enrolled. Retention at 9 months was 90% (
LITE
) and 88% (
PLUS
). No serious tai chi–related adverse events occurred. Significant mean between group differences in favor of the
PLUS
group were observed at 3 and 6 months for moderate‐to‐vigorous
PA
(100.33 min/week [95% confidence interval, 15.70–184.95 min/week] and 111.62 min/week; [95% confidence interval, 26.17–197.07 min/week], respectively, with a trend toward significance at 9 months), percentage change in weight, and quality of life. No changes in aerobic fitness were observed within and between groups.

Conclusions

In this community sample of patients with coronary heart disease declining enrollment in cardiac rehabilitation, a 6‐month tai chi program was safe and improved
PA
, weight, and quality of life compared with a 3‐month intervention. Tai chi could be an effective option to improve PA in this high‐risk population.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
02165254.
Economic Impact of Subsequent Depression in Patients With a New Diagnosis of Stable Angina: A Population‐Based Study
Authors: Szpakowski Natalie , Qiu Feng , Masih Shannon , Kurdyak Paul , Wijeysundera Harindra C. 
Published: October 2017

Background
Depression is strongly linked to increased morbidity and mortality in patients with chronic stable angina; however, its associated healthcare costs have been less well studied. Our objective was to identify the characteristics of chronic stable patients found to have depression and to determine the impact of an occurrence of depression on healthcare costs within 1 year of a diagnosis of stable angina.

Methods and Results
In this population‐based study conducted in Ontario, Canada, we identified patients diagnosed with stable angina based on angiogram between October 1, 2008, and September 30, 2013. Depression was ascertained by physician billing codes and hospital admission diagnostic codes contained within administrative databases. The primary outcome was cumulative mean 1‐year healthcare costs following index angiogram. Generalized linear models were developed with a logarithmic link and γ distribution to determine predictors of cost. Our cohort included 22 917 patients with chronic stable angina. Patients with depression had significantly higher mean 1‐year healthcare costs ($32 072±$41 963) than patients without depression ($23 021±$25 741). After adjustment for baseline comorbidities, depression was found to be a significant independent predictor of cost, with a cost ratio of 1.33 (95% confidence interval, 1.29–1.37). Higher costs in depressed patients were seen in all healthcare sectors, including acute and ambulatory care.

Conclusions
Depression is an important driver of healthcare costs in patients following a diagnosis of chronic stable angina. Further research is needed to understand whether improvements in the approach to diagnosis and treatment of depression will translate to reduced expenditures in this population.
Quantifying the Effects of Horizontal Grid Length and Parameterized Convection on the Degree of Convective Organization Using a Metric of the Potential for Convective Interaction
Authors: White B. A. , Buchanan A. M. , Birch C. E. , Stier P. , Pearson K. J. 
Published: October 2017

Abstract
The organization of deep convection and its misrepresentation in many global models is the focus of much current interest. A new method is presented for quantifying convective organization based on the identification of convective objects and subsequent derivation of object numbers, areas, and separation distances to describe the degree of convective organization. These parameters are combined into a “convection organization potential” based on the physical principle of an interaction potential between pairs of convective objects. This technique is applied to simulated and observed fields of outgoing longwave radiation (OLR) over the West African monsoon region using data from Met Office Unified Model simulations and satellite observations made by the Geostationary Earth Radiation Budget (GERB) instrument. The method is evaluated by using it to quantify differences between models with different horizontal grid lengths and representations of convection. Distributions of OLR, precipitation and organization parameters, the diurnal cycle of convection, and relationships between the meteorology in different states of organization are compared. Switching from a configuration with parameterized convection to one that allows the model to resolve convective processes at the model grid scale is the leading-order factor improving some aspects of model performance, while increased model resolution is the dominant factor for others. However, no single model configuration performs best compared to observations, indicating underlying deficiencies in both model scaling and process understanding.