bluuebunny/crossref_metadata_2025_split huggingface dataset:
P2832Outcomes of catheter ablation for atrial fibrillation based on sex: data from the cabana trial
Authors: Poole J , Russo A M , Cha Y M , Monahan K H , Al-Khalidi H R , Silverstein A P , Bahnson T D , Mark D B , Lee K L , Packer D L 
Published: October 2019

Abstract

Background
Sex-specific outcomes may differ amongst patients receiving catheter ablation for atrial fibrillation (AF).

Purpose
Assess sex-specific outcomes in the patients randomized to catheter ablation or drug therapy in CABANA.

Methods
CABANA randomized 2204 pts with AF to catheter ablation or drug therapy (rate/rhythm-control). The outcomes of combined death, disabling stroke, severe bleeding, or cardiac arrest (intention to treat-ITT) or all-cause death were not different. But, ablation significantly improved combined death or CV hospitalization. This analysis compares clinical characteristics by sex and determines sex-specific hazard ratios based on a comparison of ablation vs drug therapy.

Results
Females were 37.3% of ablation and 37.0% of drug therapy patients. Females were older, more often white race, had less CAD, or sleep apnea, but had higher NYHA Class, higher CHA2DS2VASc, and more often had paroxysmal (v. persistent) AF, and prior AF hospitalization. (Table) HTN, CVA and diabetes were the same (Table).
For the CABANA primary endpoint, an ITT comparison of ablation vs. drug therapy, showed a female hazard ratio (HR) of 1.14 (95% confidence interval (CI) 0.70–1.86), and a male HR of 0.74, (95% CI 0.52–1.06). For all-cause mortality, the female HR was 0.75 (95% CI 0.41–1.40) and male HR was 0.91 (95% CI 0.59–1.40) and for all-cause mortality or CV hospitalization, the female HR was 0.90 (95% CI 0.75–1.09) and male HR was 0.79 (95% CI 0.69–0.92). All interaction p values were non-significant.
Recurrent AF (post 90-day blanking) was significantly reduced for both females and males: female HR 0.64 (95% CI 0.51–0.82), male HR 0.46 95% CI 0.39–0.56), p=0.035
Clinical Characteristics and Outcomes Baseline Characteristics Female (N=818) Male (N=1385) p-value Age: Median (Q1, Q3) 69 (65, 74) 66 (60, 71) <0.001 White 766 (93.9%) 1259 (91.0%) 0.015 CAD 92 (11.2%) 332 (24.0%) <0.001 NYHA ≥II 345 (42.4%) 433 (31.5%) <0.001 Sleep apnea 136 (16.6%) 372 (26.9%) <0.001 CHA2DS2-VASc: Median (Q1, Q3) 3 (3, 4) 2 (1, 3) <0.001 Paroxysmal AF 406 (49.6%) 540 (39.0%) <0.001 Persistent AF 412 (50.4%) 845 (61.0%) AF Hospitalization 353 (43.2%) 521 (37.7%) 0.011

Conclusion
Significant sex-specific outcomes differences were not observed. Sex should not be used as a determining factor in selecting patients for AF therapy.

Acknowledgement/Funding
NIH, St Jude Medical Foundation and Corporation, Biosense Webster Inc., Medtronic Corporation, and Boston Scientific Corporation
P2864A novel mechanism of sinus node dysfunction: intergenic deletion between PITX2 and ANK2 disrupts chromatin structure in pacemaker cell differentiation
Authors: Murata H , Lindenbaum P , Le Scouarnec S , Baron E , Rajalu A , Kyndt F , Deleuze J F , Le Marec H , Probst V , Shimizu W , Redon R , Schott J J 
Published: October 2019

Abstract

Background
Genetics of sinus node dysfunction (SND) remains poorly understood with few genes identified (HCN4, SCN5A, GJA5, KCNQ1, MYH6 and ANK2) and further genetic heterogeneity.

Purpose
We report two families with SND segregating with an intergenic deletion associated with long-range cis-regulatory elements (CREs) of PITX2.

Methods
We applied 30x whole genome sequencing (WGS) to two French families in which exome sequencing did not allow to detect the causing genes of SND and analyzed them bioinformatically.

Results
We first applied WGS to a 4-generation family presenting 16 patients with SND, atrial fibrillation and/or repolarization abnormalities and identified a 15-Kb deletion within a 16.5-cM linkage interval (Zmax = 5.9, θ = 0) on chromosome 4q25. We also applied WGS on a second family presenting 5 patients with SND and identified a 91-Kb deletion overlapping the initial deletion. This intergenic deletion, which was located between PITX2 and ANK2 and contained a binding motif of CCCTC-binding factor (CTCF), was segregating in all patients and was not found in 855 French control genomes. CTCF functions as a genome organizer mediating genomic interactions between genes and CREs. To clarify a possible regulatory function of the 1.5-Mb intergenic region containing the deletion, we interrogated 3 epigenetic databases. High-throughput chromosome conformation capture (Hi-C) (1) revealed that this intergenic region was placed in a topologically associating domain (TAD) containing PITX2. Chromatin interaction analysis by paired-end tag (ChIA-PET) of CTCF (2) suggested several possible functional chromatin loops in the TAD. Of them, a CTCF-mediated chromatin loop corresponding to a 300-Kb genomic region was clarified as a possible CRE using histone modification data from Roadmap. The region ranging between the intra-deletion CTCF motif and another distal motif was repressed in H3K27me3 profiles of fetal heart, while the region was activated in H3K27ac profiles of H1 ESC-derived mesendoderm.

Conclusion
This CRE may regulate expression of PITX2 and/or ANK2 in pacemaker cell differentiation. Ongoing experiments on patient's iPSC and transgenic mouse will further characterize the disease mechanism.
P2867Vildagliptin reduces inducibility of atrial fibrillation in hypertensive rats complicated with diabetes mellitus
Authors: Soeki T , Matsumoto K , Fukuda D , Uematsu E , Matsuura T , Tobiume T , Kusunose K , Ise T , Yamaguchi K , Yagi S , Yamada H , Wakatsuki T , Sata M 
Published: October 2019

Abstract

Background
Atrial fibrillation (AF) is the most common arrhythmia in clinical practice, increasing the incidence of ischemic stroke. Diabetes mellitus (DM) is a predictor of stroke and thromboembolism, and it was reported to be an independent risk factor for AF. A recent study has shown that, in obese mice with diabetes, dipeptidyl peptidase-4 (DPP-4) inhibitor prevents myocardial fibrosis, active oxygen stress, weight loss and improves myocardial hypertrophy. However, the effects of DPP-4 inhibitors on atrial remodeling associated with diabetes and atrial fibrillation have not yet been clarified.

Purpose
This study was performed to assess whether a DPP-4 inhibitor (vildagliptin) ameliorates atrial remodeling in spontaneously hypertensive rats (SHR) with streptozotocin-induced diabetes.

Methods
Rats were divided into 3 groups: SHR without DM, SHR with DM treated with vehicle and SHR-DM treated with vildagliptin (3mg/kg/day; intragastric gavage). For each group, blood pressure, blood glucose level and body weight were measured serially. Cardiac function was also evaluated by echocardiography. Then, we examined AF inducibility by intracardiac electrophysiological study and the inflammation-induced atrial remodeling by biochemical analysis after 4 weeks of treatment.

Results
There was no significant difference in blood pressure and blood gucose level between vehicle and vildagliptin groups. Administration of vildagliptin significantly reduced AF inducibility compared with rats with vehicle. In DM rats treated with vehicle, rapid atrial pacing promoted the gene expression of inflammatory and fibrosis-related biomarkers (TNF-α, MCP-1, collagen-1) in atrium. Vildagliptin reduced these gene expression levels. In addition, administration of vildagliptin significantly reduced the interstitial fibrosis in atrium.

Conclusions
DPP-4 inhibitor, vildagliptin. could prevent atrial inflammation and reduce the AF inducibility in SHR complicated with DM.
P2877The incidence, predictors, and long-term outcomes of new-onset ventricular tachycardia after cardiac surgery
Authors: Choi K.-J , Cho M S , Do U , Kim J , Nam G B , Kim Y H 
Published: October 2019

Abstract

Background
Incidence and outcomes of new-onset ventricular tachycardia (VT) after cardiac surgery are not fully evaluated.

Purpose
We retrospectively analyzed the occurrence of new-onset VTs after cardiac surgery, and their implications on short and long-term mortality.

Methods
Data of 11,004 adult patients who underwent cardiac surgery at our center from 2006 to 2016 were analyzed. VT was diagnosed when 3 or more consecutive wide QRS complexes (>100 bpm) were documented on ECG. The major study outcomes were in-hospital and 5-years overall mortality rates.

Results
During index hospitalization for cardiac surgery, clinical VTs were documented in 184 patients (1.7%), which included 74 sustained VTs (SusVT, ≥30 seconds) and 110 non-sustained VTs (NSVT). Those patients with SusVT and NSVT showed higher in-hospital mortality compared to those without VTs (31.1% vs. 24.5% vs. 2.0% for SusVT, NSVT, and no VT, respectively, P<0.001). During follow-up after discharge from index hospitalization, patients with SusVT showed higher 5-years mortality than those without VTs, while patients with NSVT did not showed significant differences (22.0% vs. 11.7% vs. 9.2%, P<0.001). In the subgroup of patients with sustained VT who were discharged from index hospitalization (n=51), those with recurrent VTs (>24 hours apart from initial episode) were at higher 5-years mortality rate compared to those without (40.7% vs. 15.8%, P=0.018).

Conclusion
Patients with SusVT and NSVT were at higher risk of in-hospital mortality, and patients with SusVT were associated with higher risk of long-term mortality. The mortality risk was even higher in those with recurrent episodes of VTs.

Acknowledgement/Funding
None
Loneliness Increases the Risk of All-Cause Dementia and Alzheimer’s Disease
Authors: Sundström Anna , Adolfsson Annelie Nordin , Nordin Maria , Adolfsson Rolf 
Published: October 2019

Abstract

Objectives
To examine the effect of perceived loneliness on the development of dementia (all-cause), Alzheimer´s disease (AD), and vascular dementia (VaD).

Method
The study comprised 1,905 nondemented participants at baseline, drawn from the longitudinal Betula study in Sweden, with a follow-up time of up to 20 years (mean 11.1 years). Loneliness was measured with a single question: “Do you often feel lonely?”.

Results
During the follow-up, 428 developed dementia; 221 had AD, 157 had VaD, and 50 had dementia of other subtypes. The entire dementia group is denoted “all-cause dementia.” Cox regression models, adjusted for age, gender, and a baseline report of perceived loneliness, showed increased risk of all-cause dementia (hazard ratio [HR] = 1.46, 95% confidence interval [CI] 1.14–1.89), and AD (HR = 1.69, 95% CI 1.20–2.37), but not VaD (HR = 1.34, 95% CI 0.87–2.08). After adjusting for a range of potential confounders, and excluding participants with dementia onset within the first 5 years of baseline (to consider the possibility of reverse causality), the increased risk for the development of all-cause dementia and AD still remained significant (HR = 1.51, 95% CI 1.01–2.25 for all-cause dementia; HR = 2.50, 95% CI 1.44–4.36 for AD).

Discussion
The results suggest that perceived loneliness is an important risk factor for all-cause dementia and especially for AD, but not for VaD. These results underscore the importance of paying attention to subjective reports of loneliness among the elderly adults and identifying potential intervention strategies that can reduce loneliness.
The role of microRNAs in ovarian function and the transition toward novel therapeutic strategies in fertility preservation: from bench to future clinical application
Authors: Alexandri C , Daniel A , Bruylants G , Demeestere I 
Published: October 2019

AbstractBACKGROUNDNew therapeutic approaches in oncology have converted cancer from a certain death sentence to a chronic disease. However, there are still challenges to be overcome regarding the off-target toxicity of many of these treatments. Oncological therapies can lead to future infertility in women. Given this negative impact on long-term quality of life, fertility preservation is highly recommended. While gamete and ovarian tissue cryopreservation are the usual methods offered, new pharmacological-based options aiming to reduce ovarian damage during oncological treatment are very attractive. In this vein, advances in the field of transcriptomics and epigenomics have brought small noncoding RNAs, called microRNAs (miRNAs), into the spotlight in oncology. MicroRNAs also play a key role in follicle development as regulators of follicular growth, atresia and steroidogenesis. They are also involved in DNA damage repair responses and they can themselves be modulated during chemotherapy. For these reasons, miRNAs may be an interesting target to develop new protective therapies during oncological treatment. This review summarizes the physiological role of miRNAs in reproduction. Considering recently developed strategies based on miRNA therapy in oncology, we highlight their potential interest as a target in fertility preservation and propose future strategies to make the transition from bench to clinic.OBJECTIVE AND RATIONALEHow can miRNA therapeutic approaches be used to develop new adjuvant protective therapies to reduce the ovarian damage caused by cytotoxic oncological treatments?SEARCH METHODSA systematic search of English language literature using PubMed and Google Scholar databases was performed through to 2019 describing the role of miRNAs in the ovary and their use for diagnosis and targeted therapy in oncology. Personal data illustrate miRNA therapeutic strategies to target the gonads and reduce chemotherapy-induced follicular damage.OUTCOMESThis review outlines the importance of miRNAs as gene regulators and emphasizes the fact that insights in oncology can inspire new adjuvant strategies in the field of onco-fertility. Recent improvements in nanotechnology offer the opportunity for drug development using next-generation miRNA-nanocarriers.WIDER IMPLICATIONSAlthough there are still some barriers regarding the immunogenicity and toxicity of these treatments and there is still room for improvement concerning the specific delivery of miRNAs into the ovaries, we believe that, in the future, miRNAs can be developed as powerful and non-invasive tools for fertility preservation.
Forest loss shapes the landscape suitability of Kyasanur Forest disease in the biodiversity hotspots of the Western Ghats, India
Authors: Walsh Michael G , Mor Siobhan M , Maity Hindol , Hossain Shah 
Published: October 2019

Abstract

Background
Anthropogenic pressure in biodiversity hotspots is increasingly recognized as a major driver of the spillover and expansion of zoonotic disease. In the Western Ghats region of India, a devastating tick-borne zoonosis, Kyasanur Forest disease (KFD), has been expanding rapidly beyond its endemic range in recent decades. It has been suggested that anthropogenic pressure in the form of land use changes that lead to the loss of native forest may be directly contributing to the expanding range of KFD, but clear evidence has not yet established the association between forest loss and KFD risk.

Methods
The current study sought to investigate the relationship between KFD landscape suitability and both forest loss and mammalian species richness, to inform its epidemiology and infection ecology. A total of 47 outbreaks of KFD between 1 January 2012 and 30 June 2019 were modelled as an inhomogeneous Poisson process.

Results
Both forest loss [relative risk (RR) = 1.83; 95% confidence interval (CI) 1.33–2.51] and mammalian species richness (RR = 1.29; 95% CI 1.16–1.42) were strongly associated with increased risk of KFD and dominated its landscape suitability.

Conclusions
These results provide the first evidence of a clear association between increasing forest loss and risk for KFD. Moreover, the findings also highlight the importance of forest loss in areas of high biodiversity. Therefore, this evidence provides strong support for integrative approaches to public health which incorporate conservation strategies simultaneously protective of humans, animals and the environment.
Reflection and transmission of high-frequency acoustic, electromagnetic and elastic waves at a distinguished class of irregular, curved boundaries
Authors: Radjen Anthony , Gradoni Gabriele , Tew Richard 
Published: October 2019

AbstractReflection and transmission phenomena associated with high-frequency linear wave incidence on irregular boundaries between adjacent acoustic or electromagnetic media, or upon the irregular free surface of a semi-infinite elastic solid, are studied in two dimensions. Here, an ‘irregular’ boundary is one for which small-scale undulations of an arbitrary profile are superimposed upon an underlying, smooth curve (which also has an arbitrary profile), with the length scale of the perturbation being prescribed in terms of a certain inverse power of the large wave-number of the incoming wave field. Whether or not the incident field has planar or cylindrical wave-fronts, the associated phase in both cases is linear in the wave-number, but the presence of the boundary irregularity implies the necessity of extra terms, involving fractional powers of the wave-number in the phase of the reflected and transmitted fields. It turns out that there is a unique perturbation scaling for which precisely one extra term in the phase is needed and hence for which a description in terms of a Friedlander–Keller ray expansion in the form as originally presented is appropriate, and these define a ‘distinguished’ class of perturbed boundaries and are the subject of the current paper.
Design and Analysis of Elimination Surveys for Neglected Tropical Diseases
Authors: Fronterre Claudio , Amoah Benjamin , Giorgi Emanuele , Stanton Michelle C , Diggle Peter J 
Published: October 2019

Abstract
As neglected tropical diseases approach elimination status, there is a need to develop efficient sampling strategies for confirmation (or not) that elimination criteria have been met. This is an inherently difficult task because the relative precision of a prevalence estimate deteriorates as prevalence decreases, and classic survey sampling strategies based on random sampling therefore require increasingly large sample sizes. More efficient strategies for survey design and analysis can be obtained by exploiting any spatial correlation in prevalence within a model-based geostatistics framework. This framework can be used for constructing predictive probability maps that can inform in-country decision makers of the likelihood that their elimination target has been met, and where to invest in additional sampling. We evaluated our methodology using a case study of lymphatic filariasis in Ghana, demonstrating that a geostatistical approach outperforms approaches currently used to determine an evaluation unit’s elimination status.
Human Papillomavirus Vaccine Effectiveness Against HPV Infection: Evaluation of One, Two, and Three Doses
Authors: Markowitz Lauri E , Naleway Allison L , Klein Nicola P , Lewis Rayleen M , Crane Brad , Querec Troy D , Hsiao Amber , Aukes Laurie , Timbol Julius , Weinmann Sheila , Liu Gui , Steinau Martin , Unger Elizabeth R 
Published: October 2019

Abstract

Background
Highly effective human papillomavirus (HPV) vaccines are used in many national programs in 3- or 2-dose schedules. We examined HPV vaccine effectiveness against HPV prevalence by number of doses.

Methods
We collected residual liquid-based cytology samples from US women aged 20–29 years who were screened for cervical cancer. Women continuously enrolled from 2006 through the specimen collection date were analyzed. Specimens were tested using the Linear Array assay. We analyzed prevalence of quadrivalent HPV vaccine (4vHPV) types (HPV 6,11,16,18) and other HPV-type categories and determined prevalence ratios (PRs) and 95% confidence intervals (CIs) for 1, 2, and 3 compared with no vaccine doses.

Results
Among 4269 women, 1052 (24.6%) were unvaccinated, 2610 (61.1%) received 3 doses, 304 (7.1%) received 2 doses, and 303 (7.1%) received 1 dose. The 4vHPV-type prevalence was 7.4% among unvaccinated women compared with 1.7%, 1.0%, and 1.0% among 1-, 2-, and 3-dose recipients. Among women vaccinated at ≤18 years, adjusted PRs for 1, 2, and 3 doses were 0.06 (95% CI, 0.01–0.42), 0.05 (95% CI, 0.01–0.39), and 0.06 (95% CI, 0.04–0.12).

Conclusions
Among women who received their first dose at age ≤18, estimated HPV vaccine effectiveness was high regardless of number of doses.
Positional variation rather than salt stress dominates changes in three-dimensional leaf shape patterns in cucumber canopies
Authors: Schmidt Dominik , Kahlen Katrin 
Published: October 2019

Abstract
Leaf shape plays a key role in the interaction of a plant with its environment, best-known in the plant’s light harvest. Eﬀects of the environment on the interplay of canopy architecture and physiological functioning can be estimated using functional-structural plant models (FSPMs). In order to reduce the complexity of canopy simulations, leaf shape models used in FSPMs are often simple prototypes scaled to match current leaf area. L-Cucumber is such an FSPM, whose leaf prototype mimics average real leaf shape of unstressed cucumber plants well. However, adaptation processes or stress responses may lead to non-proportional changes in leaf geometries, which, for example, could aﬀect length to width ratios or curvatures. The current leaf shape model in L-Cucumber is static and hence does not incorporate changes in leaf shape within or between plants. Thus, the aim of this study was to estimate leaf shape variation and exemplarily study its eﬀects on FSPM simulations. Three-dimensional leaf coordinate data from a salt stress study were analysed with a robust Bayesian mixed-eﬀects model for estimating leaf shape depending on rank, size and salinity. Results showed that positional and size variation rather than salinity levels dominated 3D leaf shape patterns of cucumber. Considering variable leaf shapes in relation to this main sources of variation in L-Cucumber simulations, only minor eﬀects compared to a realistic, yet static average shape were found. However, with similar computational demands variation in shapes other studies highly sensitive to shape dynamics, for example, pesticide spraying might be aﬀected more strongly.
Improved Intraoperative Hemodynamics in Burn Surgery: An Institutional Change to Pediatric-Specific Hemostasis Solutions
Authors: Lawrence Marley B , Keil Dayley S , Maves Gregory S , Chen Fei , Jones Samuel W , Baboolal Hemanth A 
Published: October 2019

Abstract
A cornerstone of burn surgery hemostasis is infiltration of tumescent vasopressor solutions and topical vasoconstrictor-soaked compresses. Studies detailing pediatric-specific concentrations of these solutions are lacking. Our aim was to assess hemodynamic changes after an institutional change in tumescent vasopressor solution and vasopressor-soaked topical compresses for hemostasis management during pediatric burn surgery. Once the institutional change was implemented, cases performed before and after the intervention were reviewed; inclusion criteria included age 0-18 years, burn total body surface area (TBSA) ≥ 10%, and surgery length >50 minutes. Primary outcomes included changes in intraoperative mean arterial pressure, maximum inhaled anesthetic concentration, need for direct acting vasodilators, estimated blood loss and need for blood transfusions. 30 patients were included in the intervention group, and 31 in the control group. There was a significant difference in peak intraoperative blood pressure in the intervention group (21.4%) compared to the control group (48.0%, p=0.005). Maximum inhaled anesthetic concentrations were lower in the intervention group (2.5% versus 2.8%, p=0.02). Estimated blood loss per TBSA decreased significantly (8.2 mL/1% TBSA versus 1.7, p=0.008), as well as blood transfusion rates, with a transfusion rate of 16.7% in the intervention group versus 45.2% in the control group (p=0.03). The changes instituted in type and concentration of tumescent solution and vasopressor-soaked topical compresses were associated with improved hemodynamic changes and decreased transfusion rates intraoperatively.