bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineering New Approaches to Cancer Vaccines
Authors: Mehta Naveen K. , Moynihan Kelly D. , Irvine Darrell J. 
Published: July 2015

Abstract
Recently, a number of promising approaches have been developed using synthetic chemistry, materials science, and bioengineering-based strategies to address challenges in the design of more effective cancer vaccines. At the stage of initial priming, potency can be improved by maximizing vaccine delivery to lymph nodes. Because lymphatic uptake from peripheral tissues is strongly size dependent, antigens and adjuvants packaged into optimally sized nanoparticles access the lymph node with much greater efficiency than unformulated vaccines. Once primed, T cells must home to the tumor site. Because T cells acquire the necessary surface receptors in the local lymph node draining the tissue of interest, vaccines must be engineered that reach organs, such as the lung and gut, which are common sites of tumor lesions but inaccessible by traditional vaccination routes. Particulate vaccine carriers can improve antigen exposure in these organs, resulting in greater lymphocyte priming. Immunomodulatory agents can also be injected directly into the tumor site to stimulate a systemic response capable of clearing even distal lesions; materials have been designed that entrap or slowly release immunomodulators at the tumor site, reducing systemic exposure and improving therapeutic efficacy. Finally, lessons learned from the design of biomaterial-based scaffolds in regenerative medicine have led to the development of implantable vaccines that recruit and activate antigen-presenting cells to drive antitumor immunity. Overall, these engineering strategies represent an expanding toolkit to create safe and effective cancer vaccines. Cancer Immunol Res; 3(8); 836–43. ©2015 AACR.
Protein C system defects inflicted by the malaria parasite protein PfEMP1 can be overcome by a soluble EPCR variant
Authors: Bouwens Eveline A. M. , Tamayo Ibai , Turner Louise , Wang Christian W. , Stins Monique , Theander Thor G. , Petersen Jens E. V. , Hermida José , Mosnier Laurent O. , Lavstsen Thomas 
Published: July 2015

SummaryThe Endothelial Protein C receptor (EPCR) is essential for the anticoagulant and cytoprotective functions of the Protein C (PC) system. Selected variants of the malaria parasite protein, Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) associated with severe malaria, including cerebral malaria, specifically target EPCR on vascular endothelial cells. Here, we examine the cellular response to PfEMP1 engagement to elucidate its role in malaria pathogenesis. Binding of the CIDRα1.1 domain of PfEMP1 to EPCR obstructed activated PC (APC) binding to EPCR and induced a loss of cellular EPCR functions. CIDRα1.1 severely impaired endothelial PC activation and effectively blocked APC-mediated activation of protease-activated receptor-1 (PAR1) and associated barrier protective effects of APC on endothelial cells. A soluble EPCR variant (E86A-sEPCR) bound CIDRα1.1 with high affinity and did not interfere with (A)PC binding to cellular EPCR. E86A-sEPCR used as a decoy to capture PfEMP1, permitted normal PC activation on endothelial cells, normal barrier protective effects of APC, and greatly reduced cytoadhesion of infected erythrocytes to brain endothelial cells. These data imply important contributions of PfEMP1-induced protein C pathway defects in the pathogenesis of severe malaria. Furthermore, the E86A-sEPCR decoy provides a proof-of-principle strategy for the development of novel adjunct therapies for severe malaria.
Genotype-guided versus standard vitamin K antagonist dosing algorithms in patients initiating anticoagulation
Authors: Belley-Cote Emilie , Hanif Hasib , D’Aragon Frederick , Eikelboom John , Anderson Jeffrey , Borgman Mark , Jonas Daniel , Kimmel Stephen , Manolopoulos Vangelis , Baranova Ekaterina , Maitland-van der Zee Anke , Pirmohamed Munir , Whitlock Richard 
Published: July 2015

SummaryVariability in vitamin K antagonist (VKA) dosing is partially explained by genetic polymorphisms. We performed a meta-analysis to determine whether genotype-guided VKA dosing algorithms decrease a composite of death, thromboembolic events and major bleeding (pri-mary outcome) and improve time in therapeutic range (TTR). We searched MEDLINE, EMBASE, CENTRAL, trial registries and conference proceedings for randomised trials comparing genotype-guided and standard (non genotype-guided) VKA dosing algorithms in adults initiating anticoagulation. Data were pooled using a random effects model. Of the 12 included studies (3,217 patients), six reported all components of the primary outcome of mortality, thromboembolic events and major bleeding (2,223 patients, 87 events). Our meta-analysis found no significant difference between groups for the primary outcome (relative risk 0.85, 95 % confidence interval [CI] 0.54–1.34; heterogeneity X2=4.46, p=0.35, I2=10 %). Based on 10 studies (2,767 patients), TTR was significantly higher in the genotype-guided group (mean difference (MD) 4.31 %; 95 % CI 0.35, 8.26; heterogeneity X2=43.31, p< 0.001, I2=79 %). Pre-specified exploratory analyses demonstrated that TTR was significantly higher when geno-type-guided dosing was compared with fixed VKA dosing (6 trials, 997 patients: MD 8.41 %; 95 % CI 3.50,13.31; heterogeneity X2=15.18, p=0.01, I2=67 %) but not when compared with clinical algorithm-guided dosing (4 trials, 1,770 patients: MD –0.29 %; 95 % CI –2.48,1.90; heterogeneity X2=1.53, p=0.68, I2=0 %; p for interaction=0.002). In conclusion, genotype-guided compared with standard VKA dosing algorithms were not found to decrease a composite of death, thromboembolism and major bleeding, but did result in improved TTR. An improvement in TTR was observed in comparison with fixed VKA dosing algorithms, but not with clinical algorithms.
Fibroblast Angiotensin II Type 1a Receptors Contribute to Angiotensin II–Induced Medial Hyperplasia in the Ascending Aorta
Authors: Poduri Aruna , Rateri Debra L. , Howatt Deborah A. , Balakrishnan Anju , Moorleghen Jessica J. , Cassis Lisa A. , Daugherty Alan 
Published: July 2015

Objective—
Angiotensin II (Ang II) infusion causes aortic medial thickening via stimulation of angiotensin II type 1a (AT1a) receptors. The purpose of this study was to determine the cellular loci of AT1a receptors that mediate this Ang II–induced aortic pathology.

Approach and Results—
Saline or Ang II was infused into AT1a receptor floxed mice expressing Cre under control of cell-specific promoters. Initially, AT1a receptors were depleted in aortic smooth muscle cell and endothelium by expressing Cre under control of SM22 and Tie2 promoters, respectively. Deletion of AT1a receptors in either cell type had no effect on Ang II–induced medial thickening. To determine whether this effect was related to neural stimulation, AT1a receptors were depleted using an enolase 2–driven Cre. Depletion of AT1a receptors in neural cells attenuated Ang II–induced medial thickening of the ascending, but not descending aorta. Lineage tracking studies, using ROSA26-LacZ, demonstrated that enolase 2 was also expressed in adventitial cells adjacent to the region of attenuated thickening. To determine whether adventitial fibroblasts contributed to this attenuation, AT1a receptors in fibroblasts were depleted using S100A4 driven Cre. Similar to enolase 2-Cre, Ang II–induced medial thickening was attenuated in the ascending, but not the descending aorta. Lineage tracking demonstrated an increase of S100A4-LacZ positive cells in the media of the ascending region during Ang II infusion.

Conclusions—
AT1a receptor depletion in fibroblasts attenuates Ang II–induced medial hyperplasia in the ascending aorta.
Comparison of 2-Dimensional, 3-Dimensional, and Surgical Measurements of the Tricuspid Annulus Size
Authors: Dreyfus Julien , Durand-Viel Guillaume , Raffoul Richard , Alkhoder Soleiman , Hvass Ulrik , Radu Costin , Al-Attar Nawwar , Ghodbhane Walid , Attias David , Nataf Patrick , Vahanian Alec , Messika-Zeitoun David 
Published: July 2015

Background—
Associated tricuspid annuloplasty is recommended during left-heart valve surgery when the tricuspid annulus (TA) is dilated but methodology for the measurement of TA size and thresholds for TA enlargement are not clearly defined.

Methods and Results—

Measurement of the TA diameter (TAD) was prospectively performed using 2-dimensional transthoracic echocardiography (2D-TTE) in 282 patients in 4 different views (parasternal long axis, parasternal short axis, apical 4-chamber [A4C], and subcostal). TAD was also measured using 3D-transesophageal echocardiography in 183 patients (long axis), peroperatively in 120 patients who underwent a tricuspid valve surgery and using TTE (A4C) in 66 healthy volunteers. TAD was significantly different between the 4 2D-TTE views (3.85±0.58, 3.87±0.61, 4.02±0.69, and 3.92±0.65 cm, respectively;
P
<0.0001) but differences were small and the A4C was the most feasible (76%, 65%, 92%, and 73%, respectively;
P
<0.0001) and offered the highest reproducibility. TAD measured in A4C view was smaller than when measured by 3D-transesophageal echocardiography (3.90±0.63 versus 4.33±0.62 cm;
P
<0.0001) but correlation was excellent (
r
=0.84;
P
<0.0001) with a systematic 4-mm underestimation. In contrast, 2D-TTE measurements were significantly smaller and only modestly correlated to surgical measurements (4.11±0.61 versus 4.37±0.75 cm;
P
<0.0001;
r
=0.57;
P
<0.0001) which were poorly reproducible. In healthy volunteers, we suggested 42 mm or 23 mm/m
2
as pathological values for the TAD in A4C.

Conclusions—
Measurements of the TAD using 2D-TTE in A4C were highly feasible and reproducible and despite being systematically smaller than 3D measurements, accurately reflected the degree of TA enlargement as assessed using 3D transesophageal echocardiography. We proposed the thresholds that may be used in future prospective studies to demonstrate whether a preventive strategy would improve the outcome.
Multimodality Intra-Arterial Imaging Assessment of the Vascular Trauma Induced by Balloon-Based and Nonballoon-Based Renal Denervation Systems
Authors: Karanasos Antonios , Van Mieghem Nicolas , Bergmann Martin W. , Hartman Eline , Ligthart Jurgen , van der Heide Elco , Heeger Christian-H. , Ouhlous Mohamed , Zijlstra Felix , Regar Evelyn , Daemen Joost 
Published: July 2015

Background—
Renal denervation is a new treatment considered for several possible indications. As new systems are introduced, the incidence of acute renal artery wall injury with relation to the denervation method is unknown. We investigated the acute repercussion of renal denervation on the renal arteries of patients treated with balloon-based and nonballoon-based denervation systems by quantitative angiography, intravascular ultrasound, and optical coherence tomography (OCT).

Methods and Results—

Twenty-five patients (50 renal arteries) underwent bilateral renal denervation with 5 different systems, 3 of which balloon-based (Paradise [n=5], Oneshot [n=6], and Vessix V2 [n=5)]) and 2 nonballoon-based (Symplicity [n=6] and EnligHTN [n=3]). Analysis included quantitative angiography and morphometric intravascular ultrasound measurements pre and post procedure and assessment of vascular trauma (dissection, edema, or thrombus) by OCT after denervation. A significant reduction in lumen size by quantitative angiography and intravascular ultrasound was observed in nonballoon denervation but not in balloon denervation. By postdenervation OCT, dissection was seen in 14 arteries (32.6%). The percentage of frames with dissection was higher in balloon-based denervation catheters. Thrombus and edema were detected in 35 (81.4%) and 32 (74.4%) arteries, respectively. In arteries treated with balloon-based denervation that had dissection by OCT, the balloon/artery ratio was higher (1.24 [1.17–1.32] versus 1.10 [1.04–1.18];
P
<0.01).

Conclusions—
A varying extent of vascular injury was observed after renal denervation in all systems; however, different patterns were identified in balloon-based and in nonballoon-based denervation systems. In balloon denervation, the presence of dissections by OCT was associated with a higher balloon/artery ratio.
A Bayesian Hidden Markov Model of Daily Precipitation over South and East Asia
Authors: Holsclaw Tracy , Greene Arthur M. , Robertson Andrew W. , Smyth Padhraic 
Published: July 2015

Abstract
A Bayesian hidden Markov model (HMM) for climate downscaling of multisite daily precipitation is presented. A generalized linear model (GLM) component allows exogenous variables to directly influence the distributional characteristics of precipitation at each site over time, while the Markovian transitions between discrete states represent seasonality and subseasonal weather variability. Model performance is evaluated for station networks of summer rainfall over the Punjab region in northern India and Pakistan and the upper Yangtze River basin in south-central China. The model captures seasonality and the marginal daily distributions well in both regions. Extremes are reproduced relatively well in the Punjab region, but underestimated for the Yangtze. In terms of interannual variability, the combined GLM–HMM with spatiotemporal averages of observed rainfall as a predictor is shown to exhibit skill (in terms of reduced RMSE) at the station level, particularly for the Punjab region. The skill is largest for dry-day counts, moderate for seasonal rainfall totals, and very small for the number of extreme wet days.
A review of randomised controlled trials comparing ultrasound-guided foam sclerotherapy with endothermal ablation for the treatment of great saphenous varicose veins
Authors: Davies Huw OB , Popplewell Matthew , Darvall Katy , Bate Gareth , Bradbury Andrew W 
Published: July 2015

Objective The last 10 years have seen the introduction into everyday clinical practice of a wide range of novel non-surgical treatments for varicose veins. In July 2013, the UK National Institute for Health and Care Excellence recommended the following treatment hierarchy for varicose veins: endothermal ablation, ultrasound-guided foam sclerotherapy, surgery and compression hosiery. The aim of this paper is to review the randomised controlled trials that have compared endothermal ablation and ultrasound-guided foam sclerotherapy to determine if the level 1 evidence base still supports an “endothermal ablation first” strategy for the treatment of varicose veins. Methods A PubMed and OVID literature search (until 31 January 2015) was performed and randomised controlled trials comparing endothermal ablation and ultrasound-guided foam sclerotherapy were obtained. Results Although anatomical success appeared higher with endothermal ablation than ultrasound-guided foam sclerotherapy, clinical success and patient-reported outcomes measures were similar. Morbidity and complication rates were very low and not significantly different between endothermal ablation and ultrasound-guided foam sclerotherapy. Ultrasound-guided foam sclerotherapy was consistently less expensive that endothermal ablation. Conclusions All endovenous modalities appear to be successful and have a role in modern day practice. Although further work is required to optimise ultrasound-guided foam sclerotherapy technique to maximise anatomical success and minimise retreatment, the present level 1 evidence base shows there is no significant difference in clinical important outcomes between ultrasound-guided foam sclerotherapy and endothermal ablation. As ultrasound-guided foam sclerotherapy is less expensive, it is likely to be a more cost-effective option in most patients in most healthcare settings. Strict adherence to the treatment hierarchy recommended by National Institute for Health and Care Excellence seems unjustified.
Anatomic Reconstruction With a Semitendinosus Allograft for Chronic Lateral Ankle Instability
Authors: Dierckman Brian D. , Ferkel Richard D. 
Published: July 2015

Background: The modified Broström procedure has been successful for most patients with chronic lateral ankle instability (CLAI); however, a subset of patients has had unsatisfactory outcomes. For those at risk of failure, anatomic reconstruction of the lateral ankle ligaments using a semitendinosus allograft to augment the modified Broström procedure is available. Purpose: To report the results of anatomic reconstruction of the lateral ankle with a semitendinosus allograft for the treatment of CLAI. Study Design: Case series; Level of evidence, 4. Methods: This is a retrospective review of a single surgeon’s experience from 2003 to 2011 in performing anatomic lateral ankle ligament reconstruction with a semitendinosus allograft for the treatment of CLAI. Of 38 patients (40 ankles), 31 (33 ankles; 82% of patients) returned for final follow-up and constituted the study group. Preoperatively, all patients completed the American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Score (AHS) and a visual analog scale (VAS) for pain and underwent plain and stress talar tilt radiographs. At the most recent follow-up, patients were evaluated by an independent surgeon and completed the postoperative AHS, Foot-Function Index (FFI), VAS for pain, Tegner activity score, and a satisfaction survey. Patients were evaluated with plain and stress talar tilt and anterior drawer radiographs. Results: At a mean follow-up of 38 ± 30 months (range, 24-107 months), 100% of patients were completely satisfied with the procedure. AHS values significantly improved from a mean of 60.3 ± 14.4 to 87.5 ± 9.3 ( P < .0001). VAS pain scores significantly decreased from 7.3 ± 1.3 to 1.9 ± 1.8 ( P < .0001). Twenty-two of 31 patients (71%) either returned to or were 1 level below their previous preoperative or preinjury Tegner activity level. No patients developed arthritic changes beyond grade I on plain radiographs. On stress radiographs, the mean talar tilt decreased from 14.3° ± 5.4° to 3.1° ± 2.4°. The mean postoperative anterior tibiotalar translation was 1.8 ± 1.1 mm, with no patients having greater than 5 mm of translation. Conclusion: Anatomic lateral ankle ligament reconstruction with a semitendinosus allograft for the treatment of CLAI leads to high patient satisfaction, decreased pain, a stable ankle without arthritic changes, and significantly improved function.
Male Batterer Parenting Attitudes
Authors: Ferreira Regardt J. , Lauve-Moon Katie , Cannon Clare 
Published: July 2015

Objective: The purpose of the study was to investigate the differences between intimate partner violence (IPV) and parenting attitudes by race by comparing demographic, parenting, and IPV indicators for African American and White men. Method: The study employed a nonequivalent, control group design in a secondary analysis of 111 men. Results: Analyses indicated that (1) African American men had more children; (2) chi-square tests revealed no statistically significant differences between African American and Caucasian men with respect to IPV perpetration and parenting attitudes; and (3) a logistic regression model indicated that the number of children and a higher risk category for parenting attitudes were significant predictors of race group membership. Conclusion: These findings reveal that having more children is related to a higher level of stress on intimate partner relationships, and these stressors are not evenly distributed across racial groups. Batterer intervention programs should include parenting skills to help perpetrators better cope with such stresses.
The Role of Xylitol Gum Chewing in Restoring Postoperative Bowel Activity After Cesarean Section
Authors: Lee Jian Tao , Hsieh Mei-Hui , Cheng Po-Jen , Lin Jr-Rung 
Published: July 2015

Aims: The goal of this study was to evaluate the effects of xylitol gum chewing on gastrointestinal recovery after cesarean section. Methods: Women who underwent cesarean section ( N = 120) were randomly allocated into Group A (xylitol gum), Group B (nonxylitol gum), or the control group (no chewing gum). Every 2 hr post-cesarean section and until first flatus, Groups A and B received two pellets of chewing gum and were asked to chew for 15 min. The times to first bowel sounds, first flatus, and first defecation were then compared among the three groups. Results: Group A had the shortest mean time to first bowel sounds (6.9 ± 1.7 hr), followed by Group B (8 ± 1.6 hr) and the control group (12.8 ± 2.5 hr; one-way analysis of variance, p < .001; Scheffe’s post hoc comparisons, p < .05). The gum-chewing groups demonstrated a faster return of flatus than the control group did ( p < .001), but the time to flatus did not differ significantly between the gum-chewing groups. Additionally, the differences in the time to first defecation were not significant. Conclusion: After cesarean section, chewing gum increased participants’ return of bowel activity, as measured by the appearance of bowel sounds and the passage of flatus. In this context, xylitol-containing gum may be superior to xylitol-free gum.
Data reporting constraints for the lymphatic filariasis mass drug administration activities in two districts in Ghana: A qualitative study
Authors: da-Costa Vroom Frances Baaba , Aryeetey Richmond , Boateng Richard , Anto Francis , Aikins Moses , Gyapong Margaret , Gyapong John 
Published: July 2015

Objectives: Timely and accurate health data are important for objective decision making and policy formulation. However, little evidence exists to explain why poor quality routine health data persist. This study examined the constraints to data reporting for the lymphatic filariasis mass drug administration programme in two districts in Ghana. This qualitative study focused on timeliness and accuracy of mass drug administration reports submitted by community health volunteers. Methods: The study is nested within a larger study focusing on the feasibility of mobile phone technology for the lymphatic filariasis programme. Using an exploratory study design, data were obtained through in-depth interviews (n = 7) with programme supervisors and focus group discussions (n = 4) with community health volunteers. Results were analysed using thematic content analysis. Results: Reasons for delays in reporting were attributed to poor numeracy skills among community health volunteers, difficult physical access to communities, high supervisor workload, poor adherence reporting deadlines, difficulty in reaching communities within allocated time and untimely release of programme funds. Poor accuracy of data was mainly attributed to inadequate motivation for community health volunteers and difficulty calculating summaries. Conclusion: This study has shown that there are relevant issues that need to be addressed in order to improve the quality of lymphatic filariasis treatment coverage reports. Some of the factors identified are problems within the health system; others are specific to the community health volunteers and the lymphatic filariasis programme. Steps such as training on data reporting should be intensified for community health volunteers, allowances for community health volunteers should be re-evaluated and other non-monetary incentives should be provided for community health volunteers.