bluuebunny/crossref_metadata_2025_split huggingface dataset:
The importance of endothelial dysfunction in resistance artery remodelling and cardiovascular risk
Authors: Masi Stefano , Georgiopoulos Georgios , Chiriacò Martina , Grassi Guido , Seravalle Gino , Savoia Carmine , Volpe Massimo , Taddei Stefano , Rizzoni Damiano , Virdis Agostino 
Published: April 2019

Abstract

Aims
The relationship between resistance artery remodelling and endothelial function remains unknown. In this study, we assessed (i) the capacity of endothelial function and nitric oxide (NO) availability to provide more information on the severity of resistance artery remodelling than common cardiovascular risk factors in subjects at low or high cardiovascular risk; and (ii) differences between patterns of resistance artery remodelling associated with deficit of NO availability and with exposure to cardiovascular risk factors.

Methods and results
All analyses were conducted on the microvascular data set of the Italian Society for Arterial Hypertension (SIIA) that includes 356 patients with measures of small resistance arteries remodelling acquired with pressure or wire myography. Information on endothelial function and NO availability were also available in 116 patients. The European Heart Score (HS) was used to define the total cardiovascular risk of each patient. Endothelial function was inversely related with the severity of the resistance artery remodelling, and this association remained significant after adjustment for the HS. By contrast, the HS lost its significant association with the media-to-lumen (M/L) ratio and the media cross-sectional area after adjustment for endothelial function. The strength of these associations was similar in subjects at high and low cardiovascular risk. The addition of endothelial function and NO availability to the HS significantly improved the identification of subjects at more and less severe resistance artery remodelling. A severe deficit of NO availability was associated with hypertrophic remodelling, while a higher HS was more clearly associated with eutrophic remodelling.

Conclusion
Resistance artery endothelial function and NO availability might represent important factors involved in resistance artery remodelling, independently from cardiovascular risk factor exposure.
Continuous thermodilution to assess absolute flow and microvascular resistance: validation in humans using [15O]H2O positron emission tomography
Authors: Everaars Henk , de Waard Guus A , Schumacher Stefan P , Zimmermann Frederik M , Bom Michiel J , van de Ven Peter M , Raijmakers Pieter G , Lammertsma Adriaan A , Götte Marco J , van Rossum Albert C , Kurata Akira , Marques Koen M J , Pijls Nico H J , van Royen Niels , Knaapen Paul 
Published: April 2019

Abstract

Aims
Continuous thermodilution is a novel technique to quantify absolute coronary flow and microvascular resistance (MVR). Notably, intracoronary infusion of saline elicits maximal hyperaemia, obviating the need for adenosine. The primary aim of this study was to validate continuous thermodilution in humans by comparing invasive measurements to [15O]H2O positron emission tomography (PET). As a secondary goal, absolute flow and MVR were compared between invasive measurements obtained with and without adenosine.

Methods and results
Twenty-five patients underwent coronary computed tomography angiography (CCTA), [15O]H2O PET, and invasive assessment. Absolute coronary flow and MVR were measured in the left anterior descending and left circumflex artery using a dedicated infusion catheter and a temperature/pressure sensor-tipped guidewire. Invasive measurements were performed with and without adenosine. In order to compare invasive flow measurements with PET perfusion, subtending myocardial mass of the investigated vessels was derived from CCTA using the Voronoi algorithm. Invasive and non-invasive measurements of adenosine-induced hyperaemic flow and MVR showed strong correlation (r = 0.91; P &lt; 0.001 for flow and r = 0.85; P &lt; 0.001 for MVR) and good agreement [intraclass correlation coefficient (ICC) = 0.90; P &lt; 0.001 for flow and ICC = 0.79; P &lt; 0.001 for MVR]. Absolute flow and MVR also correlated well between measurements with and without adenosine (r = 0.97; P &lt; 0.001 for flow and r = 0.98; P &lt; 0.001 for MVR) and showed good agreement (ICC = 0.96; P &lt; 0.001 for flow and ICC = 0.98; P &lt; 0.001 for MVR).

Conclusions
Continuous thermodilution is an accurate method to measure absolute coronary flow and MVR, which is evidenced by strong agreement with [15O]H2O PET derived flow and resistance. Absolute flow and MVR correlate highly between invasive measurements obtained with and without adenosine, which confirms that intracoronary infusion of room temperature saline elicits steady-state maximal hyperaemia.
Implantable cardioverter-defibrillators and survival in advanced heart failure patients with continuous-flow left ventricular assist devices: a systematic review and meta-analysis
Authors: Elkaryoni Ahmed , Badarin Firas Al , Khan Muhammad Shahzeb , Ellakany Karim , Potturi Nikitha , Poonia Jasmin , Kennedy Kevin F , Magalski Anthony , Sperry Brett W , Wimmer Alan P 
Published: April 2019

AbstractAimsImplantable cardioverter-defibrillators (ICDs) implantation in heart failure (HF) patients with reduced ejection fraction improves survival by reducing mortality secondary to arrhythmic events. Whether advanced HF patients treated with continuous-flow left ventricular assist devices (CF-LVADs) derive similar benefit is controversial.Methods and resultsWe searched PubMed, Cochrane Central Register of Controlled Trials, Embase, and Scopus from inception through November 2018 for studies examining the association between ICD implantation and all-cause mortality in patients with advanced HF and CF-LVADs. Analyses were performed using a random-effects model. Hazard ratios (HRs) were calculated with 95% confidence intervals (CIs). Heterogeneity and publication bias were formally assessed, using I2 and funnel plots, respectively. Eight observational studies with a total of 6416 patients (ICD group = 3450, no ICD group = 2966) met inclusion criteria. The majority of patients (84.6%) came from the two largest observational studies. There was no difference in mortality in the ICD and no ICD groups (HR 0.96, 95% CI 0.73–1.27, P = 0.79, I2 = 42%), and ICD implantation post-CF-LVAD was not associated with an improvement in mortality (HR 0.87, 95% CI 0.48–1.57, P = 0.64, I2 = 0%). Additionally, there was no significant difference in the likelihood of transplantation (HR 1.10, 95% CI 0.93–1.30, P = 0.28, I2 = 26%) or non-mortality adverse events between the two groups.ConclusionImplantable cardioverter-defibrillator use was not associated with improved survival in advanced HF patients with CF-LVADs. These findings underscore the need to formally study the efficacy of ICDs in this population in a dedicated randomized controlled study.
Zoster Vaccination in Older Adults: Efficacy and Public Health Implications
Authors: McElhaney Janet E , Verschoor Chris , Pawelec Graham 
Published: April 2019

Abstract
Shingles and its most common disabling complication, post-herpetic neuralgia, represent a serious public health challenge in the older population. The decline in the T-cell-mediated immune response to varicella zoster virus after age 50 is clearly associated with increased risk of viral reactivation, causing an acutely painful zoster rash, which may have a severe prodrome of dermatomal pain and persist as seriously debilitating post-herpetic neuralgia well beyond the resolution of the rash. However, new vaccines and adjuvants are being developed and trialed and are now more effective in preventing shingles and the sequelae of post-herpetic neuralgia. Those vaccines that possess the ability to enhance antigen presentation and reverse memory T-cell exhaustion, as well as diminish the immune suppressive effects of regulatory T cells, are most likely to be effective in older adults.
A general theory of age-length keys: combining the forward and inverse keys to estimate age composition from incomplete data
Authors: Ailloud Lisa E , Hoenig John M 
Published: April 2019

AbstractThere are two approaches to estimating age composition from a large number of length observations and a limited number of age determinations: the forward and the inverse age-length keys. The forward key looks at the distribution of age within each length bin while the inverse key looks at the distribution of length at each age. The former is more precise but has stringent requirements for the way data are collected. The latter approach is more widely applicable. We review the theory of the two keys with particular attention to necessary assumptions and the restrictions on when the methods are applicable. We show it is possible to combine the two approaches into a combined forward-inverse age-length key. This approach can be used to estimate age composition in several years simultaneously. It takes advantage of the efficiency of the forward key in years when that is appropriate, applies the inverse key to years with no age data, and uses a blending of the two approaches for years with moderate amounts of age data.
Systematic Evaluation of Patient-Reported Outcome Protocol Content and Reporting in Cancer Trials
Authors: Kyte Derek , Retzer Ameeta , Ahmed Khaled , Keeley Thomas , Armes Jo , Brown Julia M , Calman Lynn , Gavin Anna , Glaser Adam W , Greenfield Diana M , Lanceley Anne , Taylor Rachel M , Velikova Galina , Brundage Michael , Efficace Fabio , Mercieca-Bebber Rebecca , King Madeleine T , Turner Grace , Calvert Melanie 
Published: April 2019

Abstract

Background
Patient-reported outcomes (PROs) are captured within cancer trials to help future patients and their clinicians make more informed treatment decisions. However, variability in standards of PRO trial design and reporting threaten the validity of these endpoints for application in clinical practice.

Methods
We systematically investigated a cohort of randomized controlled cancer trials that included a primary or secondary PRO. For each trial, an evaluation of protocol and reporting quality was undertaken using standard checklists. General patterns of reporting where also explored.

Results
Protocols (101 sourced, 44.3%) included a mean (SD) of 10 (4) of 33 (range = 2–19) PRO protocol checklist items. Recommended items frequently omitted included the rationale and objectives underpinning PRO collection and approaches to minimize/address missing PRO data. Of 160 trials with published results, 61 (38.1%, 95% confidence interval = 30.6% to 45.7%) failed to include their PRO findings in any publication (mean 6.43-year follow-up); these trials included 49 568 participants. Although two-thirds of included trials published PRO findings, reporting standards were often inadequate according to international guidelines (mean [SD] inclusion of 3 [3] of 14 [range = 0–11]) CONSORT PRO Extension checklist items). More than one-half of trials publishing PRO results in a secondary publication (12 of 22, 54.5%) took 4 or more years to do so following trial closure, with eight (36.4%) taking 5–8 years and one trial publishing after 14 years.

Conclusions
PRO protocol content is frequently inadequate, and nonreporting of PRO findings is widespread, meaning patient-important information may not be available to benefit patients, clinicians, and regulators. Even where PRO data are published, there is often considerable delay and reporting quality is suboptimal. This study presents key recommendations to enhance the likelihood of successful delivery of PROs in the future.
CRISPRai for simultaneous gene activation and inhibition to promote stem cell chondrogenesis and calvarial bone regeneration
Authors: Truong Vu Anh , Hsu Mu-Nung , Kieu Nguyen Nuong Thi , Lin Mei-Wei , Shen Chih-Che , Lin Chin-Yu , Hu Yu-Chen 
Published: April 2019

Abstract
Calvarial bone healing remains difficult but may be improved by stimulating chondrogenesis of implanted stem cells. To simultaneously promote chondrogenesis and repress adipogenesis of stem cells, we built a CRISPRai system that comprised inactive Cas9 (dCas9), two fusion proteins as activation/repression complexes and two single guide RNA (sgRNA) as scaffolds for recruiting activator (sgRNAa) or inhibitor (sgRNAi). By plasmid transfection and co-expression in CHO cells, we validated that dCas9 coordinated with sgRNAa to recruit the activator for mCherry activation and also orchestrated with sgRNAi to recruit the repressor for d2EGFP inhibition, without cross interference. After changing the sgRNA sequence to target endogenous Sox9/PPAR-γ, we packaged the entire CRISPRai system into an all-in-one baculovirus for efficient delivery into rat bone marrow-derived mesenchymal stem cells (rBMSC) and verified simultaneous Sox9 activation and PPAR-γ repression. The activation/inhibition effects were further enhanced/prolonged by using the Cre/loxP-based hybrid baculovirus. The CRISPRai system delivered by the hybrid baculovirus stimulated chondrogenesis and repressed adipogenesis of rBMSC in 2D culture and promoted the formation of engineered cartilage in 3D culture. Importantly, implantation of the rBMSC engineered by the CRISPRai improved calvarial bone healing. This study paves a new avenue to translate the CRISPRai technology to regenerative medicine.
Interplay between small RNA pathways shapes chromatin landscapes in C. elegans
Authors: Gushchanskaia Ekaterina S , Esse Ruben , Ma Qicheng , Lau Nelson C , Grishok Alla 
Published: April 2019

AbstractThe nematode Caenorhabditis elegans contains several types of endogenous small interfering RNAs (endo-siRNAs) produced by RNA-dependent RNA polymerase (RdRP) complexes. Both ‘silencing’ siRNAs bound by Worm-specific Argonautes (WAGO) and ‘activating’ siRNAs bound by the CSR-1 Argonaute require the DRH-3 helicase, an RdRP component. Here, we show that, in the drh-3(ne4253) mutant deficient in RdRP-produced secondary endo-siRNAs, the silencing histone mark H3K9me3 is largely depleted, whereas in the csr-1 partially rescued null mutant strain (WM193), this mark is ectopically deposited on CSR-1 target genes. Moreover, we observe ectopic H3K9me3 at enhancer elements and an increased number of small RNAs that match enhancers in both drh-3 and csr-1 mutants. Finally, we detect accumulation of H3K27me3 at highly expressed genes in the drh-3(ne4253) mutant, which correlates with their reduced transcription. Our study shows that when abundant RdRP-produced siRNAs are depleted, there is ectopic elevation of noncoding RNAs linked to sites with increased silencing chromatin marks. Moreover, our results suggest that enhancer small RNAs may guide local H3K9 methylation.
Early Modern Voices
Authors: Varwig Bettina 
Published: April 2019

Abstract
This chapter explores early modern conceptions of voice and vocal timbre, focusing on French and German philosophical and musical writings of the long seventeenth century. It argues that a Cartesian paradigm of representation, which has tended to underpin most present-day interpretations of the music of this period, falls short of recognizing the capacity of the early modern (musical) voice to bridge the realms of the material and immaterial, of body and soul. Such a historically situated consideration of timbre – configured here as a quality arising at the intersection of the physiological and spiritual processes that constituted the human voice – thereby offers a way towards recuperating certain off-Cartesian modes of thinking, feeling and listening.
Ion Channel Permeation and Selectivity
Authors: Nogueira Juan J. , Corry Ben 
Published: April 2019

Abstract
Many biological processes essential for life rely on the transport of specific ions at specific times across cell membranes. Such exquisite control of ionic currents, which is regulated by protein ion channels, is fundamental for the proper functioning of the cells. It is not surprising, therefore, that the mechanism of ion permeation and selectivity in ion channels has been extensively investigated by means of experimental and theoretical approaches. These studies have provided great mechanistic insight but have also raised new questions that are still unresolved. This chapter first summarizes the main techniques that have provided significant knowledge about ion permeation and selectivity. It then discusses the physical mechanisms leading to ion permeation and the explanations that have been proposed for ion selectivity in voltage-gated potassium, sodium, and calcium channels.
Political Economy, Sexuality, and Intimacy
Authors: Adam Barry 
Published: April 2019

Abstract
This chapter explores how political economy shapes the social organization of sexuality and intimacy, in particular, modern formations of LGBT people. Political economy affects sexuality at three broad levels: (1) through the articulation of kinship and gender with the division of labor, it creates both openings and limits to same-sex relationships; (2) through demands imposed on contemporary workers, citizens, and consumers by neoliberalism, markets influence norms of conduct and success strategies even in personal relationships; (3) political economy generates hierarchies of entitlement and exclusion which impact LGBT peoples and the social constituencies around them who construct them as symbols of progress or decline. Reviewing both historical and anthropological evidence and the growing international divide between LGBT-affirming and repressing countries, the chapter contextualizes current contentions about the rise of homonationalism in a larger geopolitics of north and south.
Disruption of the Gene trx-m1 Impedes the Growth of Anabaena sp. PCC 7120 under Nitrogen Starvation
Authors: Deschoenmaeker Frï¿½dï¿½ric , Mihara Shoko , Niwa Tatsuya , Taguchi Hideki , Nomata Jiro , Wakabayashi Ken-Ichi , Hisabori Toru 
Published: April 2019

AbstractCyanobacteria possess a sophisticated photosynthesis-based metabolism with admirable plasticity. This plasticity is possible via the deep regulation network, the thiol-redox regulations operated by thioredoxin (hereafter, Trx). In this context, we characterized the Trx-m1-deficient mutant strain of Anabaena sp., PCC 7120 (shortly named A.7120), cultivated under nitrogen limitation. Trx-m1 appears to coordinate the nitrogen response and its absence induces large changes in the proteome. Our data clearly indicate that Trx-m1 is crucial for the diazotrophic growth of A.7120. The lack of Trx-m1 resulted in a large differentiation of heterocysts (>20% of total cells), which were barely functional probably due to a weak expression of nitrogenase. In addition, heterocysts of the mutant strain did not display the usual cellular structure of nitrogen-fixative cells. This unveiled why the mutant strain was not able to grow under nitrogen starvation.
PRELIMINARY TECHNICAL DISCUSSION ON A NEW RADON AND ITS PROGENY CONTINUOUS MONITOR USING TWO-FILTER METHOD
Authors: Igarashi Yu , Nozaki Takahiro , Mizuno Hiroyuki , Kuroki Tomohiro , Uchida Yuki , Janik Miroslaw , Iimoto Takeshi 
Published: April 2019

Abstract
Focusing on the scalability of Two-Filter Method, we started to develop a monitor for the concentration of radon and its progeny. In this study, we investigated the influence of a high-humidity environment on measuring radon concentration, and the influence of the decay chamber of the monitor on the measurement. In the high-humidity test, the conversion factor of (Bqm−3)/(cpm) tends to raise with increasing humidity. On the measurement of radon progeny, existence of the decay chamber of the monitor makes measurement sensitivity lower under environments of little aerosols. Radon concentration measurement by the developed monitor could be influenced by environmental humidity, and that counting loss could occur due to deposition of radon progeny inside of the decay chamber. Correction relating these would be needed based on the data of calibration tests.
Mycorrhizas enhance drought tolerance of citrus by altering root fatty acid compositions and their saturation levels
Authors: Wu Qiang-Sheng , He Jia-Dong , Srivastava A K , Zou Ying-Ning , Kuča Kamil 
Published: April 2019

AbstractArbuscular mycorrhizas (AMs) have the ability to enhance drought tolerance of citrus, but the underlying mechanisms have not been clearly elucidated. Considering the strong association of cell membrane fatty acid (FA) unsaturation with plant drought tolerance, the present study hypothesized that AM fungi (AMF) modulated the composition and unsaturation of FAs to enhance drought tolerance of host plants. Drought-sensitive citrus rootstocks, trifoliate orange (Poncirus trifoliata) seedlings, were inoculated with AMF (Funneliformis mosseae) for 3 months and were subsequently exposed to drought stress (DS) for 8 weeks. Mycorrhizal seedlings exhibited better plant growth performance, higher leaf water potential and lower root abscisic acid concentrations under both well-watered (WW) and DS conditions. Arbuscular mycorrhiza fungus inoculation considerably increased root methyl oleate (C18:1), methyl linoleate (C18:2) and methyl linolenate (C18:3N3) concentrations under both WW and DS conditions, and root methyl palmitoleate (C16:1) concentrations under WW, while it decreased root methyl stearate (C18:0) levels under both WW and DS. These changes in the composition of FAs of mycorrhized roots resulted in higher unsaturation index of root FAs, which later aided in reducing the oxidative damage on account of lower concentration of malondialdehyde and superoxide radicals. The changes of these FAs were a result of AMF-up-regulating root FA desaturase 2 (PtFAD2), FA desaturase 6 (PtFAD6) and Δ9 FA desaturase (PtΔ9) genes under WW and PtFAD2, PtFAD6 and Δ15 FA desaturase (PtΔ15) genes under DS conditions. Our results confirmed that mycorrhization brought significant changes in root FA compositions, in addition to regulation of gene expression responsible for increasing the unsaturation level of FAs, a predisposing physiological event for better drought tolerance of citrus.