bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scar burden is an independent and incremental predictor of cardiac resynchronisation therapy response
Authors: Harb Serge C , Toro Saleem , Bullen Jennifer A , Obuchowski Nancy A , Xu Bo , Trulock Kevin M , Varma Niraj , Rickard John , Grimm Richard , Griffin Brian , Flamm Scott D , Kwon Deborah H 
Published: July 2019

ObjectiveDetermine the prognostic impact of scar quantification (scar %) by cardiac magnetic resonance (CMR) in predicting heart failure admission, death and left ventricular (LV) function improvement following cardiac resynchronisation therapy (CRT), after controlling for the presence of left bundle branch block (LBBB), QRS duration (QRSd) and LV lead tip location and polarity.MethodsConsecutive patients who underwent CMR between 2002 and 2014 followed by CRT were included. The primary endpoint was death or heart failure admission. The secondary endpoint was change in ejection fraction (EF) ≥3 months after CRT. Cox proportional hazards, linear regression models and change in the area under the receiver operating characteristic curve (AUC) were used.ResultsA total of 84 patients were included (63% male, 51% with ischaemic cardiomyopathy). After adjusting for clinical factors, presence of LBBB and QRSd and LV lead tip location and polarity, greater scar % remained associated with a higher risk for clinical events (HR=1.06; 95% CI 1.02 to 1.10; p<0.001) and a smaller improvement in EF (slope: −0.61%; 95% CI −0.93% to 0.29%; p<0.001). When adding scar % to QRSd and LBBB, there was significant improvement in predicting clinical events at 3 years (AUC increased to 0.831 from 0.638; p=0.027) and EF increase ≥10% (AUC 0.869 from 0.662; p=0.007).ConclusionScar quantification by CMR has an incremental value in predicting response to CRT, in terms of heart failure admission, death and EF improvement, independent of the presence of LBBB, QRSd, LV lead tip location and polarity.
Urbanisation and asthma in low-income and middle-income countries: a systematic review of the urban–rural differences in asthma prevalence
Authors: Rodriguez Alejandro , Brickley Elizabeth , Rodrigues Laura , Normansell Rebecca Alice , Barreto Mauricio , Cooper Philip J 
Published: July 2019

BackgroundUrbanisation has been associated with temporal and geographical differences in asthma prevalence in low-income and middle-income countries (LMICs). However, little is known of the mechanisms by which urbanisation and asthma are associated, perhaps explained by the methodological approaches used to assess the urbanisation-asthma relationship.ObjectiveThis review evaluated how epidemiological studies have assessed the relationship between asthma and urbanisation in LMICs, and explored urban/rural differences in asthma prevalence.MethodsAsthma studies comparing urban/rural areas, comparing cities and examining intraurban variation were assessed for eligibility. Included publications were evaluated for methodological quality and pooled OR were calculated to indicate the risk of asthma in urban over rural areas.ResultsSeventy articles were included in our analysis. Sixty-three compared asthma prevalence between urban and rural areas, five compared asthma prevalence between cities and two examined intraurban variation in asthma prevalence. Urban residence was associated with a higher prevalence of asthma, regardless of asthma definition: current-wheeze OR:1.46 (95% CI:1.22 to 1.74), doctor diagnosis OR:1.89 (95% CI:1.47 to 2.41), wheeze-ever OR:1.44 (95% CI:1.15 to 1.81), self-reported asthma OR:1.77 (95% CI:1.33 to 2.35), asthma questionnaire OR:1.52 (95% CI:1.06 to 2.16) and exercise challenge OR:1.96 (95% CI:1.32 to 2.91).ConclusionsMost evidence for the relationship between urbanisation and asthma in LMICs comes from studies comparing urban and rural areas. These studies tend to show a greater prevalence of asthma in urban compared to rural populations. However, these studies have been unable to identify which specific characteristics of the urbanisation process may be responsible. An approach to understand how different dimensions of urbanisation, using contextual household and individual indicators, is needed for a better understanding of how urbanisation affects asthma.PROSPERO registration numberCRD42017064470.
Antimicrobial peptides, disease severity and exacerbations in bronchiectasis
Authors: Sibila Oriol , Perea Lídia , Cantó Elisabet , Shoemark Amelia , Cassidy Diane , Smith Alexandria Holly , Suarez-Cuartin Guillermo , Rodrigo-Troyano Ana , Keir Holly R , Oriano Martina , Ong Samantha , Vidal Silvia , Blasi Francesco , Aliberti Stefano , Chalmers James D 
Published: July 2019

RationaleRecently a frequent exacerbator phenotype has been described in bronchiectasis, but the underlying biological mechanisms are unknown. Antimicrobial peptides (AMPs) are important in host defence against microbes but can be proinflammatory in chronic lung disease.ObjectivesTo determine pulmonary and systemic levels of AMP and their relationship with disease severity and future risk of exacerbations in bronchiectasis.MethodsA total of 135 adults with bronchiectasis were prospectively enrolled at three European centres. Levels of cathelicidin LL-37, lactoferrin, lysozyme and secretory leucocyte protease inhibitor (SLPI) in serum and sputum were determined at baseline by ELISA. Patients were followed up for 12 months. We examined the ability of sputum AMP to predict future exacerbation risk.Measurements and main resultsAMP levels were higher in sputum than in serum, suggesting local AMP release. Patients with more severe disease at baseline had dysregulation of airway AMP. Higher LL-37 and lower SLPI levels were associated with Bronchiectasis Severity Index, lower FEV1(forced expiratory volume in 1 s) andPseudomonas aeruginosainfection. Low SLPI levels were also associated with the exacerbation frequency at baseline. During follow-up, higher LL-37 and lower SLPI levels were associated with a shorter time to the next exacerbation, whereas LL-37 alone predicted exacerbation frequency over the next 12 months.ConclusionsPatients with bronchiectasis showed dysregulated sputum AMP levels, characterised by elevated LL-37 and reduced SLPI levels in the frequent exacerbator phenotype. Elevated LL-37 and reduced SLPI levels are associated withPseudomonas aeruginosainfection and can predict future risk of exacerbations in bronchiectasis.
Vitamin D for secondary prevention of acute wheeze attacks in preschool and school-age children
Authors: Stefanidis Christos , Martineau Adrian R , Nwokoro Chinedu , Griffiths Christopher J , Bush Andrew 
Published: July 2019

IntroductionVitamin D is best known for its role in bone health; however, the discovery of the vitamin D receptor and the expression of the gene encoding the vitamin D 1α-hydroxylase (CYP27B1) enzyme in a wide variety of tissues including immune cells and respiratory epithelium has led to the discovery of potential roles for vitamin D in the prevention of acute wheeze.MethodsWe review here the literature concerning the relationships between circulating 25-hydroxyvitamin D (25(OH)D) concentration and secondary prevention of acute wheeze attacks in preschool and school-age children.ResultsEpidemiological data suggest that vitamin D insufficiency (25(OH)D <75 nmol/L) is highly prevalent in preschool and school-age children with wheeze. Preschool age children with a history of wheeze attacks and circulating 25(OH)D <75 nmol/L are at increased risk and frequency of future acute wheeze. However, no consistent association between low vitamin D status and risk of acute wheeze is reported in school-age children. Seven randomised controlled trials (RCTs) with relatively small sample sizes (30–430) and variable quality showed inconsistent results regarding the effect of oral vitamin D supplementation during childhood on the risk of asthma attacks, asthma symptom control, inhaled corticosteroid requirements, spirometry and unscheduled healthcare attendances for wheeze. A RCT showed that vitamin D supplementation had no effect on the frequency of unplanned healthcare attendances due to acute wheeze in 22 preschool children.DiscussionAn evidence-based recommendation for the use of vitamin D as a preventive therapy for wheeze attacks cannot be made until results of further trials are available. The assessment of circulating 25(OH)D concentration and the optimisation of vitamin D status to prevent acute respiratory tract infections, and to maintain skeletal and general health in preschool and school-age children with acute wheeze is worthwhile in its own right, but whether this will reduce the risk of acute wheeze attacks is unclear.
Ventilation following established ARDS: a preclinical model framework to improve predictive power
Authors: Oakley Charlotte , Koh Marissa , Baldi Rhianna , Soni Sanooj , O'Dea Kieran , Takata Masao , Wilson Michael 
Published: July 2019

BackgroundDespite advances in understanding the pathophysiology of acute respiratory distress syndrome, effective pharmacological interventions have proven elusive. We believe this is a consequence of existing preclinical models being designed primarily to explore biological pathways, rather than predict treatment effects. Here, we describe a mouse model in which both therapeutic intervention and ventilation were superimposed onto existing injury and explored the impact of β-agonist treatment, which is effective in simple models but not clinically.MethodsMice had lung injury induced by intranasal lipopolysaccharide (LPS), which peaked at 48 hours post-LPS based on clinically relevant parameters including hypoxaemia and impaired mechanics. At this peak of injury, mice were treated intratracheally with either terbutaline or tumour necrosis factor (TNF) receptor 1-targeting domain antibody, and ventilated with moderate tidal volume (20 mL/kg) to induce secondary ventilator-induced lung injury (VILI).ResultsVentilation of LPS-injured mice at 20 mL/kg exacerbated injury compared with low tidal volume (8 mL/kg). While terbutaline attenuated VILI within non-LPS-treated animals, it was ineffective to reduce VILI in pre-injured mice, mimicking its lack of clinical efficacy. In contrast, anti-TNF receptor 1 antibody attenuated secondary VILI within pre-injured lungs, indicating that the model was treatable.ConclusionsWe propose adoption of a practical framework like that described here to reduce the number of ultimately ineffective drugs reaching clinical trials. Novel targets should be evaluated alongside interventions which have been previously tested clinically, using models that recapitulate the (lack of) clinical efficacy. Within such a framework, outperforming a failed pharmacologic should be a prerequisite for drugs entering trials.
Primary defects in lipid handling and resistance to exercise in myotubes from obese donors with and without type 2 diabetes
Authors: Løvsletten Nils Gunnar , Rustan Arild C. , Laurens Claire , Thoresen G. Hege , Moro Cedric , Nikolić Nataša 
Published: July 2019

Several studies have shown that human primary myotubes retain the metabolic characteristic of their donors in vitro. We have demonstrated, along with other researchers, a reduced lipid turnover and fat oxidation rate in myotubes derived from obese donors with and without type 2 diabetes (T2D). Because exercise is known to increase fat oxidative capacity in skeletal muscle, we investigated if in vitro exercise could restore primary defects in lipid handling in myotubes of obese individuals with and without T2D compared with lean nondiabetic donors. Primary myotubes cultures were derived from biopsies of lean, obese, and T2D subjects. One single bout of long-duration exercise was mimicked in vitro by electrical pulse stimulation (EPS) for 24 h. Lipid handling was measured using radiolabeled palmitate, metabolic gene expression by real-time qPCR, and proteins by Western blot. We first showed that myotubes from obese and T2D donors had increased uptake and incomplete oxidation of palmitate. This was associated with reduced mitochondrial respiratory chain complex II, III, and IV protein expression in myotubes from obese and T2D subjects. EPS stimulated palmitate oxidation in lean donors, while myotubes from obese and T2D donors were refractory to this effect. Interestingly, EPS increased total palmitate uptake in myotubes from lean donors while myotubes from T2D donors had a reduced rate of palmitate uptake into complex lipids and triacylglycerols. Novelty Myotubes from obese and T2D donors are characterized by primary defects in palmitic acid handling. Both obese and T2D myotubes are partially refractory to the beneficial effect of exercise on lipid handling.
Optimization and Extension of Stream-Relation Joins
Authors: Naeem M. Asif 
Published: July 2019

Online stream processing is an emerging research area in the field of computer science. Semi-stream processing is a particular type of stream processing where a stream of data is processed with a disk-based relation. A semi-stream join operator is required to implement this operation. Many semi-stream joins use a queue of stream tuples to amortize access cost for the disk-based relation, and use an index to allow directed access to the relation, avoiding the loading of unnecessary partition of [Formula: see text]. In such a situation, the question arises which [Formula: see text] partitions should be accessed, as any stream tuple from the queue could serve as a lookup element for accessing the relation index. Existing algorithms use simple safe and correct strategies, but are not optimal in the sense that they maximize the join service rate. This paper makes two contributions: first contribution is in terms of optimization in which we analyze strategies for selecting an appropriate lookup element, particularly for skewed stream data. We show that a good selection strategy can improve service rate of the existing join algorithms significantly. Second contribution is in terms of extension in which we develop multi-stage join for semi-stream join algorithms. Multi-stage join is important when stream data needs to be joined with two or more tables in the relation e.g., stream of sales data needs information to be added from product and customer tables in the relation. To the best of our knowledge, none of the existing algorithms implement this feature. For the service rate evaluation we use two well-performed existing algorithms CACHEJOIN and HYBRIDJOIN. We evaluate the service rate using real, TPC-H, and synthetic datasets with a known skewed distribution. We also present the cost model for our multi-stage join.
Cardioprotection by the mitochondrial unfolded protein response requires ATF5
Authors: Wang Yves T. , Lim Yunki , McCall Matthew N. , Huang Kai-Ting , Haynes Cole M. , Nehrke Keith , Brookes Paul S. 
Published: July 2019

The mitochondrial unfolded protein response (UPRmt) is a cytoprotective signaling pathway triggered by mitochondrial dysfunction. UPRmt activation upregulates chaperones, proteases, antioxidants, and glycolysis at the gene level to restore proteostasis and cell energetics. Activating transcription factor 5 (ATF5) is a proposed mediator of the mammalian UPRmt. Herein, we hypothesized pharmacological UPRmt activation may protect against cardiac ischemia-reperfusion (I/R) injury in an ATF5-dependent manner. Accordingly, in vivo administration of the UPRmt inducers oligomycin or doxycycline 6 h before ex vivo I/R injury (perfused heart) was cardioprotective in wild-type but not global Atf5−/− mice. Acute ex vivo UPRmt activation was not cardioprotective, and loss of ATF5 did not impact baseline I/R injury without UPRmt induction. In vivo UPRmt induction significantly upregulated many known UPRmt-linked genes (cardiac quantitative PCR and Western blot analysis), and RNA-Seq revealed an UPRmt-induced ATF5-dependent gene set, which may contribute to cardioprotection. This is the first in vivo proof of a role for ATF5 in the mammalian UPRmt and the first demonstration that UPRmt is a cardioprotective drug target. NEW & NOTEWORTHY Cardioprotection can be induced by drugs that activate the mitochondrial unfolded protein response (UPRmt). UPRmt protection is dependent on activating transcription factor 5 (ATF5). This is the first in vivo evidence for a role of ATF5 in the mammalian UPRmt.
Comparison of Inverse Laplace and Numerical Inversion Methods for Obtaining Z-Depth Profiles of Diffraction Data
Authors: Zhu Xiaojing , Predecki Paul , Ballard Benjamin 
Published: July 2019

Abstract
Two different inversion methods, the inverse Laplace method and the linear constrained numerical method, for retrieving the z-profiles of diffraction data from experimentally obtained τ-profiles were compared using tests with a known function as the original z-profile. Two different real data situations were simulated to determine the effects of specimen thickness and missing τ-profiles data at small τ-values on the retrieved z-profiles. The results indicate that although both methods are able to retrieve the z-profiles in the bulk specimens satisfactorily, the numerical method can be used for thin film samples as well. Missing τ-profile data at small τ values causes error in the retrieved z-profiles with both methods, particularly when the trend of the τ-profile at small τ is significantly changed because of the missing data
Investigation of Residual Stresses in a Sleeve Coldworked Lug Specimen by Neutron and X-ray Diffraction
Authors: Lin R. , Jaensson B. , Holden T. M. , Rogge R. B. , Root J. H. 
Published: July 2019

Sleeve coldworking (SCW) is a mechanical process used in the aircraft industry to strengthen fastener holes of structural parts. By cold-expanding the holes, compressive residual stresses and a high dislocation density are introduced around the holes, the effect of which is to counteract the initiation and propagation of fatigue cracks and thus increase the fatigue life of the parts. The knowledge of residual stress due to SCW is therefore crucial for assessing the fatigue properties of a treated part. In this study, residual stresses were investigated, by employing neutron and X-ray diffraction methods, in a lug specimen that was sleeve coldworked and fatigued.
The specimen had been used for testing the influence of the SCW process on fatigue life and crack propagation behaviour under constant amplitude or variable amplitude cyclic loading.
Development of a Mercuric Iodide Detector Array For In-Vivo X-Ray Imaging
Authors: Patt Bradley E. , Iwanczyk Jan S. , Tornai Martin P. , Levin Craig S. , Hoffman Edward J. 
Published: July 2019

Abstract
A nineteen element mercuric iodide (HgI2) detector array has been developed in order to investigate the potential of using this technology for in-vivo x-ray and gamma-ray imaging. A prototype cross-grid detector array was constructed with hexagonal pixels of 1.9 mm diameter (active area = 3.28 mm2) and 0.2 mm thick septa. The overall detector active area is roughly 65 mm2. A detector thickness of 1.2 mm was used to achieve about 100% efficiency at 60 keV and 67% efficiency at 140 keV The detector fabrication, geometry and structure were optimized for charge collection and to minimize crosstalk between elements. A section of a standard high resolution cast-lead gamma-camera collimator was incorporated into the detector to provide collimation matching the discrete pixel geometry. Measurements of spectral and spatial performance of the array were made using 241-Am and 99m-Tc sources. These measurements were compared with similar measurements made using an optimized single HgI2 x-ray detector with active area of about 3 mm2 and thickness of 500 μm.
X-Ray Diffraction Study of BaNd2CuO5 at High Pressures
Authors: Wong-Ng Winnie , Piermarini Gasper J. , Gallas Marcia R. 
Published: July 2019

Abstract
The volume compression of BaNd2CuO5 has been measured to 8.7 GPa utilizing a diamond anvil high pressure eel and energy dispersive x-ray powder diffraction. The pressure dependence of the volume of the tetragonal unit cell is linear and follows the equation V = -1.6I5P + 260.622 determined by a least-squares fit of the data. Compression of the unit cell parameters of BaNd2CuO5 exhibit isotropic behavior within our experimental error. From the observed data, the bulk modulus of BaNd2CuO5 is determined to be 161 ± 6 GPa and the Young's modulus is estimated to be 193 ± 6 GPa. No evidence of a pressure-induced phase transformation in BaNd2CuO5 was found in the pressure range studied.
Phase I Trial of an ICAM-1-Targeted Immunotherapeutic-Coxsackievirus A21 (CVA21) as an Oncolytic Agent Against Non Muscle-Invasive Bladder Cancer
Authors: Annels Nicola E. , Mansfield David , Arif Mehreen , Ballesteros-Merino Carmen , Simpson Guy R. , Denyer Mick , Sandhu Sarbjinder S. , Melcher Alan A. , Harrington Kevin J. , Davies Bronwyn , Au Gough , Grose Mark , Bagwan Izhar , Fox Bernard , Vile Richard , Mostafid Hugh , Shafren Darren , Pandha Hardev S. 
Published: July 2019

AbstractPurpose:The CANON [CAVATAK in NON–muscle-invasive bladder cancer (NMIBC)] study evaluated a novel ICAM-1–targeted immunotherapeutic-coxsackievirus A21 as a novel oncolytic agent against bladder cancer.Patients and Methods:Fifteen patients enrolled in this “window of opportunity” phase I study, exposing primary bladder cancers to CAVATAK prior to surgery. The first 9 patients received intravesical administration of monotherapy CAVATAK; in the second stage, 6 patients received CAVATAK with a subtherapeutic dose of mitomycin C, known to enhance expression of ICAM-1 on bladder cancer cells. The primary endpoint was to determine patient safety and maximum tolerated dose (MTD). Secondary endpoints were evidence of viral replication, induction of inflammatory cytokines, antitumor activity, and viral-induced changes in resected tissue.Results:Clinical activity of CAVATAK was demonstrated by induction of tumor inflammation and hemorrhage following either single or multiple administrations of CAVATAK in multiple patients, and a complete resolution of tumor in 1 patient. Whether used alone or in combination with mitomycin C, CAVATAK caused marked inflammatory changes within NMIBC tissue biopsies by upregulating IFN-inducible genes, including both immune checkpoint inhibitory genes (PD-L1 and LAG3) and Th1-associated chemokines, as well as the induction of the innate activator RIG-I, compared with bladder cancer tissue from untreated patients. No significant toxicities were reported in any patient, from either virus or combination therapy.Conclusions:The acceptable safety profile of CAVATAK, proof of viral targeting, replication, and tumor cell death together with the virus-mediated increases in “immunological heat” within the tumor microenvironment all indicate that CAVATAK may be potentially considered as a novel therapeutic for NMIBC.