bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frequent hypomorphic alleles account for a significant fraction of ABCA4 disease and distinguish it from age-related macular degeneration
Authors: Zernant Jana , Lee Winston , Collison Frederick T , Fishman Gerald A , Sergeev Yuri V , Schuerch Kaspar , Sparrow Janet R , Tsang Stephen H , Allikmets Rando 
Published: April 2017

BackgroundVariation in theABCA4gene is causal for, or associated with, a wide range of phenotypes from early onset Mendelian retinal dystrophies to late-onset complex disorders such as age-related macular degeneration (AMD). Despite substantial progress in determining the causal genetic variation, even complete sequencing of the entire open reading frame and splice sites ofABCA4identifies biallelic mutations in only 60%–70% of cases; 20%–25% remain with one mutation and no mutations are found in 10%–15% of cases with clinically confirmed ABCA4 disease. This study was designed to identify missing causal variants specifically in monoallelic cases of ABCA4 disease.MethodsDirect sequencing and analysis were performed in a large familial ABCA4 disease cohort of predominately European descent (n=643). Patient phenotypes were assessed from clinical and retinal imaging data.ResultsWe determined that a hypomorphicABCA4variant c.5603A>T (p.Asn1868Ile), previously considered benign due to high minor allele frequency (MAF) (~7%) in the general population, accounts for 10% of the disease, >50% of the missing causal alleles in monoallelic cases, ~80% of late-onset cases and distinguishes ABCA4 disease from AMD. It results in a distinct clinical phenotype characterised by late-onset of symptoms (4th decade) and foveal sparing (85%). Intragenic modifying effects involving this variant and another, c.2588G>C (p.Gly863Ala) allele, were also identified.ConclusionsThese findings substantiate the causality of frequent missense variants and their phenotypic outcomes as a significant contribution to ABCA4 disease, particularly the late-onset phenotype, and its clinical variation. They also suggest a significant revision of diagnostic screening and assessment ofABCA4variation in aetiology of retinal diseases.
Temporal cascade of inflammatory cytokines and cell-type populations in monocyte chemotactic protein-1 (MCP-1)-mediated aneurysm healing
Authors: Hoh Brian L , Fazal Hanain Z , Hourani Siham , Li Mengchen , Lin Li , Hosaka Koji 
Published: April 2017

BackgroundWe have previously shown that monocyte chemotactic protein-1 (MCP-1) promotes aneurysm healing.ObjectiveTo determine the temporal cascade and durability of aneurysm healing.MethodsMurine carotid aneurysms were treated with MCP-1-releasing or poly(lactic-co-glycolic) acid (PLGA)-only coils. Aneurysm healing was assessed by quantitative measurements of intraluminal tissue ingrowth on 5 μm sections by blinded observers.ResultsAneurysm healing occurred in stages characteristic of normal wound healing. The 1st stage (day 3) was characterized by a spike in neutrophils and T cells. The 2nd stage (week 1) was characterized by an influx of macrophages and CD45+ cells significantly greater with MCP-1 than with PLGA (p<0.05). The third stage (week 2–3) was characterized by proliferation of smooth muscle cells and fibroblasts (greater with MCP-1 than with PLGA, p<0.05). The fourth stage (3–6 months) was characterized by leveling off of smooth muscle cells and fibroblasts. M1 macrophages were greater at week 1, whereas M2 macrophages were greater at weeks 2 and 3 with MCP-1 than with PLGA. Interleukin 6 was present early and increased through week 2 (p<0.05 compared with PLGA) then decreased and leveled off through 6 months. Tumour necrosis factor α was present early and remained constant through 6 months. MCP-1 and PLGA treatment had similar rates of tissue ingrowth at early time points, but MCP-1 had a significantly greater tissue ingrowth at week 3 (p<0.05), which persisted for 6 months.ConclusionsThe sequential cascade is consistent with an inflammatory model of injury, repair, and remodeling.
Plasmonic resonances of nanoparticles from large-scale quantum mechanical simulations
Authors: Zhang Xu , Xiang Hongping , Zhang Mingliang , Lu Gang 
Published: April 2017

Plasmonic resonance of metallic nanoparticles results from coherent motion of its conduction electrons, driven by incident light. For the nanoparticles less than 10 nm in diameter, localized surface plasmonic resonances become sensitive to the quantum nature of the conduction electrons. Unfortunately, quantum mechanical simulations based on time-dependent Kohn–Sham density functional theory are computationally too expensive to tackle metal particles larger than 2 nm. Herein, we introduce the recently developed time-dependent orbital-free density functional theory (TD-OFDFT) approach which enables large-scale quantum mechanical simulations of plasmonic responses of metallic nanostructures. Using TD-OFDFT, we have performed quantum mechanical simulations to understand size-dependent plasmonic response of Na nanoparticles and plasmonic responses in Na nanoparticle dimers and trimers. An outlook of future development of the TD-OFDFT method is also presented.
Microstructure and magnetic properties of Fe–6.5 wt.% Si/MnZn(Fe2O4)2 composites with core-shell structure prepared by spark plasma sintering
Authors: Yan Liang , Yan Biao 
Published: April 2017

Fe–6.5 wt.% Si powder coated with 10 wt.% MnZn(Fe2O4)2 (MnZn ferrite) was successfully prepared by using dry-type stirring ball milling. The Fe–6.5 wt.% Si/MnZn(Fe2O4)2 soft magnetic composites were prepared by subsequent spark plasma sintering. This paper aims at analyzing the microstructure and magnetic properties of Fe–6.5 wt.% Si/MnZn(Fe2O4)2 soft magnetic composites (sintering temperature: 750[Formula: see text]C, sintering pressure: 50 MPa, holding time: 8 min, heating rate: 60 K/min). Based on X-ray diffraction and scanning electron microscopy, microstructure and powder morphology were examined and magnetic measurements on bulk samples were conducted by vibrating sample magnetometer and impedance analyzer. According to the experiments results, Fe–6.5 wt.% Si/MnZn(Fe2O4)2 composites displayed a core-shell structure, and ceramic phase was observed after sintering. The Fe–6.5 wt.% Si/MnZn(Fe2O4)2 composites achieved high resistivity ([Formula: see text] m[Formula: see text]/cm) while maintaining excellent magnetic properties ([Formula: see text] emu/g). Core losses especially at medium and high frequencies were significantly reduced.
Microstructure evolution and mechanical properties of 5083 aluminum alloy joints by ultrasonic soldering
Authors: Han Dengquan , Li Yuanxing , He Yongpan , Qiu Sifu , Chen Hui 
Published: April 2017

Aluminum alloy 5083 was joined with Sn–[Formula: see text]Zn ([Formula: see text], 5, 9, 30 and 60 wt.%) filler metal by ultrasonic soldering at 400[Formula: see text]C. The joint microstructure consisted of [Formula: see text]-Sn and [Formula: see text]-Al solid–solution phases when using pure Sn solder. Zn-rich phases were observed in the joints with Sn–Zn filler metal. The Zn-rich phases grew thicker and larger with the increase in Zn content in the filler metal. The joints soldered with Sn–30Zn filler metal reached a maximum shear strength of 70 MPa. Joint cracking occurred at the interface of pure Sn and Sn–9Zn solders as indicated by SEM observation of the fracture surfaces. The locations of the fracture surface moved from the interface to the seam when using the Sn–30Zn or Sn–60Zn filler metal. The coarse Zn-rich phases were also observed on the fracture surface using Sn–60Sn solder, which results in a shear strength reduction of the joints.
Wide angle and broadband perfect absorber with compact multilayer structures
Authors: Wang Jianguo , Yin Chaoyi , Zhu Meiping , Sun Jian , Yi Kui , Shao Jianda 
Published: April 2017

We design and numerically investigate a wide angle and broadband perfect absorber with compact multilayer structures. The proposed structure is composed of three stacks of semiconductor films and one metal layer. The absorber presents a broadband absorption between 450 nm and 700 nm with an average absorption above 99.2%. For oblique incidence, the absorber shows an average absorption about 90% for a wide range of incident angles from 0[Formula: see text] to 60[Formula: see text] with p polarization and s polarization. The electrical field intensity distributions are also studied to disclose the broadband absorption mechanism. This designed broadband absorber appears to have very promising applications in solar thermal energy harvesting, thermal emitters and detection.
Effect of acute physiological free fatty acid elevation in the context of hyperinsulinemia on fiber type-specific IMCL accumulation
Authors: Chow Lisa S. , Mashek Douglas G. , Wang Qi , Shepherd Sam O. , Goodpaster Bret H. , Dubé John J. 
Published: April 2017

It is well described that increasing free fatty acids (FFAs) to high physiological levels reduces insulin sensitivity. In sedentary humans, intramyocellular lipid (IMCL) is inversely related to insulin sensitivity. Since muscle fiber composition affects muscle metabolism, whether FFAs induce IMCL accumulation in a fiber type-specific manner remains unknown. We hypothesized that in the setting of acute FFA elevation by lipid infusion within the context of a hyperinsulinemic-euglycemic clamp, IMCL will preferentially accumulate in type 1 fibers. Normal-weight participants ( n = 57, mean ± SE: age 24 ± 0.6 yr, BMI 22.2 ± 0.3 kg/m2) who were either endurance trained or sedentary by self-report were recruited from the University of Minnesota ( n = 31, n = 15 trained) and University of Pittsburgh ( n = 26, n = 14 trained). All participants underwent a hyperinsulinemic-euglycemic clamp in the context of a 6-h infusion of either lipid or glycerol control. A vastus lateralis muscle biopsy was obtained at baseline and end-infusion (6 h). The muscle biopsies were processed and analyzed at the University of Pittsburgh for fiber type-specific IMCL accumulation by Oil-Red-O staining. Regardless of training status, acute elevation of FFAs to high physiological levels (~400–600 meq/l) increased IMCL preferentially in type 1 fibers (+35 ± 11% compared with baseline, +29 ± 11% compared with glycerol control: P < 0.05). The increase in IMCL correlated with a decline in insulin sensitivity as measured by the hyperinsulinemic-euglycemic clamp ( r = −0.32, P < 0.01) independent of training status. Regardless of training status, increase of FFAs to a physiological range within the context of hyperinsulinemia shows preferential IMCL accumulation in type 1 fibers. NEW & NOTEWORTHY This novel human study examined the effects of FFA elevation in the setting of hyperinsulinemia on accumulation of fat in specific types of muscle fibers. Within the context of the hyperinsulinemic-euglycemic clamp, we found that an increase of FFAs to a physiological range sufficient to reduce insulin sensitivity is associated with preferential IMCL accumulation in type 1 fibers.
Circulating Cell-Free DNA to Guide Prostate Cancer Treatment with PARP Inhibition
Authors: Goodall Jane , Mateo Joaquin , Yuan Wei , Mossop Helen , Porta Nuria , Miranda Susana , Perez-Lopez Raquel , Dolling David , Robinson Dan R. , Sandhu Shahneen , Fowler Gemma , Ebbs Berni , Flohr Penny , Seed George , Rodrigues Daniel Nava , Boysen Gunther , Bertan Claudia , Atkin Mark , Clarke Matthew , Crespo Mateus , Figueiredo Ines , Riisnaes Ruth , Sumanasuriya Semini , Rescigno Pasquale , Zafeiriou Zafeiris , Sharp Adam , Tunariu Nina , Bianchini Diletta , Gillman Alexa , Lord Christopher J. , Hall Emma , Chinnaiyan Arul M. , Carreira Suzanne , de Bono Johann S. 
Published: April 2017

Abstract
Biomarkers for more precise patient care are needed in metastatic prostate cancer. We have reported a phase II trial (TOPARP-A) of the PARP inhibitor olaparib in metastatic prostate cancer, demonstrating antitumor activity associating with homologous recombination DNA repair defects. We now report targeted and whole-exome sequencing of serial circulating cell-free DNA (cfDNA) samples collected during this trial. Decreases in cfDNA concentration independently associated with outcome in multivariable analyses (HR for overall survival at week 8: 0.19; 95% CI, 0.06–0.56; P = 0.003). All tumor tissue somatic DNA repair mutations were detectable in cfDNA; allele frequency of somatic mutations decreased selectively in responding patients (χ2 P &lt; 0.001). At disease progression, following response to olaparib, multiple subclonal aberrations reverting germline and somatic DNA repair mutations (BRCA2, PALB2) back in frame emerged as mechanisms of resistance. These data support the role of liquid biopsies as a predictive, prognostic, response, and resistance biomarker in metastatic prostate cancer.
Significance: We report prospectively planned, serial, cfDNA analyses from patients with metastatic prostate cancer treated on an investigator-initiated phase II trial of olaparib. These analyses provide predictive, prognostic, response, and resistance data with “second hit” mutations first detectable at disease progression, suggesting clonal evolution from treatment-selective pressure and platinum resistance. Cancer Discov; 7(9); 1006–17. ©2017 AACR.
See related commentary by Domchek, p. 937.
See related article by Kondrashova et al., p. 984.
See related article by Quigley et al., p. 999.
This article is highlighted in the In This Issue feature, p. 920
Association Between Carotid Atherosclerotic Plaque Calcification and Intraplaque Hemorrhage
Authors: Lin Ruolan , Chen Shuo , Liu Gaifen , Xue Yunjing , Zhao Xihai 
Published: April 2017

Objective—
Carotid intraplaque hemorrhage (IPH) is associated with cardiovascular events. Calcification, which frequently accompanies IPH, may play a role in IPH occurrence. In this study, we aimed to investigate the associations between calcification characteristics and IPH in carotid plaques.

Approach and results—

One hundred seventeen patients with cerebrovascular symptoms and carotid plaques detected by ultrasound were recruited and underwent multicontrast magnetic resonance imaging. Advanced carotid plaques with composition measured by magnetic resonance imaging were included in the analysis. Carotid calcifications were divided into the following categories: surface, mixed, and deep calcification. They were also classified into single and multiple calcifications according to quantity. Logistic regression models utilizing generalized estimating equations were performed to evaluate the relationship between calcification and IPH. Of 117 subjects, 85 with 142 plaques were included in the final analysis, whereas 32 were excluded because of lack of plaque compositions. Of the 142 plaques, 40 (28.2%) had IPH. Plaques with IPH showed greater prevalence of calcification than those without (87.5% versus 55.9%;
P
=0.005). After adjusting for age, low-density lipoprotein, maximum wall thickness, and maximum soft plaque thickness, multiple calcifications (odd ratio, 10.1; 95% confidence interval, 3.3–30.4), surface calcification (odd ratio, 29.4; 95% confidence interval, 4.1–210.8), and mixed calcifications (odd ratio, 27.9; 95% confidence interval, 7.3–107.1) were found to be strongly associated with the presence of IPH (all
P
<0.05).

Conclusions—
Surface calcification and multiple calcifications in carotid atherosclerotic plaques are independently associated with the presence of IPH, suggesting that both quantity and location of calcification may play important roles in the occurrence of IPH. These findings may provide novel insights for understanding mechanisms of IPH.
Extracellular Cyclophilin A, Especially Acetylated, Causes Pulmonary Hypertension by Stimulating Endothelial Apoptosis, Redox Stress, and Inflammation
Authors: Xue Chao , Sowden Mark , Berk Bradford C. 
Published: April 2017

Objective—
Oxidative stress and inflammation play key roles in the development of pulmonary arterial hypertension (PAH). Cyclophilin A (CypA) is secreted in response to oxidative stress and promotes inflammation and cardiovascular disease. Endothelial cell (EC) dysfunction is an early event in the pathogenesis of PAH. We evaluated the role of extracellular CypA in PAH and compared the effects of acetylated CypA (AcK-CypA, increased by oxidative stress) and CypA on EC dysfunction.

Approach and Results—
In transgenic mice that express high levels of CypA in EC specifically, a PAH phenotype was observed at 3 months including increased right ventricular systolic pressure, α-smooth muscle actin expression in small arterioles, and CD45-positive cells in the lungs. Mechanistic analysis using cultured mouse pulmonary microvascular EC and human pulmonary microvascular EC showed that extracellular CypA and AcK-CypA stimulated EC inflammatory signals: increased VCAM1 (vascular cell adhesion molecule 1) and ICAM1 (intercellular adhesion molecule 1), phosphorylation of p65, and degradation of IkB. Extracellular CypA and AcK-CypA increased EC apoptosis measured by TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) staining, Apo-ONE assay, and caspase 3 cleavage. Oxidative stress stimulated CypA and AcK-CypA secretion, which further promoted EC oxidative stress. AcK-CypA, compared with CypA, stimulated greater increases in apoptosis, inflammation, and oxidative stress. MM284, a specific inhibitor of extracellular CypA, attenuated EC apoptosis induced by CypA and AcK-CypA.

Conclusions—
EC-derived CypA (especially AcK-CypA) causes PAH by a presumptive mechanism involving increased EC apoptosis, inflammation, and oxidative stress. Our results suggest that inhibiting secreted extracellular CypA is a novel therapeutic approach for PAH.
Role of Biomarkers for the Prevention, Assessment, and Management of Heart Failure: A Scientific Statement From the American Heart Association
Authors: Chow Sheryl L. , Maisel Alan S. , Anand Inder , Bozkurt Biykem , de Boer Rudolf A. , Felker G. Michael , Fonarow Gregg C. , Greenberg Barry , Januzzi James L. , Kiernan Michael S. , Liu Peter P. , Wang Thomas J. , Yancy Clyde W. , Zile Michael R. 
Published: April 2017

Background and Purpose:
Natriuretic peptides have led the way as a diagnostic and prognostic tool for the diagnosis and management of heart failure (HF). More recent evidence suggests that natriuretic peptides along with the next generation of biomarkers may provide added value to medical management, which could potentially lower risk of mortality and readmissions. The purpose of this scientific statement is to summarize the existing literature and to provide guidance for the utility of currently available biomarkers.

Methods:
The writing group used systematic literature reviews, published translational and clinical studies, clinical practice guidelines, and expert opinion/statements to summarize existing evidence and to identify areas of inadequacy requiring future research. The panel reviewed the most relevant adult medical literature excluding routine laboratory tests using MEDLINE, EMBASE, and Web of Science through December 2016. The document is organized and classified according to the American Heart Association to provide specific suggestions, considerations, or contemporary clinical practice recommendations.

Results:
A number of biomarkers associated with HF are well recognized, and measuring their concentrations in circulation can be a convenient and noninvasive approach to provide important information about disease severity and helps in the detection, diagnosis, prognosis, and management of HF. These include natriuretic peptides, soluble suppressor of tumorgenicity 2, highly sensitive troponin, galectin-3, midregional proadrenomedullin, cystatin-C, interleukin-6, procalcitonin, and others. There is a need to further evaluate existing and novel markers for guiding therapy and to summarize their data in a standardized format to improve communication among researchers and practitioners.

Conclusions:
HF is a complex syndrome involving diverse pathways and pathological processes that can manifest in circulation as biomarkers. A number of such biomarkers are now clinically available, and monitoring their concentrations in blood not only can provide the clinician information about the diagnosis and severity of HF but also can improve prognostication and treatment strategies.
Ischemic Stroke in Nonvalvular Atrial Fibrillation at Warfarin Initiation
Authors: Tepper Ping G. , Liu Xianchen , Hamilton Melissa , Mardekian Jack , Petkun William , Tan Wilson , Singer Daniel E. 
Published: April 2017

Background and Purpose—
Stroke risk may increase shortly after warfarin initiation in nonvalvular atrial fibrillation patients. Because of the brief period and limited number of events, large samples are needed to study this effect. We compared 30-day rates of ischemic stroke between nonvalvular atrial fibrillation patients initiating warfarin to nonwarfarin comparators using an insurance claims database.

Methods—
We identified nonvalvular atrial fibrillation patients via 1 inpatient/2 outpatient diagnosis claims from the MarketScan database, January 1, 2009, to December 31, 2010. We studied patients initiating warfarin using prescription claims and 1:1 matched 22 669 initiators to comparators based on age, sex, diagnosis date, and warfarin propensity score. Follow-up began on initiation date; patients were censored at discontinuation/switch of therapy, disenrollment, or end of the study. The median follow-up was 415 days. Cox regression was used to study differences in ischemic stroke risks between warfarin initiators and comparators while controlling for important prognostic factors.

Results—

Warfarin initiators were generally similar to comparators in clinical features but had higher CHADS
2
scores (1.26 versus 1.19). The first 30-day ischemic stroke rate was higher among warfarin initiators than comparators (1.47%/y (27/1836) versus 0.98%/y (18/1837);
P
=0.18) but lower subsequently (0.81%/y [134/16 543] versus 1.09%/y [406/37 248];
P
=0.002). Multivariable regression confirmed a significant interaction between follow-up and warfarin use with the adjusted hazard ratios (95% confidence intervals) for warfarin/comparator as 1.46 (0.80–2.65) in the first 30 days and 0.70 (0.57–0.85) afterward.

Conclusions—
Warfarin effect was qualitatively different in the first 30 days after initiation than subsequently. This is consistent with a modest increase in stroke risk occurring briefly after starting warfarin.
Significant Improvements in Pyranometer Nighttime Offsets Using High-Flow DC Ventilation
Authors: Michalsky Joseph J. , Kutchenreiter Mark , Long Charles N. 
Published: April 2017

AbstractVentilators are used to keep the domes of pyranometers clean and dry, but they affect the nighttime offset as well. This paper examines different ventilation strategies. For the several commercial single-black-detector pyranometers with ventilators examined here, high-flow-rate [50 cubic feet per minute (CFM) and higher] 12-VDC (where VDC refers to voltage direct current) fans lower the offsets, lower the scatter, and improve the predictability of the offsets during the night compared with lower-flow-rate (35 CFM) 120-VAC (where VAC refers to voltage alternating current) fans operated in the same ventilator housings. Black-and-white pyranometers sometimes show improvement with DC ventilation, but in some cases DC ventilation makes the offsets slightly worse. Since the offsets for these black-and-white pyranometers are always small, usually no more than 1 W m−2, whether AC or DC ventilated, changing their ventilation to higher CFM DC ventilation is not imperative. Future work should include all major manufacturers of pyranometers and unventilated and ventilated pyranometers. An important outcome of future research will be to clarify under what circumstances nighttime data can be used to predict daytime offsets.