bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of source plasma from self‐identified vaccinated or convalescent donors during the 2009 H1N1 pandemic
Authors: Khalenkov Alexey , He Yong , Reed Jennifer L. , Kreil Thomas R. , McVey John , Norton Malgorzata , Scott John , Scott Dorothy E. 
Published: February 2018

BACKGROUNDInfluenza immune globulin, manufactured from plasma of convalescent or vaccinated donors has been proposed as a potential therapy for severe influenza. In 2009, a program was initiated to collect plasma from donors who self‐identified as having had H1N1 influenza or having received the H1N1 pandemic vaccine. The goal of this study was to determine the efficiency of donor screening by self‐identification without antibody testing, and to evaluate demographic predictors of high‐titer donations.STUDY DESIGN AND METHODSPlasma samples from self‐identified or control donors were randomly selected to evaluate hemagglutination inhibition (HAI) antibody responses. HAI titers were correlated with donor age, gender, location, and influenza exposure history.RESULTSBoth self‐identified vaccinated and convalescent donor groups had higher geometric mean titers (GMTs) against A/California/07/2009 (H1N1) virus compared to the control donors (39.9, 24, and 8.5, respectively). The proportion of samples with titers ≥64 in vaccinated, convalescent, and control donors were 54%, 37%, and 10%, respectively. Donations with titers ≤16 were predominant in control donors (80%) and substantial in convalescent (47%) and vaccinated (40%) donors. Titers did not correlate with donor age, gender, or geographical location. GMTs for vaccinated donors were significantly higher than for convalescent donors and in both groups significantly higher than in the control.CONCLUSIONTargeted collection of plasma containing high levels of anti‐influenza antibodies from self‐identified donors was effective, but could be further improved by reducing the number of low‐titer donations. More selective donor screening and/or testing for influenza antibodies could increase the potency of an influenza antibody‐rich immune globulin (FLUIGIV).
Comparison of detergent‐based decellularization protocols for the removal of antigenic cellular components in porcine aortic valve
Authors: Liu Xiaohong , Li Ning , Gong Dejun , Xia Cuiping , Xu Zhiyun 
Published: February 2018

AbstractBackgroundVarious detergent‐based protocols are used to remove cells and cellular debris in porcine aortic valve (PAV). However, the removal of antigenic cellular components has not been thoroughly elucidated to date. In this study, we used 4 detergent‐based protocols to decellularize PAVs and aimed to evaluate their effects on removing antigenic cellular components.MethodsPorcine aortic valves were decellularized using sodium dodecyl sulfate (SDS), SDS in combination with sodium deoxycholate (SDS/SD), Triton X‐100, and Triton X‐100 in combination with SD (Triton X‐100/SD), respectively. Untreated PAVs were used as controls. Immunohistochemical and SDS‐polyacrylamide gel electrophoresis (SDS‐PAGE) analyses were performed to determine the removal of antigenic protein components. Histological, biochemical, and biomechanical analyses were performed to determine the preservation and mechanical properties of the extracellular matrix. PAV tissues were implanted subcutaneously in Sprague Dawley rats to evaluate the host immune response. Implanted PAVs were taken out at the indicated time points for histological and immunohistochemical examinations.ResultsAll 4 protocols effectively removed the membrane antigenic proteins major histocompatibility complex I molecule and galactose‐α‐1,3 galactose. The SDS/SD protocol was the most effective method to remove the cytoplasmic cytoskeletal proteins, vimentin and α‐SMA, and SDS alone partly removed vimentin protein. The SDS/SD protocol was the most effective method to remove nuclear DNA with residual DNA below 50 ng/mg, followed by the SDS protocol with residual DNA of 74.9 ng/mg. The SDS protocol was the most effective method to remove proteins ranged from 10 to 55 kDa, followed by the SDS/SD protocol. SDS and SDS/SD PAV implants attracted fewer neutrophils in vivo on postoperative day 3. The infiltration of macrophages and T lymphocytes was significantly lower in SDS and SDS/SD implants on days 14 and day 28. All of the decellularized protocols that were examined greatly reduced the contents of collagen, elastin, and glycosaminoglycan compared to controls. Biomechanical analysis revealed significant differences in ultimate tensile strength and Young's modulus between control PAVs and decellularized PAVs generated using SDS, SDS/SD, Triton X‐100, or Triton X‐100/SD.ConclusionsThese results indicated that SDS‐based protocols more effectively removed antigenic cellular components compared to Triton X‐100‐based protocols. These results are clinically significant because complete removal of antigenic determinants is critical to decrease adverse immune‐mediated and inflammatory responses to a PAV when used in xenogeneic application.
GRL-079, a Novel HIV-1 Protease Inhibitor, Is Extremely Potent against Multidrug-Resistant HIV-1 Variants and Has a High Genetic Barrier against the Emergence of Resistant Variants
Authors: Delino Nicole S. , Aoki Manabu , Hayashi Hironori , Hattori Shin-ichiro , Chang Simon B. , Takamatsu Yuki , Martyr Cuthbert D. , Das Debananda , Ghosh Arun K. , Mitsuya Hiroaki 
Published: February 2018

ABSTRACT

We identified four novel nonpeptidic human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs), GRL-078, -079, -077, and -058, containing an alkylamine at the C-5 position of P2 tetrahydropyrano-tetrahydrofuran (Tp-THF) and a P2′ cyclopropyl (Cp) (or isopropyl)-aminobenzothiazole (Abt) moiety. Their 50% effective concentrations (EC
50
s) were 2.5 to 30 nM against wild-type HIV-1
NL4-3
, 0.3 to 6.7 nM against HIV-2
EHO
, and 0.9 to 90 nM against laboratory-selected PI-resistant HIV-1 and clinical HIV-1 variants resistant to multiple FDA-approved PIs (HIV
MDR
). GRL-078, -079, -077, and -058 also effectively blocked the replication of HIV-1 variants highly resistant to darunavir (DRV) (HIV
DRV
r
p51
), with EC
50
s of 38, 62, 61, and 90 nM, respectively, while four FDA-approved PIs examined (amprenavir, atazanavir, lopinavir [LPV], and DRV) had virtually no activity (EC
50
s of >1,000 nM) against HIV
DRV
r
p51
. Structurally, GRL-078, -079, and -058 form strong hydrogen bond interactions between Tp-THF modified at C-5 and Asp29/Asp30/Gly48 of wild-type protease, while the P2′ Cp-Abt group forms strong hydrogen bonds with Asp30′. The Tp-THF and Cp-Abt moieties also have good nonpolar interactions with protease residues located in the flap region. For selection with LPV and DRV by use of a mixture of 11 HIV
MDR
strains (HIV
11MIX
), HIV
11MIX
became highly resistant to LPV and DRV over 13 to 32 and 32 to 41 weeks, respectively. However, for selection with GRL-079 and GRL-058, HIV
11MIX
failed to replicate at >0.08 μM and >0.2 μM, respectively. Thermal stability results supported the highly favorable anti-HIV-1 potency of GRL-079 as well as other PIs. The present data strongly suggest that the P2 Tp-THF group modified at C-5 and the P2′ Abt group contribute to the potent anti-HIV-1 profiles of the four PIs against HIV-1
NL4-3
and a wide spectrum of HIV
MDR
strains.
Molecular and Functional Study of a Branching Sucrase-Like Glucansucrase Reveals an Evolutionary Intermediate between Two Subfamilies of the GH70 Enzymes
Authors: Yan Minghui , Wang Bing-hua , Xu Xiaofen , Chang Peng , Hang Feng , Wu Zhengjun , You Chunping , Liu Zhenmin 
Published: February 2018

ABSTRACT
Glucansucrases (GSs) in glycoside hydrolase family 70 (GH70) catalyze the synthesis of α-glucans from sucrose, a reaction that is widely seen in lactic acid bacteria (LAB). These enzymes have been implicated in many aspects of microbial life. Products of GSs have great commercial value as food supplements and medical materials; therefore, these enzymes have attracted much attention from both science and industry. Certain issues concerning the origin and evolution of GSs are still to be addressed, although an increasing number of GH70 enzymes have been characterized. This study describes a GS enzyme with the appearance of a branching sucrase (BrS). Structural analysis indicated that this GS enzyme produced a type of glucan composed of an α-(1→6) glucosidic backbone and α-(1→4) branches, as well as a considerable amount of α-(1→3) branches, distinguishing it from the GSs identified so far. Moreover, sequence-based analysis of the catalytic core of this enzyme suggested that it might be an evolutionary intermediate between the BrS and GS subgroups. These results provide an evolutionary link between these subgroups of GH70 enzymes and shed new light on the origination of GSs.

IMPORTANCE
GH70 GSs catalyze the synthesis of α-glucans from sucrose, a reaction that is widely seen in LAB. Products of these enzymes have great commercial value as food supplements and medical materials. Moreover, these enzymes have attracted much attention from scientists because they have potential in tailored synthesis of α-glucans with desired structures and properties. Although more and more GSs have been characterized, the origin and evolution of these enzymes have not been well addressed. This study describes a GS with the appearance of a BrS (i.e., high levels of similarity to BrSs in sequence analysis). Further analysis indicated that this enzyme synthesized a type of insoluble glucan composed of an α-(1→6) glucosidic backbone and many α-(1→4)- and α-(1→3)-linked branches, the linkage composition of which has rarely been reported in the literature. This BrS-like GS enzyme might be an evolutionary intermediate between BrS and GS enzymes.
No inferiority of Tonbridge thrombectomy device for acute thrombus retrial compared with Solitaire device: an experimental evaluation with a canine distal external carotid-maxillary artery occlusion model
Authors: Zhou Geng , Li Ming-Hua , Lu Hai-Tao , Deng Jiang-Shan , Zhao Yu-Wu , Wang Yi Xiang J , Zhu Yue-Qi 
Published: February 2018

IntroductionMechanical thrombectomy (MT) has been widely accepted as a safe and effective treatment for acute ischemic stroke (AIS). Development of stent retriever devices has been intensively developed over the past two decades. In this study, we compared the effectiveness and safety of a new thrombectomy device with Solitaire FR for the treatment of AIS models.MethodsMechanical performance of stent retrievers was tested in vitro. Thrombin-induced thrombus was pre-injected into the right distal external carotid-maxillary artery in 18 dogs to create an acute thrombus occlusion model, and these animals were divided into a Tonbridge group (n=9, with Tonbridge stent Tonbridge Medical Technology) and a Solitaire group as control (n=9, with Solitaire stent, ev3 Neurovascular). Final flow restoration, side branches, recanalization time, distal vessel embolism, and device-related complications were recorded and compared. A post-procedure angiogram was obtained at 30 and 90 days after thrombectomy. Device manipulation-related damage to the arterial walls was evaluated histologically.ResultsIn vitro test showed that the maximum friction within the microcatheter was 0.763 for the Tonbridge device and 0.784 n for the Solitaire (P>0.05). Slight increase in radial force was noticed for the Tonbridge (0.035 N/mm vs 0.031 N/mm of Solitaire, P>0.05). Eighteen and 16 retriever attempts were done in the Tonbridge (mean 2.0 attempts) and the Solitaire (mean 1.8 attempts) groups (P=0.74). The Tonbridge device led to good flow restoration in all nine (100%) models compared with eight (88.9%) in the Solitaire group (P=0.30). Side branches' influence (P=0.39), distal thromboembolism (P=0.60), and device-related complications (P=1.00) found no difference between the two groups. The rates of disruption of the internal elastic lamina (IEL) were 8.3% (2/24) and 4.2% (1/24) of the specimens, respectively (P=0.683). TICI 2b/3 flow of the right CCA were similar between the two groups at 1 (6/6 vs 6/6) and 3 months (6/6 vs 6/6) follow-up (P>0.05).ConclusionOur preliminary study indicated this new device was technically feasible and effective to be used in thrombectomy for the treatment of acute thrombus occlusion in canine models.
Lung clearance index to monitor treatment response in pulmonary exacerbations in preschool children with cystic fibrosis
Authors: Rayment Jonathan H , Stanojevic Sanja , Davis Stephanie D , Retsch-Bogart George , Ratjen Felix 
Published: February 2018

BackgroundAntibiotic treatment for pulmonary symptoms in preschool children with cystic fibrosis (CF) varies among clinicians. The lung clearance index (LCI) is sensitive to early CF lung disease, but its utility to monitor pulmonary exacerbations in young children has not been assessed.ObjectiveWe aim to (1) understand how LCI changes during lower respiratory tract symptoms relative to a recent clinically stable measurement, (2) determine whether LCI can identify antibiotic treatment response and (3) compare LCI changes to changes in spirometric indices.MethodsLCI and spirometry were measured at quarterly clinic visits over a 12-month period in preschool children with CF. Symptomatic visits were identified and classified as treated or untreated. Treatment response was estimated using propensity score matching methods.Results104 symptomatic visits were identified in 78 participants. LCI increased from baseline in both treated (mean relative change +23.8% (95% CI 16.2 to 31.4)) and untreated symptomatic visits (mean relative change +11.2% (95% CI 2.4 to 19.9)). A significant antibiotic treatment effect was observed when LCI was used as the outcome measure (average treatment effect −15.5% (95% CI −25.4 to −5.6)) but not for z-score FEV1.ConclusionLCI significantly deteriorated with pulmonary symptoms relative to baseline and improved with antibiotic treatment. These data suggest that LCI may have a role in the routine clinical care of preschool children with CF.
Role of NADPH oxidase-2 and oxidative stress in children exposed to passive smoking
Authors: Loffredo Lorenzo , Zicari Anna Maria , Occasi Francesca , Perri Ludovica , Carnevale Roberto , Angelico Francesco , Del Ben Maria , Martino Francesco , Nocella Cristina , De Castro Giovanna , Cammisotto Vittoria , Battaglia Simona , Duse Marzia , Violi Francesco 
Published: February 2018

This study explored oxidative stress, nicotinamide adenine dinucleotide phosphate oxidase-2 (Nox2) activity and endothelial function in children exposed or not to passive smoking. Compared with controls (n=57), Nox2 activity and isoprostanes were higher in children exposed to passive smoking (n=57); conversely, nitric oxide (NO) bioavailability and flow-mediated dilation were lower in children exposed to passive smoking. A bivariate analysis showed that Nox2 activity correlated with flow-mediated dilation, NO bioavailability and isoprostanes. A multivariate analysis showed that Nox2 activity was significantly associated with serum isoprostanes and cotinine levels; flow-mediated dilation was associated with isoprostanes and carotid intima-media thickness.In children exposed to passive smoking, Nox2-derived oxidative stress is upregulated and inversely associated with impaired artery dilation.
Parental overweight is associated with less encouragement of child dietary balance and variety and involvement in meal planning and preparation
Authors: Krystia Owen , Darlington Gerarda , Haines Jess , Ma David W.L. , Buchholz Andrea C. 
Published: February 2018

Little is known about how the body composition of parents of preschool-aged children is associated with their food parenting practices. In this study, we examined associations between parental body composition and food parenting practices in a sample of Canadian families with preschool-aged children. We conducted a cross-sectional analysis of 68 parents and 52 preschool-aged children. Measures included height, weight, waist circumference (WC), and percentage of fat mass (%FM) measured by BOD POD™. Parents completed an adapted version of the Comprehensive Feeding Practices Questionnaire. To account for correlated observations within families, we used generalized estimating equations with linear regression modelling to examine associations between parent body composition and food parenting practices, with child body mass index (BMI) z-score, child sex, parental sex, and family household income entered as covariates in all models. Parent BMI, WC, and %FM were each significantly and inversely associated with the encouragement of a balanced diet ([Formula: see text] = −0.021, p = 0.006; [Formula: see text] = −0.007, p = 0.038; [Formula: see text] = −0.010, p = 0.034, respectively) and child involvement in meal planning and preparation ([Formula: see text] = −0.082, p = 0.002; [Formula: see text] = −0.025, p = 0.032; [Formula: see text] = −0.038, p = 0.049, respectively). We provide preliminary evidence that overweight/obesity may be associated with select food parenting practices in Canadian families with preschool-age children. Parental body composition may be an important consideration in intervention strategies that target food parenting practices.
Early versus late cardiac remodeling during right ventricular pressure load and impact of preventive versus rescue therapy with endothelin-1 receptor blockers
Authors: Ramos Sara Roldan , Pieles Guido , Sun Mei , Slorach Cameron , Hui Wei , Friedberg Mark K. 
Published: February 2018

Pulmonary artery banding (PAB) causes right ventricular (RV) dysfunction, biventricular fibrosis, and apoptosis, which are attenuated by endothelin-1 receptor blockade (ERB). Little is known about the time course of remodeling and whether early versus late ERB confers improved outcome. PAB was performed in five groups of rabbits: Shams, 3-wk PAB (3W), 6-wk PAB (6W), 6-wk PAB + ERB administered from day 1 (6WERB1), and 6-wk PAB + ERB administered from day 21 (6WERB21). Biventricular development of profibrotic molecular signaling, fibrosis, apoptosis, and conductance catheter and echocardiography function were studied. Thirty-three rabbits [ n = 6–7 per group; 3.00 (0.23) kg, mean (SD)] developed half to full systemic RV pressures. Biventricular profibrotic signaling and collagen deposition [RV collagen: Shams 3.8 (0.58) vs. 3W 8.69 (2.52) vs. 6W 8.83 (4.02)%, P < 0.005] and apoptosis [RV: Shams 8.32 (3.2) vs. 3W 55.95 (47.55) vs. 6W 38.85 (17.26) apoptotic cells per microfield, P < 0.0005] increased with PAB. Early and late ERB attenuated fibrosis [RV: 6WERB1 5.55 (1.18), 6WERB21 5.63 (0.72)%] and apoptosis [RV: 6WERB1 11.1 (5.25), 6WERB21 20.24 (7.16) apoptotic cells per microfield, P < 0.0001 vs. 6W]. RV dimensions progressively increased at 3W and 6W and decreased with early ERB [end-diastolic dimensions: Shams 0.4 (0.13) vs. 3W 0.55 (0.78) vs. 6W 0.78 (0.25) vs. 6WERB1 0.71 (0.26) vs. 6WERB21 0.49 (0.23) cm, P < 0.05]. Despite increased RV contractility with PAB [RV end-systolic pressure-volume relationship: Shams 3.76 (1.76) vs. 3W 12.21 (3.44) vs. 6W 19.4 (6.88) mmHg/ml], biventricular function and cardiac output [Shams 196.1 (39.73) vs. 3W 149.9 (34.82) vs. 6W 151 (31.69) ml/min] worsened in PAB groups and improved with early and late ERB [6WERB1 202.8 (26.8), 6WERB21 194.8 (36.93) ml/min, P < 0.05 vs. PAB]. In conclusion, RV pressure overload induces early biventricular fibrosis, apoptosis, remodeling, and dysfunction that worsens with persistent RV hypertension. This remodeling is attenuated by early and late ERB. NEW & NOTEWORTHY Our results in a rabbit model of progressive right ventricular (RV) pressure loading indicate that biventricular fibrosis, apoptosis, and dysfunction are already present when RV hypertension is reached at 3 wk of progressive pulmonary artery banding. These findings worsen with persistent RV hypertension to 6 wk and are attenuated with both early and late endothelin-1 receptor blockade, with some advantages to early therapy. These findings highlight the role of endothelin-1 in driving biventricular remodeling secondary to RV hypertension and suggest that early therapy with an endothelin-1 receptor blocker may be beneficial in attenuating biventricular remodeling but that late therapy is also effective.
Abstract BS1-2: Myeloid-derived suppressor cells: many facets of regulation of tumor progression
Authors: Gabrilovich DI 
Published: February 2018

Abstract
Tumor associated macrophages (TAM), myeloid derived suppressor cells (MDSC), represented by PMN-MDSC and M-MDSC, and dendritic cells (DC) are major components of tumor microenvironment playing critical role in tumor progression. There are now compelling evidence linking MDSC with negative clinical outcomes in many types of cancer. Therefore, these cells are attractive therapeutic targets. Recently, several therapeutic strategies have been developed that target MDSC in mouse animal models and in first clinical trials. Recent findings of selective targeting of MDSC in cancer patients using agonistic TRAIL receptor DR5 antibody will be discussed. In 16 patients with advanced solid tumors this antibody demonstrated selective depletion of MDSC without affecting populations of neutrophils, monocytes, or lymphocytes. Another therapeutic strategy involves histone deacetilase inhibitor – entinostat. Recent study in tumor-bearing mice revealed that entinostat slightly increased expansion and accumulation of granulocytic cells in tumors. However, in contrast to untreated mice, these cells lacked suppressive activity. This effect was associated with potent antitumor activity of combination of entinostat with check-point inhibitors. By studying the effect of CSF1R inhibitor in tumor-bearing mice we identified the complex network regulating different groups of myeloid cells in tumor microenvironment. This network involves tumor cells and cancer associated fibroblast and protect tumors from loss of individual component of myeloid cell compartment. We determined that this network is operational not only in mice but also in cancer patients. Targeting of this network dramatically enhance the effect of cancer therapy.
Citation Format: Gabrilovich DI. Myeloid-derived suppressor cells: many facets of regulation of tumor progression [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr BS1-2.