bluuebunny/crossref_metadata_2025_split huggingface dataset:
The SAT Protein of Porcine Parvovirus Accelerates Viral Spreading through Induction of Irreversible Endoplasmic Reticulum Stress
Authors: Mészáros István , Tóth Renáta , Olasz Ferenc , Tijssen Peter , Zádori Zoltán 
Published: June 2017

ABSTRACT

The SAT protein (SATp) of porcine parvovirus (PPV) accumulates in the endoplasmic reticulum (ER), and SAT deletion induces the slow-spreading phenotype. The
in vitro
comparison of the wild-type Kresse strain and its SAT knockout (SAT
−
) mutant revealed that prolonged cell integrity and late viral release are responsible for the slower spreading of the SAT
−
virus. During PPV infection, regardless of the presence or absence of SATp, the expression of downstream ER stress response proteins (Xbp1 and CHOP) was induced. However, in the absence of SATp, significant differences in the quantity and the localization of CHOP were detected, suggesting a role of SATp in the induction of irreversible ER stress in infected cells. The involvement of the induction of irreversible ER stress in porcine testis (PT) cell necrosis and viral egress was confirmed by treatment of infected cells by ER stress-inducing chemicals (MG132, dithiothreitol, and thapsigargin), which accelerated the egress and spreading of both the wild-type and the SAT
−
viruses. UV stress induction had no beneficial effect on PPV infection, underscoring the specificity of ER stress pathways in the process. However, induction of CHOP and its nuclear translocation cannot alone be responsible for the biological effect of SAT, since nuclear CHOP could not complement the lack of SAT in a coexpression experiment.

IMPORTANCE
SATp is encoded by an alternative open reading frame of the PPV genome. Earlier we showed that SATp of the attenuated PPV NADL-2 strain accumulates in the ER and accelerates virus release and spreading. Our present work revealed that slow spreading is a general feature of SAT
−
PPVs and is the consequence of prolonged cell integrity. PPV infection induced ER stress in infected cells regardless of the presence of SATp, as demonstrated by the morphological changes of the ER and expression of the stress response proteins Xbp1 and CHOP. However, the presence of SATp made the ER stress more severe and accelerated cell death during infection, as shown by the higher rate of expression of CHOP and alteration of the localization of CHOP. The beneficial effect of irreversible ER stress on PPV spread was confirmed by treatment of infected cells with ER stress-inducing chemicals.
Seneca Valley Virus Suppresses Host Type I Interferon Production by Targeting Adaptor Proteins MAVS, TRIF, and TANK for Cleavage
Authors: Qian Suhong , Fan Wenchun , Liu Tingting , Wu Mengge , Zhang Huawei , Cui Xiaofang , Zhou Yun , Hu Junjie , Wei Shaozhong , Chen Huanchun , Li Xiangmin , Qian Ping 
Published: June 2017

ABSTRACT

Seneca Valley virus (SVV) is an oncolytic RNA virus belonging to the
Picornaviridae
family. Its nucleotide sequence is highly similar to those of members of the
Cardiovirus
genus. SVV is also a neuroendocrine cancer-selective oncolytic picornavirus that can be used for anticancer therapy. However, the interaction between SVV and its host is yet to be fully characterized. In this study, SVV inhibited antiviral type I interferon (IFN) responses by targeting different host adaptors, including mitochondrial antiviral signaling (MAVS), Toll/interleukin 1 (IL-1) receptor domain-containing adaptor inducing IFN-β (TRIF), and TRAF family member-associated NF-κB activator (TANK), via viral 3C protease (3C
pro
). SVV 3C
pro
mediated the cleavage of MAVS, TRIF, and TANK at specific sites, which required its protease activity. The cleaved MAVS, TRIF, and TANK lost the ability to regulate pattern recognition receptor (PRR)-mediated IFN production. The cleavage of TANK also facilitated TRAF6-induced NF-κB activation. SVV was also found to be sensitive to IFN-β. Therefore, SVV suppressed antiviral IFN production to escape host antiviral innate immune responses by cleaving host adaptor molecules.

IMPORTANCE
Host cells have developed various defenses against microbial pathogen infection. The production of IFN is the first line of defense against microbial infection. However, viruses have evolved many strategies to disrupt this host defense. SVV, a member of the
Picornavirus
genus, is an oncolytic virus that shows potential functions in anticancer therapy. It has been demonstrated that IFN can be used in anticancer therapy for certain tumors. However, the relationship between oncolytic virus and innate immune response in anticancer therapy is still not well known. In this study, we showed that SVV has evolved as an effective mechanism to inhibit host type I IFN production by using its 3C
pro
to cleave the molecules MAVS, TRIF, and TANK directly. These molecules are crucial for the Toll-like receptor 3 (TLR3)-mediated and retinoic acid-inducible gene I (RIG-I)-like receptor (RLR)-mediated signaling pathway. We also found that SVV is sensitive to IFN-β. These findings increase our understanding of the interaction between SVV and host innate immunity.
Importance and added value of functional impairment to predict mortality: a cohort study in Swedish medical inpatients
Authors: Torisson Gustav , Stavenow Lars , Minthon Lennart , Londos Elisabet 
Published: June 2017

BackgroundAccurate estimation of prognosis in multimorbid hospital patients could improve quality of care. This study aims to determine the relative importance and added value of a performance-based activities of daily living (ADL) measure with regard to mortality prediction.Methods200 inpatients, aged over 60 years, were recruited at the Department of General Internal Medicine at a tertiary university hospital. Two nested survival models were built, one with established risk factors (age, sex, Charlson comorbidity index, haemoglobin, albumin, body mass index and glomerular filtration rate), and one using the same covariates with the Gottfries-Bråne-Steen (GBS)-ADL measure added. The relative importance of GBS-ADL was evaluated in the full model. The added value of GBS-ADL was determined by comparing the nested models using four approaches: difference in overall χ2, discrimination, continuous net reclassification index (NRI >0) and integrated discrimination improvement (IDI).ResultsIn the full model, GBS-ADL was the single most important predictor of mortality (χ2-df=30, p<0.001). The likelihood ratio χ2test showed significant added value of ADL (p<0.001). The C-statistic was 0.78 with ADL and 0.72 without (difference 0.058, 95% CI 0.022 to 0.094). The NRI >0 was 0.42 (95% CI 0.20 to 0.58) and IDI 0.15 (95% CI 0.07 to 0.22).ConclusionsCompared with a set of available clinical risk factors, impairment in ADL was a stronger predictor of all-cause mortality, showing substantial added value. Implementing quantitative ADL measurements could enable more appropriate and individual care for the elderly.
Double burden or double counting of child malnutrition? The methodological and theoretical implications of stuntingoverweight in low and middle income countries
Authors: Bates Katie , Gjonça Arjan , Leone Tiziana 
Published: June 2017

BackgroundThere is increasing concern at research and policy levels about the double burden of child malnutrition (DBCM)—with stunting and overweight found across different groups of children. Despite some case studies suggesting that stunting and overweight can occur concurrently in children, here known as ‘stuntingoverweight’, and major drives to reduce all forms of malnutrition in low and middle income countries (LMICs), stuntingoverweight is continually overlooked. This research evidences the prevalence of stuntingoverweight across LMICs, exploring the theoretical and methodological implications of failing to acknowledge this form of malnutrition.MethodsPrevalence estimates of stuntingoverweight are constructed from 79 LMICs with nationally representative anthropometric survey data. Stunting and overweight estimates are amended to exclude stuntedoverweight children. These estimates are compared with those published in the Joint Child Malnutrition Estimates (JMEs)—evidencing overestimation and double counting of stuntedoverweight children.ResultsChildren can be concurrently stunted and overweight. Stuntedoverweight children are found in all LMICs, from 0.3% to 11.7% of under-fives and are included in both stunting and overweight rates. Analysed together, this leads to double counting of stuntedoverweight children. This artificial inflation of stunting and overweight rates can give a false impression of a DBCM, obscuring the true diversity of malnutrition present. Over 10 million children are stuntedoverweight in the world.ConclusionsStuntingoverweight is a newly recognised, understudied phenomenon. Affected children are included in both stunting and overweight prevalence estimates, introducing unobserved heterogeneity to both individual-level and population-level research and double counting to population-level research. Overlooking stuntedoverweight children has great implications for methodology, theory, policies, programmes and the health of affected children.
Effect of SiC particle size on the microstructure and properties of cold-sprayed Al/SiCp composite coating
Authors: Yu Min , Hua Junwei 
Published: June 2017

The Al5056/SiC composite coatings were prepared by cold spraying. Experimental results show that the SiC content in the composite coating deposited with the SiC powder having an average size of 67 [Formula: see text]m (Al5056/SiC-67) is similar to that deposited with the SiC powder having an average size of 27 [Formula: see text]m (Al5056/SiC-27). The microhardness and cohesion strength of Al5056/SiC-67 coating are higher than those of the Al5056/SiC-27 coating. In addition, the Al5056/SiC-67 coating having a superior wear resistance because of the coarse SiC powder with a superior kinetic energy contributes to the deformation resistance of the matrix Al5056 particles.
The Effect of the Degree of Astigmatism on Optical Quality in Children
Authors: Gao Jing , Wang Xiao-xia , Wang Lin , Sun Yuan , Liu Rui-fen , Zhao Qi 
Published: June 2017

Purpose. To investigate the effect of the degree of astigmatism on optical quality in children. The important objective evaluation parameters we focus on include the RMS of the high-order aberrations, MTF, and PSF. Methods. The children, age ranging from 7 to 10 years old, underwent an optometry examination. Fifty-nine children who met the inclusion criteria were divided into three groups: A (1.0 D ≤ astigmatism < 2.0 D), B (2.0 D ≤ astigmatism < 3.0 D), and C (3.0 D ≤ astigmatism < 4.0 D). The OPD-SCAN-III aberrometer was used to measure PSF, MTF, and other optical parameters. Total higher-order aberrations, total coma aberrations, total spherical aberrations, and total trefoil aberrations corresponding to the RMS value, the AR value of MTF, and the SR value of PSF with a 4 mm pupil diameter were assessed. Results. RMS-HO, RMS-T.Coma, RMS-T.Tre, and RMS-T.Sph in the three groups were significantly increased with increasing the degree of astigmatism, while there were no significant differences in RMS-T.Sph between the groups. The AR value and the SR value decreased with increasing degree of astigmatism, and there were significant differences in the AR value and the SR value. Conclusion. Astigmatism has a significant influence on the higher-order aberrations, MTF, and PSF in the children. The effect of astigmatism value on the optical quality is mainly reflected in the change in these three parameters.
Mutational Signatures in Breast Cancer: The Problem at the DNA Level
Authors: Nik-Zainal Serena , Morganella Sandro 
Published: June 2017

AbstractA breast cancer genome is a record of the historic mutagenic activity that has occurred throughout the development of the tumor. Indeed, every mutation may be informative. Although driver mutations were the main focus of cancer research for a long time, passenger mutational signatures, the imprints of DNA damage and DNA repair processes that have been operative during tumorigenesis, are also biologically illuminating. This review is a chronicle of how the concept of mutational signatures arose and brings the reader up-to-date on this field, particularly in breast cancer. Mutational signatures have now been advanced to include mutational processes that involve rearrangements, and novel cancer biological insights have been gained through studying these in great detail. Furthermore, there are efforts to take this field into the clinical sphere. If validated, mutational signatures could thus form an additional weapon in the arsenal of cancer precision diagnostics and therapeutic stratification in the modern war against cancer. Clin Cancer Res; 23(11); 2617–29. ©2017 AACR.See all articles in this CCR Focus section, “Breast Cancer Research: From Base Pairs to Populations.”
Pediatric Cancer Predisposition Imaging: Focus on Whole-Body MRI
Authors: Greer Mary-Louise C. , Voss Stephan D. , States Lisa J. 
Published: June 2017

Abstract
The American Association for Cancer Research convened a meeting of international pediatric oncologists, geneticists, genetic counselors, and radiologists expert in childhood cancer predisposition syndromes (CPS) in October 2016 to propose consensus surveillance guidelines. Imaging plays a central role in surveillance for most, though not all, syndromes discussed. While encompassing the full gamut of modalities, there is increasing emphasis on use of nonionizing radiation imaging options such as magnetic resonance imaging (MRI) in children and adolescents, especially in the pediatric CPS population. In view of rapid evolution and widespread adoption of whole-body MRI (WBMRI), the purpose of our review is to address WBMRI in detail. We discuss its place in the surveillance of a range of pediatric CPS, the technical and logistical aspects of acquiring and interpreting these studies, and the inherent limitations of WBMRI. We also address issues associated with sedation and use of gadolinium-based contrast agents in MRI in children. Clin Cancer Res; 23(11); e6–e13. ©2017 AACR.
See all articles in the online-only CCR Pediatric Oncology Series.
In Vivo Antitumoral Efficacy of PhAc-ALGP-Doxorubicin, an Enzyme-Activated Doxorubicin Prodrug, in Patient-Derived Soft Tissue Sarcoma Xenograft Models
Authors: Cornillie Jasmien , Wozniak Agnieszka , Pokreisz Peter , Casazza Andrea , Vreys Lise , Wellens Jasmien , Vanleeuw Ulla , Gebreyohannes Yemarshet K. , Debiec-Rychter Maria , Sciot Raf , Hompes Daphne , Schöffski Patrick 
Published: June 2017

Abstract
Given the very limited efficacy of doxorubicin (doxo) in soft tissue sarcoma, there is a clear need for more active and less toxic treatments for this family of diseases. However, due to the rarity of these malignancies and lack of reliable preclinical models, development of new therapies has lagged behind. We evaluated the efficacy of PhAc-ALGP-doxorubicin (ALGP-doxo), a prodrug metabolized to doxo by peptidases present in tumor cells and/or tumor microenvironment, in a synovial sarcoma (SynSa) and two dedifferentiated liposarcoma (DDLPS) patient-derived xenograft models. Sixty-eight mice were engrafted bilaterally with human DDLPS or SynSa and randomized to control, doxo, or ALGP-doxo treatment, which were administered using an intraperitoneal minipump. Tumor volume measurement, histopathology, and Western blotting were used to assess treatment efficacy. Tumor regrowth was evaluated in a subset of mice over a period of 2 weeks after treatment cessation. Although tumor volume in the control and doxo groups increased steadily, ALGP-doxo caused tumor volume stabilization in the DDLPS xenografts and significant tumor shrinkage in the SynSa model, continuing after treatment cessation. A significant decrease in proliferation and increase in apoptosis compared with control and doxo was observed during and after treatment with ALGP-doxo in all models. In conclusion, ALGP-doxo shows considerably higher antitumoral efficacy compared with doxo in all patient-derived xenograft models tested. Administration of a 30- to 40-fold higher dose of ALGP-doxo than doxo is tolerated without significant adverse events. These results warrant further testing of this prodrug in anthracycline-sensitive and -resistant models of soft tissue sarcoma. Mol Cancer Ther; 16(8); 1566–75. ©2017 AACR.
Thrombin is a selective inducer of heparanase release from platelets and granulocytes via protease-activated receptor-1
Authors: Tatour Mifleh , Shapira Ma'anit , Axelman Elena , Ghanem Shourouk , Keren-Politansky Anat , Bonstein Lilach , Brenner Benjamin , Nadir Yona 
Published: June 2017

SummaryHeparanase, known to be involved in angiogenesis and metastasis, was shown to form a complex with tissue factor (TF) and to enhance the generation of factor Xa. Platelets and granulocytes contain abundant amounts of heparanase that may enhance the coagulation system upon discharge. It was the aim of this study to identify the inducer and pathway of heparanase release from these cells. Platelets and granulocytes were purified from pooled normal plasma and were incubated with ATP, ADP, epinephrine, collagen, ristocetin, arachidonic acid, serotonin, LPS and thrombin. Heparanase levels were assessed by ELISA, heparanase procoagulant activity assay and western blot analysis. The effects of selective protease-activated receptor (PAR)-1 and 2 inhibitors and PAR-1 and 4 activators were studied. An in-house synthesised inhibitory peptide to heparanase was used to evaluate platelet heparanase involvement in activation of the coagulation system. Heparanase was released from platelets only by thrombin induction while other inducers exerted no such effect. The heparanase level in a platelet was found to be 40 % higher than in a granulocyte. Heparanase released from platelets or granulocytes increased factor Xa generation by three-fold. PAR-1 activation via ERK intracellular pathway was found to induce heparanase release. In conclusion, heparanase is selectively released from platelets and granulocytes by thrombin interacting with PAR-1. Heparanase derived from platelets and granulocytes is involved in activation of the extrinsic coagulation pathway. The present study implies on a potential anticoagulant effect, in addition to anti-platelet effect, of the new clinically studied PAR-1 inhibitors.
Effect of Coronary Revascularization on the Prognostic Value of Stress Myocardial Contrast Wall Motion and Perfusion Imaging
Authors: Gaibazzi Nicola , Porter Thomas , Lorenzoni Valentina , Pontone Gianluca , De Santis Delia , De Rosa Andrea , Guaricci Andrea Igoren 
Published: June 2017

Background

The assessment of myocardial perfusion (
MP
) and wall motion (
WM
) using contrast dipyridamole echocardiography (
cSE
‐
WMP
) improves the sensitivity to detect coronary artery disease and the stratification of cardiac events, but its long‐term value for fatal and nonfatal ischemic cardiac events, also with respect to patients undergoing revascularization or not, remains to be determined.

Methods and Results

One‐thousand three‐hundred and twenty‐nine patients with suspect or known CAD who underwent
cSE
‐
WMP
were followed for a median 5.5 years. The independent prognostic value of
cSE
‐
WMP
regarding cardiac death or nonfatal myocardial infarction was related to stress
WM
and
MP
, rest ejection fraction, clinical risk factors, and medications. Patients revascularized after
cSE
‐
WMP
were separately analyzed to determine whether the procedure influenced outcome and whether this depends on
cSE
‐
WMP
results. A total of 125 cardiac fatal and nonfatal ischemic events (9.4%) occurred during the follow‐up (61 deaths, 64 myocardial infarctions). The 5‐year event rate with normal
MP
and
WM
was 5.9%, 9.9% with isolated
MP
defects (normal
WM
), and 15.5% with both
MP
and
WM
abnormalities. In patients not undergoing revascularization (n=1111), reversible
MP
defects added discrimination value over
WM
response and clinical factors/medication data (
P
=0.001), while in the cohort undergoing revascularization (n=218),
cSE
‐
WMP
results did not influence outcome.

Conclusions

cSE
‐
WMP
, with both contrast
MP
and
WM
assessments, provides independent, incremental prognostic information regarding ischemic cardiac events at 5 years in patients with known or suspected coronary artery disease. Revascularization reduces cardiac events after an abnormal
cSE
‐
WMP
, resulting in outcomes not different from those in patients with normal
cSE
‐WMP.
Further Thoughts on the Syntax of Il. 5.265-269
Authors: Willi Andreas 
Published: June 2017

AbstractIn response to a recent article by P. Probert on the same passage, it is argued that we need not assume that Il. 5.265-269 obliquely refers to an otherwise unknown ‘stud farm’ of Zeus if we want to maintain that the phenomenon of attractio relativi is only attested in post-Homeric times. The relative pronoun ἧς on which Probert’s reading is based should rather be understood as representing either a ‘descriptive’ genitive or, even more likely, an early instance of the genitive of price.
Sexual minority youth and depressive symptoms or depressive disorder: A systematic review and meta-analysis of population-based studies
Authors: Lucassen Mathijs FG , Stasiak Karolina , Samra Rajvinder , Frampton Christopher MA , Merry Sally N 
Published: June 2017

Objective: Research has suggested that sexual minority young people are more likely to have depressive symptoms or depressive disorder, but to date most studies in the field have relied on convenience-based samples. This study overcomes this limitation by systematically reviewing the literature from population-based studies and conducting a meta-analysis to identify whether depressive disorder and depressive symptoms are elevated in sexual minority youth. Method: A systematic review and meta-analysis were conducted and informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement to determine if rates of depressive symptoms or depressive disorder differ for sexual minority youth, relative to heterosexual adolescents. MEDLINE, PsycINFO, EMBASE and ERIC databases were searched. Studies reporting depressive symptom data or the prevalence of depressive disorder in population-based samples of adolescents, which included sexual minority youth and heterosexual young people, were included in the review. A meta-analysis was conducted to examine differences between groups. Results: Twenty-three articles met the inclusion criteria. The proportion of sexual minority youth in the studies ranged from 2.3% to 12%. Sexual minority youth reported higher rates of depressive symptoms and depressive disorder (odds ratio = 2.94, p < 0.001 and standardized mean difference, d = 0.39, p < 0.001) in comparison to heterosexual young people. Female sexual minority youth were more likely to report depressive symptoms when compared to male sexual minority youth (standardized mean difference, d = 0.34, p < 0.001). Limitations included variations in how sexuality was operationalized and how depressive symptoms or depressive disorder was measured. Conclusions: There is robust evidence that rates of depressive disorder and depressive symptoms are elevated in sexual minority youth in comparison to heterosexual young people. Despite the elevated risk of depressive symptoms or depressive disorder for sexual minority youth, the treatment for this group of young people has received little attention.