bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Papillomavirus Major Capsid Protein L1 Remains Associated with the Incoming Viral Genome throughout the Entry Process
Authors: DiGiuseppe Stephen , Bienkowska-Haba Malgorzata , Guion Lucile G. M. , Keiffer Timothy R. , Sapp Martin
Published: June 2017

During infectious entry, acidification within the endosome triggers uncoating of the human papillomavirus (HPV) capsid, whereupon host cyclophilins facilitate the release of most of the major capsid protein, L1, from the minor capsid protein L2 and the viral genome. The L2/DNA complex traffics to the
trans
-Golgi network (TGN). After the onset of mitosis, HPV-harboring transport vesicles bud from the TGN, followed by association with mitotic chromosomes. During this time, the HPV genome remains in a vesicular compartment until the nucleus has completely reformed. Recent data suggest that while most of L1 protein dissociates and is degraded in the endosome, some L1 protein remains associated with the viral genome. The L1 protein has DNA binding activity, and the L2 protein has multiple domains capable of interacting with L1 capsomeres. In this study, we report that some L1 protein traffics with L2 and viral genome to the nucleus. The accompanying L1 protein is mostly full length and retains conformation-dependent epitopes, which are recognized by neutralizing antibodies. Since more than one L1 molecule contributes to these epitopes and requires assembly into capsomeres, we propose that L1 protein is present in the form of pentamers. Furthermore, we provide evidence that the L1 protein interacts directly with viral DNA within the capsid. Based on our findings, we propose that the L1 protein, likely arranged as capsomeres, stabilizes the viral genome within the subviral complex during intracellular trafficking.

IMPORTANCE
After internalization, the nonenveloped human papillomavirus virion uncoats in the endosome, whereupon conformational changes result in a dissociation of a subset of the major capsid protein L1 from the minor capsid protein L2, which remains in complex with the viral DNA. Recent data suggest that some L1 protein may accompany the viral genome beyond the endosomal compartment. We demonstrate that conformationally intact L1 protein, likely still arranged as capsomeres, remains associated with the incoming viral genome throughout mitosis and transiently resides in the nucleus until after the viral DNA is released from the transport vesicle.
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

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

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

Background

Accurate 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.

Methods

200 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).

Results

In 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).

Conclusions

Compared 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

Background

There 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.

Methods

Prevalence 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.

Results

Children 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.

Conclusions

Stuntingoverweight 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.
Methodology to reliably measure preventable trauma death rate
Authors: Drake Stacy A , Wolf Dwayne A , Meininger Janet C , Cron Stanley G , Reynold Thomas , Wade Charles E , Holcomb John B
Published: June 2017

This article describes a methodology to establish a trauma preventable death rate (PDR) in a densely populated county in the USA. Harris County has >4 million residents, encompasses a geographic area of 1777 square miles and includes the City of Houston, Texas. Although attempts have been made to address a national PDR, these studies had significant methodological flaws. There is no national consensus among varying groups of clinicians for defining preventability or documenting methods by which preventability is determined. Furthermore, although trauma centers routinely evaluate deaths within their hospital for preventability, few centers compare across regions, within the prehospital arena and even fewer have evaluated trauma deaths at non-trauma centers. Comprehensive population-based data on all trauma deaths within a defined region would provide a framework for effective prevention and intervention efforts at the regional and national levels. The authors adapted a military method recently used in Southwest Asia to determine the potential preventability of civilian trauma deaths occurring across a large and diverse population. The project design will allow a data-driven approach to improve services across the entire spectrum of trauma care, from prevention through rehabilitation.
Explaining electric conductivity using the particle-in-a-box model: quantum superposition is the key
Authors: Sivanesan Umaseh , Tsang Kin , Izmaylov Artur F.
Published: June 2017

Most of the textbooks explaining electric conductivity in the context of quantum mechanics provide either incomplete or semi-classical explanations that are not connected with the elementary concepts of quantum mechanics. We explain electric conductivity using the simplest model system in quantum mechanics, a particle in a box (PIB). To stimulate the particle dynamics, a linear potential tilting the bottom of the box is introduced, which is equivalent to imposing a constant electric field for a charged particle. Although the PIB model represents a closed system that cannot have a flow of electrons through it, we consider the oscillatory dynamics of the particle probability density as the analogue of the electric current. Relating the amplitude and other parameters of the particle oscillatory dynamics with the gap between the ground and excited states of the PIB model allows us to demonstrate one of the most basic dependencies of electric conductivity on the valence–conduction band gap of the material.
Quantum chaos inside black holes
Authors: Addazi Andrea
Published: June 2017

We show how semiclassical black holes can be reinterpreted as an effective geometry, composed of a large ensemble of horizonless naked singularities (eventually smoothed at the Planck scale). We call these new items frizzy-balls, which can be rigorously defined by Euclidean path integral approach. This leads to interesting implications about information paradoxes. We demonstrate that infalling information will chaotically propagate inside this system before going to the full quantum gravity regime (Planck scale).
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.
Infinite symmetric group, pseudomanifolds, and combinatorial cobordism-like structures
Authors: Gaifullin Alexander A. , Neretin Yury A.
Published: June 2017

We consider a category [Formula: see text] whose morphisms are [Formula: see text]-dimensional pseudomanifolds equipped with certain additional structures (coloring and labeling of some cells), multiplication of morphisms is similar to a concatenation of cobordisms. On the other hand, we consider the product [Formula: see text] of [Formula: see text] copies of infinite symmetric group. We construct a correspondence between the sets of morphisms of [Formula: see text] and double coset spaces of [Formula: see text] with respect to certain subgroups. We show that unitary representations of [Formula: see text] produce functors from the category of [Formula: see text] to the category of Hilbert spaces and bounded linear operators.
Farrell–Jones via Dehn fillings
Authors: Antolín Yago , Coulon Rémi , Gandini Giovanni
Published: June 2017

Following the approach of Dahmani, Guirardel and Osin, we extend the group theoretical Dehn filling theorem to show that the pre-images of infinite order subgroups have a certain structure of a free product. We then apply this result to establish the Farrell–Jones conjecture for groups hyperbolic relative to a family of residually finite subgroups satisfying the Farrell–Jones conjecture, partially recovering a result of Bartels.
Design and characterization of three-dimensional twist-braid scaffolds for anterior cruciate ligament regeneration
Authors: Madhavarapu Shreya , Rao Rohit , Libring Sarah , Fleisher Emma , Yankannah Yasonia , Freeman Joseph W.
Published: June 2017

The anterior cruciate ligament (ACL) is the most commonly injured ligament in the knee, with more than 350,000 ACL injuries reported annually in the US. Current treatments include the use of autografts and allografts, which have a number of disadvantages. Previous attempts to use synthetic materials in ligament replacement have been unsuccessful due to their inability to replicate the long-term mechanical properties of the native ligament. The focus of this study was to develop twist-braid poly(L-lactic acid) (PLLA) scaffolds for ACL regeneration. Poly(ethylene glycol) diacrylate (PEGDA) was incorporated into the twist-braid scaffolds to evaluate its impact on their mechanical behavior. The twist-braid scaffolds were also compared with braided scaffolds. Scaffold mechanical properties were evaluated based on stress-relaxation, tensile and fatigue properties of the braided-only, twist-braid, and the twist-braid scaffolds with PEGDA. All the scaffolds exhibited properties comparable to the native human ACL with the twist-braid scaffolds displaying resistance to fatigue. Scaffolds were seeded with rat patellar tendon fibroblasts. Cell viability and the amount of protein released were studied over a course of 8 weeks. The scaffolds were stained with Picrosirius red after 8 weeks to show the deposition of extracellular matrix by the cells. The results from this study showed that the twist-braid scaffolds have properties most suitable for ligament regeneration.
The activation of N-methyl-d-aspartate receptors downregulates transient outward potassium and L-type calcium currents in rat models of depression
Authors: Liu Xin , Shi Shaobo , Yang Hongjie , Qu Chuan , Chen Yuting , Liang Jinjun , Yang Bo
Published: June 2017

Major depression is an important clinical factor in ventricular arrhythmia. Patients diagnosed with major depression overexpress N-methyl-d-aspartate receptors (NMDARs). Previous studies found that chronic NMDAR activation increases susceptibility to ventricular arrhythmias. We aimed to explore the mechanisms by which NMDAR activation may increase susceptibility to ventricular arrhythmias. Male rats were randomly assigned to either normal environments as control (CTL) group or 4 wk of chronic mild stress (CMS) to produce a major depression disorder (MDD) model group. After 4 wk of CMS, depression-like behaviors were measured in both groups. Varying doses (1–100 μM) of NMDA and 10 μM NMDA antagonist (MK-801) were perfused through ventricular myocytes isolated from MDD rats to measure the L-type calcium current ( ICa-L) and transient outward potassium current ( Ito). Structural remodeling was assessed using serial histopathology including Masson’s trichrome dye. Electrophysiological characteristics were evaluated using Langendorff perfusion. Depression-like behaviors were observed in MDD rats. MDD rats showed longer action potential durations at 90% repolarization and higher susceptibility to ventricular arrhythmias than CTL rats. MDD rats showed lower ICa-L and Ito current densities than CTL rats. Additionally, NMDA reduced both currents in a concentration-dependent manner, whereas there was no significant impact on the currents when perfused with MK-801. MDD rats exhibited significantly more fibrosis areas in heart tissue and reduced expression of Kv4.2, Kv4.3, and Cav1.2. We observed that acute NMDAR activation led to downregulation of potassium and L-type calcium currents in a rat model of depression, which may be the mechanism underlying ventricular arrhythmia promotion by depression.
Development and aging of human spinal cord circuitries
Authors: Geertsen Svend Sparre , Willerslev-Olsen Maria , Lorentzen Jakob , Nielsen Jens Bo
Published: June 2017

The neural motor circuitries in the spinal cord receive information from our senses and the rest of the nervous system and translate it into purposeful movements, which allow us to interact with the rest of the world. In this review, we discuss how these circuitries are established during early development and the extent to which they are shaped according to the demands of the body that they control and the environment with which the body has to interact. We also discuss how aging processes and physiological changes in our body are reflected in adaptations of activity in the spinal cord motor circuitries. The complex, multifaceted connectivity of the spinal cord motor circuitries allows them to generate vastly different movements and to adapt their activity to meet new challenges imposed by bodily changes or a changing environment. There are thus plenty of possibilities for adaptive changes in the spinal motor circuitries both early and late in life.
Role of the Immune System in Hypertension
Authors: Rodriguez-Iturbe Bernardo , Pons Hector , Johnson Richard J.
Published: June 2017

High blood pressure is present in more than one billion adults worldwide and is the most important modifiable risk factor of death resulting from cardiovascular disease. While many factors contribute to the pathogenesis of hypertension, a role of the immune system has been firmly established by a large number of investigations from many laboratories around the world. Immunosuppressive drugs and inhibition of individual cytokines prevent or ameliorate experimental hypertension, and studies in genetically-modified mouse strains have demonstrated that lymphocytes are necessary participants in the development of hypertension and in hypertensive organ injury. Furthermore, immune reactivity may be the driving force of hypertension in autoimmune diseases. Infiltration of immune cells, oxidative stress, and stimulation of the intrarenal angiotensin system are induced by activation of the innate and adaptive immunity. High blood pressure results from the combined effects of inflammation-induced impairment in the pressure natriuresis relationship, dysfunctional vascular relaxation, and overactivity of the sympathetic nervous system. Imbalances between proinflammatory effector responses and anti-inflammatory responses of regulatory T cells to a large extent determine the severity of inflammation. Experimental and human studies have uncovered autoantigens (isoketal-modified proteins and heat shock protein 70) of potential clinical relevance. Further investigations on the immune reactivity in hypertension may result in the identification of new strategies for the treatment of the disease.
No Significant Difference between Plasma miRNAs and Plasma-Derived Exosomal miRNAs from Healthy People
Authors: Tian Fei , Shen Yanting , Chen Zhenzhu , Li Rui , Ge Qinyu
Published: June 2017

Background. MicroRNAs (miRNAs) are small noncoding RNAs that are involved in many biological regulation processes. Studies have reported that miRNAs are enriched in human plasma and plasma-derived exosome as novel diagnostic biomarkers. The aim of this study was to determine whether the miRNA expression levels are different between plasma and plasma-derived exosome. Methods. We sequenced and quantified the miRNAs in plasma and exosome from healthy blood samples and validated three miRNAs in the two groups of lung cancer samples by qRT-PCR. Results. The sequencing results showed that only several of miRNAs were differential, while the qRT-PCR further validated that most of them did not have the consistent differences. However, the levels of two upregulated miRNAs (miR-181b-5p and miR-21-5p) in lung cancer were significantly higher in exosomes than plasma. Conclusions. To the best of our knowledge, this study is the first to compare the expression levels of miRNAs between plasma and exosome in healthy blood samples. Our data suggested that the miRNA levels were similar in the two parts of the healthy people, whereas the two onco-miRNAs were significantly enriched in the exosome of lung cancer patients.
Stereopsis, Visuospatial Ability, and Virtual Reality in Anatomy Learning
Authors: Luursema Jan-Maarten , Vorstenbosch Marc , Kooloos Jan
Published: June 2017

A new wave of virtual reality headsets has become available. A potential benefit for the study of human anatomy is the reintroduction of stereopsis and absolute size. We report a randomized controlled trial to assess the contribution of stereopsis to anatomy learning, for students of different visuospatial ability. Sixty-three participants engaged in a one-hour session including a study phase and posttest. One group studied 3D models of the anatomy of the deep neck in full stereoptic virtual reality; one group studied those structures in virtual reality without stereoptic depth. The control group experienced an unrelated virtual reality environment. A post hoc questionnaire explored cognitive load and problem solving strategies of the participants. We found no effect of condition on learning. Visuospatial ability however did impact correct answers at F(1)=5.63 and p=.02. No evidence was found for an impact of cognitive load on performance. Possibly, participants were able to solve the posttest items based on visuospatial information contained in the test items themselves. Additionally, the virtual anatomy may have been complex enough to discourage memory based strategies. It is important to control the amount of visuospatial information present in test items.
Chemical Separation on Silver Nanorods Surface Monitored by TOF-SIMS
Authors: Petruš Ondrej , Oriňak Andrej , Oriňaková Renáta , Muhmann Christian , Macko Ján , Hrdý Radim , Hubálek Jaromír , Erdelyi Branislav , Arlinghaus Heinrich F.
Published: June 2017

The article introduces a possible chemical separation of a mixture of two compounds on the metal nanorods surface. A silver nanorods surface has been prepared by controlled electrochemical deposition in anodic alumina oxide (AAO) template. Rhodamine 6G and 4-aminothiophenol have been directly applied to the sampling point on a silver nanorods surface in an aliquot mixture. The position of the resolved compounds was analysed by time-of-flight secondary ion mass spectrometry (TOF-SIMS) which measured the fragments and the molecular ions of the two compounds separated on the silver nanorods surface. Rhodamine 6G has been preconcentrated as 1.5 mm radial from the sampling point while 4-aminothiophenol formed a continuous self-assembled monolayer on the silver nanorods surface with a maximum molecular ion intensity at a distance of 0.5 mm from the sampling point. The separation of the single chemical components from the two-component mixture over the examined silver nanostructured films could clearly be shown. A fast separation on the mentioned nanotextured films was observed (within 50 s). This procedure can be easily integrated into the micro/nanofluidic systems or chips and different detection systems can be applied.
A Mass of Pancreatic and Gastric Heterotopia Causing a Small Bowel Obstruction in a 61-Year-Old Male
Authors: Alfrejat Majd , Khalil Bassem , Jackobs Jordan , Anderson William , Eschbacher Jennifer
Published: June 2017

Heterotopic tissue is a congenital anomaly that has been previously reported. Gastric and pancreatic heterotopia are among the most studied ones. Herein, we describe a case of a combined pancreatic and gastric heterotopia that formed a mass and caused a small intestine obstruction in a 61-year-old male. We also did a brief literature review of cases with gastric and pancreatic heterotopia in adult patients.
Quantitative and Qualitative Characterization of Gentiana rigescens Franch (Gentianaceae) on Different Parts and Cultivations Years by HPLC and FTIR Spectroscopy
Authors: Qi Lu-Ming , Zhang Ji , Zhao Yan-Li , Zuo Zhi-Tian , Jin Hang , Wang Yuan-Zhong
Published: June 2017

Gentiana rigescens Franch (Gentianaceae) is a famous medicinal plant for treatments of rheumatism, convulsion, and jaundice. Comprehensive investigation of different parts and cultivation years of this plant has not yet been conducted. This study presents the quantitative and qualitative characterization of iridoid glycosides from G. rigescens performed by HPLC and FTIR spectroscopy techniques. The accumulations of loganic acid, swertiamarin, gentiopicroside, and sweroside were determined. Results indicated that their content and distribution in different parts and cultivation years exhibit great variations. Gentiopicroside was identified as the most abundant compound among iridoid glycosides and its highest level was observed in the root of 2-year-old plant. With respect to qualitative variation of metabolic profile, the 1800–800 cm−1 band of FTIR spectra successfully discriminated different parts and cultivation years with the aid of PLS-DA. In addition, combined with PLSR, the feasibility of FTIR spectroscopy for determination of gentiopicroside was investigated by selecting characteristic wavelengths (1800–800 cm−1), which presented a good performance with a residual predictive deviation (RPD) of 3.646. Our results suggested that HPLC and FTIR techniques can complement each other and could be simultaneously applied for comparing and analyzing different parts and cultivation years of G. rigescens.
The Immunosignature of Mother/Fetus Couples in Gestational Diabetes Mellitus: Role of HLA-G 14 bp ins/del and PAPP-A A/C Polymorphisms in the Uterine Inflammatory Milieu
Authors: Martinetti Miryam , Beneventi Fausta , Capittini Cristina , Locatelli Elena , Simonetta Margherita , Cavagnoli Chiara , De Maggio Irene , De Silvestri Annalisa , Pasi Annamaria , Spinillo Arsenio
Published: June 2017

We enrolled 151 healthy mother/newborn couples and 26 with gestational diabetes mellitus (GDM). HLA-G and PAPP-A plasma levels were measured by ELISA at first and second trimesters, at delivery, and in cord blood. HLA-G 14 bp ins/del and PAPP-A A/C polymorphisms were genotyped. HLA-G del/del and PAPP-A C/C genotypes were more frequent among GDM mothers than controls. We observed a genetic epistasis between the two polymorphisms: the HLA-G del/del and PAPP-A C/C combination was carried by 8% of GDM mothers and 1.3% of controls (OR = 9.5, 95% CI = 0.8–109, p=0.07). GDM mothers showed increased sHLA-G levels compared to controls (p=0.004), and those carrying the HLA-G del/del genotype produced more sHLA-G at the second trimester and at delivery (p=0.014). A genetic pressure by fetal genotype on maternal sHLA-G production was observed in GDM mothers with heterozygous HLA-G del/ins newborns (p=0.02). Babies born to GDM mothers showed higher sHLA-G concentrations compared to those born to healthy mothers, and those carrying HLA-G del/del showed the highest sHLA-G levels (p=0.013). PAPP-A amounts significantly increased along pregnancy (p<0.001), but the median levels at the first and second trimesters were significantly lower in GDM (p=0.03). Our findings first suggest an involvement of HLA-G and PAPP-A gene-protein interaction in GDM and highlight a possible contribution of the fetus in balancing maternal inflammation.
Kinetics of Tyrosinase Inhibitory Activity Using Vitis vinifera Leaf Extracts
Authors: Lin Yung-Sheng , Chen Hui-Ju , Huang Jung-Ping , Lee Pei-Chi , Tsai Ching-Ru , Hsu Tzu-Fang , Huang Wen-Ying
Published: June 2017

Natural medical plant is considered as a good source of tyrosinase inhibitors. Red vine leaf extract (RVLE) can be applied to a wide variety of medical disciplines, such as treatments for chronic venous insufficiency over many decades. This study investigated the tyrosinase inhibitory activity of RVLE containing gallic acid, chlorogenic acid, epicatechin, rutin, and resveratrol which are effective for skin hyperpigmentation. The five components contents are 1.03, 0.2, 18.55, 6.45, and 0.48 mg/g for gallic acid, chlorogenic acid, epicatechin, rutin, and resveratrol. The kinetic study showed the tyrosinase inhibitory of RVLE via a competitive reaction mechanism. RVLE solution has an IC50 (the half inhibitory concentration) value of 3.84 mg/mL for tyrosinase inhibition, that is, an effective tyrosinase inhibitory activity, and can be used as a whitening agent for cosmetic formulations in the future.
Characterization of Soft Contact Lens Fitting Using Ultra-Long Scan Depth Optical Coherence Tomography
Authors: Cui Lele , Li Ming , Shen Meixiao , Lu Fan , Wang Jianhua
Published: June 2017

Objectives. To evaluate the centration and movement of soft contact lenses and to verify the repeatability of two repeated measurements of the lens centration and movement using ultra-long scan depth optical coherence tomography (UL-OCT). Methods. A 1-day Acuvue® Define™ lens was tested on both eyes of 10 subjects (5 males and 5 females; mean age, 31.6 years). The centration and blink-induced movement of the contact lens were measured using UL-OCT at 5 min and 30 min after insertion. The measurements were repeated once at each checkpoint. Results. Good repeatability was found in the lens centration and movement between the two repeated measurements at either checkpoint. The values of the lens movement were 0.457 ± 0.248 mm and 0.402 ± 0.229 mm at 5 min and decreased to 0.197 ± 0.065 mm and 0.211 ± 0.110 mm at 30 min after insertion for the right and left eyes, respectively (P<0.05). Conclusions. The custom-built UL-OCT presented good repeatability of centration and movement in Define lenses at 5 min and 30 min after insertion. Most of the lenses were centered temporal and inferior to the cornea during the first 30 min wearing period. Compared with 5 min after insertion, the lens was centered better and exhibited less movement at 30 min.
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.
Fluid Shear Stress and Fibroblast Growth Factor-2 Increase Endothelial Cell-Associated Vitronectin
Authors: Mathew Justin G. , Basehore Sarah , Clyne Alisa Morss
Published: June 2017

Vitronectin is a matricellular protein that plays an important role in both coagulation and angiogenesis through its effects on cell adhesion and the plasminogen system. Vitronectin is known to bind to endothelial cells upon integrin activation. However, the effect of integrin activation by shear stress and growth factors on cell-associated vitronectin and plasminogen system activity has not yet been studied. We therefore exposed human umbilical vein endothelial cells to steady laminar flow, oscillating disturbed flow, or fibroblast growth factor-2 (FGF-2) for 24 hours. We then measured cell-associated vitronectin by Western blot and plasminogen system activity using a Chromozym assay. Steady laminar flow, oscillating disturbed flow, and FGF-2 all increased cell-associated vitronectin, although the vitronectin molecular weight varied among the different conditions. FGF-2 also increased cell-associated vitronectin in microvascular endothelial cells and vascular smooth muscle cells. The increase in cell-associated vitronectin increased plasminogen system activity. Confocal microscopy showed that vitronectin was primarily located in the basal and intracellular regions.αvβ5integrin inhibition via genistein, an anti-αvβ5antibody, orβ5siRNA knockdown abrogated the FGF-2-induced increase in cell-associated vitronectin and increased plasminogen system activity. These data show that shear stress and growth factors increase cell-associated vitronectin through integrin activation, which may affect coagulation and angiogenesis.
Antipodal Vivaldi Antenna to Detect UHF Signals That Leaked Out of the Joint of a Transformer
Authors: Zhang Jian , Zhang Xiaoxing , Xiao Song
Published: June 2017

In recent years, extensive research has been conducted on the ultrahigh-frequency (UHF) method. Considering that acquiring a partial discharge UHF signal is the first step in a series of tasks, such as fault diagnosis and defect location, the UHF sensor plays an important role in the UHF method. An antipodal Vivaldi antenna installed at a transformer’s joint is designed in this study according to the structural features of 750 kV transformers in China. Several effective structures, such as linear gradient microstrip and slot edge, are employed to improve the return loss and radiation characteristics. A metal box is designed after analyzing the influence of the metal around the antenna. The metal box can effectively shield against electromagnetic interference and does not deteriorate the performance of the antenna significantly. Experimental data show that this antenna is much more sensitive than the rectangular plane spiral antenna. The proposed antipodal Vivaldi antenna is suitable for detecting partial discharge in large transformers.
Readability Assessment of Online Patient Education Material on Congestive Heart Failure
Authors: Kher Akhil , Johnson Sandra , Griffith Robert
Published: June 2017

Background. Online health information is being used more ubiquitously by the general population. However, this information typically favors only a small percentage of readers, which can result in suboptimal medical outcomes for patients. Objective. The readability of online patient education materials regarding the topic of congestive heart failure was assessed through six readability assessment tools. Methods. The search phrase “congestive heart failure” was employed into the search engine Google. Out of the first 100 websites, only 70 were included attending to compliance with selection and exclusion criteria. These were then assessed through six readability assessment tools. Results. Only 5 out of 70 websites were within the limits of the recommended sixth-grade readability level. The mean readability scores were as follows: the Flesch-Kincaid Grade Level (9.79), Gunning-Fog Score (11.95), Coleman-Liau Index (15.17), Simple Measure of Gobbledygook (SMOG) index (11.39), and the Flesch Reading Ease (48.87). Conclusion. Most of the analyzed websites were found to be above the sixth-grade readability level recommendations. Efforts need to be made to better tailor online patient education materials to the general population.
Mutational Signatures in Breast Cancer: The Problem at the DNA Level
Authors: Nik-Zainal Serena , Morganella Sandro
Published: June 2017

A 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

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

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.
Videolaryngoscopy during Conscious Sedation in Patients Not Suitable for Phonosurgery by Microlaryngoscopy: A Pilot Study
Authors: Saita Vincenzo , Allegra Eugenia , Marino Nicolò , Trapasso Serena , Monea Maria Concetta
Published: June 2017

Background: Microlaryngoscopy is the preferred and most widely used technique in phonosurgery for the treatment of benign and early malignant glottic lesions. However, the procedure may be technically difficult or impossible due to alterations of the cervical spine that may not allow hyperextension of the head or may present general anesthesia contraindications. The aim of this study is to evaluate the efficacy and safety of our surgical approach for lesions of the vocal folds in patients who are not suitable for phonosurgery by microlaryngoscopy. This approach applies videolaryngoscopy during conscious sedation, which combines local anesthesia with moderate analgosedation by using midazolam and fentanyl with premedication. Methods: A total of 235 patients affected by benign diseases or suspicious cancerous lesions of the vocal folds were retrospectively evaluated. Results: The method has shown a success rate of 95.5, 89, 52.3, and 86.7% in cases of polyps of the vocal folds, Reinke's edema, cysts of the vocal folds, and suspicious lesions of the larynx, respectively. Only 3 patients (1.27%) have been reported to experience adverse events. Conclusion: The results suggest that the method is an effective and safe procedure without relevant local and/or general complications.