bluuebunny/crossref_metadata_2025 huggingface dataset:
Engineering Cardiovascular Implant Surfaces to Create a Vascular Endothelial Growth Microenvironment
Authors: Li Jingan , Zhang Kun , Huang Nan
Published: September 2017

Cardiovascular disease (CVD) is generally accepted as the leading cause of morbidity and mortality worldwide, and an increasing number of patients suffer from atherosclerosis and thrombosis annually. To treat these disorders and prolong the sufferers’ life, several cardiovascular implants have been developed and applied clinically. Nevertheless, thrombosis and hyperplasia at the site of cardiovascular implants are recognized as long‐term problems in the practice of interventional cardiology. Here, we start this review from the clinical requirement of the implants, such as anti‐hyperplasia, anti‐thrombosis, and pro‐endothelialization, wherein particularly focus on the natural factors which influence functional endothelialization in situ, including the healthy smooth muscle cells (SMCs) environment, blood flow shear stress (BFSS), and the extracellular matrix (ECM) microenvironment. Then, the currently available strategies on surface modification of cardiovascular biomaterials to create vascular endothelial growth microenvironment are introduced as the main topic, e.g., BFSS effect simulation by surface micro‐patterning, ECM rational construction and SMCs phenotype maintain. Finally, the prospects for extending use of the in situ construction of endothelial cells growth microenvironment are discussed and summarized in designing the next generation of vascular implants.
Tuning the Size of Poly(lactic‐co‐glycolic Acid) (PLGA) Nanoparticles Fabricated by Nanoprecipitation
Authors: Huang Wei , Zhang Chenming
Published: September 2017

Polymeric nanoparticles (PNPs) are promising drug carriers in cancer treatment. Size of the particles has a significant impact on drug loading, in vivo distribution, extravasation, intratumor diffusion and cell uptake, and thus is critical for the successful development of a drug delivery regime. However, methods for manufacturing PNPs of defined size are yet to be established. The goal of this study is to establish a method that can be used to fabricate PNPs with controlled size. The factors that could impact the size of PNPs fabricated by nano‐precipitation are systematically investigated. The factors studied include polymer concentration, organic solvent, temperature, aqueous phase ionic strength, organic phase injection rate, aqueous phase agitation rate, gauge of the needles, and final polymer concentration. Polymer concentration, the choice of organic solvent, temperature, and the ionic strength of the aqueous phase are shown to have a significant impact on the size of PNPs, and the effect of these factors can be attributed to a single parameter, the diffusion coefficient of the solvent in water, Dpw. It is possible that by tightly control these four parameters, nanoparticles with highly predictable and desirable size with narrow size distribution can be fabricated.
Burkholderia cepacia lipase: A versatile catalyst in synthesis reactions
Authors: Sánchez Daniel A. , Tonetto Gabriela M. , Ferreira María L.
Published: September 2017

The lipase from Burkholderia cepacia, formerly known as Pseudomonas cepacia lipase, is a commercial enzyme in both soluble and immobilized forms widely recognized for its thermal resistance and tolerance to a large number of solvents and short‐chain alcohols. The main applications of this lipase are in transesterification reactions and in the synthesis of drugs (because of the properties mentioned above). This review intends to show the features of this enzyme and some of the most relevant aspects of its use in different synthesis reactions. Also, different immobilization techniques together with the effect of various compounds on lipase activity are presented. This lipase shows important advantages over other lipases, especially in reaction media including solvents or reactions involving short‐chain alcohols.
Advancements in the design and scalable production of viral gene transfer vectors
Authors: Sharon David , Kamen Amine
Published: September 2017

The last 10 years have seen a rapid expansion in the use of viral gene transfer vectors, with approved therapies and late stage clinical trials underway for the treatment of genetic disorders, and multiple forms of cancer, as well as prevention of infectious diseases through vaccination. With this increased interest and widespread adoption of viral vectors by clinicians and biopharmaceutical industries, there is an imperative to engineer safer and more efficacious vectors, and develop robust, scalable and cost‐effective production platforms for industrialization. This review will focus on major innovations in viral vector design and production systems for three of the most widely used viral vectors: Adenovirus, Adeno‐Associated Virus, and Lentivirus.
Safety and efficacy of the next generation Resolute Onyx zotarolimus‐eluting stent: Primary outcome of the RESOLUTE ONYX core trial
Authors: Price Matthew J. , Shlofmitz Richard A. , Spriggs Douglas J. , Haldis Thomas A. , Myers Paul , Popma Almonacid Alexandra , Maehara Akiko , Dauler Michelle , Peng Yun , Mehran Roxana
Published: September 2017

Objectives

To assess the safety and efficacy of the novel Resolute (R‐) Onyx drug‐eluting stent (DES).

Background

The R‐Onyx DES consists of a composite wire with an outer shell of cobalt chromium alloy and a platinum‐iridium inner core to enhance radiopacity, with thinner, swaged struts and modified stent geometry compared with the predicate Resolute DES, resulting in a slightly lower total drug load in most sizes.

Methods

This was a prospective, single‐arm non‐inferiority trial compared with a historical control. Patients with stable angina/ischemia and up to 2 de novo target lesions ≤35 mm long with reference vessel diameter (RVD) of 2.25–4.2 mm were enrolled. The primary endpoint was late lumen loss at 8‐month follow‐up. Propensity‐score adjusted outcomes from the single‐arm RESOLUTE‐US trial served as the control.

Results

Seventy‐five patients (85 lesions) were enrolled. Mean patient age was 66 ± 9 years, 73% were male, and 32% had diabetes. Mean lesion length was 14.28 ± 6.68 mm, mean RVD was 2.57 ± 0.48 mm, and 86% of lesions were class B2/C. In‐stent late lumen loss at 8 months was 0.24 ± 0.39 mm with R‐Onyx DES compared with 0.36 ± 0.52 mm with Resolute DES (P < 0.001 for noninferiority, P = 0.029 for superiority). At 8 months, clinically driven target lesion revascularization occurred in 3 patients (4.0%) and target lesion failure occurred in 5 patients (6.7%).

Conclusions

In‐stent late lumen loss is non‐inferior, and appears to be superior, with the thin‐strut novel composite wire R‐Onyx DES compared with Resolute DES. Continued evolution of stent design can improve angiographic outcomes in complex lesions, even in the current era of next‐generation DES.
Isolated myeloid sarcoma as the first manifestation of acute myeloid leukemia: a case study
Authors: Mitkowski Dorothy , Gil Lidia
Published: September 2017

Key Clinical Message

This case report brings awareness to the diverse extramedullary manifestations of isolated myeloid sarcoma, as well as the importance and difficulties that are associated with establishing a rapid diagnosis and initiating treatment.
Influence of Hydrodynamic Disintegration on the Release of Organic and Nutrient Compounds From Activated Sludge
Authors: Walczak Justyna , Zubrowska‐Sudol Monika , Piechna Paula
Published: September 2017

The aim of the research is to assess the release of organic compounds and nutrients to liquid phase as a result of hydrodynamic disintegration (HD) of sludge. Six batch disintegration tests are conducted. The scope is a complex analysis of the release of organic compounds (soluble chemical oxygen demand [SCOD], volatile fatty acids [VFA]) and nutrients (soluble total nitrogen [STN], NO2−‐N, NO3−‐N, NH4+‐N, soluble total phosphorus [STP], PO43–‐P) depending on the energy density (ϵL) used during the HD process (70–350 kJ L−1). It is shown that an increase in ϵL is correlated with an increase in the disintegration degree (DD). This results in an increase in both the SCOD (including VFA) and in the soluble nutrient concentration (STN and STP). The value of ϵL, at which HD is conducted, also has an influence on the percentage share of VFA in soluble organic compounds released from activated sludge flocs and on the relationship between the SCOD/STN and SCOD/STP ratio. It is also shown that ϵL and the total solids concentration of disintegrated sludge have an influence on the costs of organic compounds acquired by the HD method. Low costs are obtained for ϵL = 350 kJ L−1 (0.7–2.2 € kg−1 SCOD and 12.8–23.64.0 € kg−1 VFA), and for relatively high total solids (TS) concentrations (TS > 4%) (1.5–1.9 € kg−1 SCOD for ϵL = 70 kJ kg−1 and 0.7–0.8 € kg−1 SCOD for ϵL = 350 kJ L−1).
Impact of CYP2D6 Functional Allelic Variations on Phenoconversion and Drug–Drug Interactions
Authors: Storelli Flavia , Matthey Alain , Lenglet Sébastien , Thomas Aurélien , Desmeules Jules , Daali Youssef
Published: September 2017

We investigated whether CYP2D6 extensive metabolizers carrying a nonfunctional allele are at higher risk of phenoconversion to poor metabolizers in the presence of CYP2D6 inhibitors. Seventeen homozygous carriers of two fully‐functional alleles and 17 heterozygous carriers of one fully‐functional and one nonfunctional allele participated in this trial. Dextromethorphan 5 mg and tramadol 10 mg were given at each of the three study sessions. CYP2D6 was inhibited by duloxetine 60 mg (session 2) and paroxetine 20 mg (session 3). A higher rate of phenoconversion to intermediate metabolizers with duloxetine (71% vs. 25%, P = 0.009) and to poor metabolizers with paroxetine (94% vs. 56%, P = 0.011) was observed in heterozygous than homozygous extensive metabolizers. The magnitude of drug–drug interaction between dextromethorphan and paroxetine was higher in homozygous than in heterozygous subjects (14.6 vs. 8.5, P < 0.028). Our study suggests that genetic extensive metabolizers may not represent a homogenous population and that available genetic data should be considered when addressing drug–drug interactions in clinical practice.
Charge‐Transfer Character in a Covalent Diketopyrrolopyrrole Dimer: Implications for Singlet Fission
Authors: Mauck Catherine M. , Bae Youn Jue , Chen Michelle , Powers‐Riggs Natalia , Wu Yi‐Lin , Wasielewski Michael R.
Published: September 2017

Diketopyrrolopyrrole (DPP) is a strongly absorbing, photostable chromophore that can undergo singlet fission (SF), a photophysical process that promises to significantly enhance solar‐cell performance. In the solid state, DPP packs in a herringbone arrangement that maximizes intermolecular donor–acceptor interactions, suggesting that charge‐transfer (CT) states play a role in DPP SF. In order to characterize intermolecular DPP CT states in molecular assemblies, we have synthesized a covalent DPP dimer bridged by a xanthene linker, which places two thiophene‐substituted DPPs (TDPPs) in a cofacial arrangement that mimics chromophore π–π stacking in the thin film. After photoexcitation in polar solvents, symmetry‐breaking charge separation forms the fully charge separated TDPP+.–TDPP−. ion‐pair state. In nonpolar solvents, charge separation is incomplete leading to the TDPPδ+–TDPPδ− CT state, which is in pseudoequilibrium with the relaxed S1S0 state observed by transient absorption and emission spectroscopy. This study highlights the importance of intramolecular coupling as well as the importance of entropy to promoting SF in chromophore dimers for which SF is endo‐ or isoergic.
Military‐related trauma is associated with eating disorder symptoms in male veterans
Authors: Arditte Hall Kimberly A. , Bartlett Brooke A. , Iverson Katherine M. , Mitchell Karen S.
Published: September 2017

Objective

Eating disorders are understudied among male veterans, who may be at increased risk due to the high rates of trauma exposure and experiences of multiple traumatization in this population. This study sought to examine the associations between specific types of trauma (i.e., childhood physical abuse, adult physical assault, childhood sexual abuse, adult sexual assault, and military‐related trauma) and eating disorder symptoms in a large, nationally‐representative sample of trauma‐exposed male veterans.

Method

Survey data were collected from N = 642 male veterans. Traumatic experiences in childhood and adulthood were assessed using the Trauma History Screen and the National Stressful Events Survey. Eating disorder symptoms were assessed with the Eating Disorder Diagnostic Scale. Analyses also controlled for age and body mass index.

Results

Multiple traumatization was associated with increased eating disorder symptoms. However, military‐related trauma was the only trauma type that was uniquely associated with eating disorder symptoms when controlling for other trauma types. Examination of different types of military‐related trauma indicated that this association was not driven by exposure to combat.

Discussion

Noncombat, military‐related trauma was associated with eating disorder symptom severity in male veterans. Results highlight the need for better assessment of eating disorder symptoms in this population.
Sex and weaponry: The distribution of toxin‐storage glands on the bodies of male and female cane toads (Rhinella marina)
Authors: Chen Wei , Hudson Cameron M. , DeVore Jayna L. , Shine Richard
Published: September 2017

The parotoid macroglands of bufonid anurans store (and can expel) large volumes of toxic secretions and have attracted detailed research. However, toxins also are stored in smaller glands that are distributed on the limbs and dorsal surface of the body. Female and male cane toads (Rhinella marina) differ in the location of toxin‐storage glands and the extent of glandular structures. Female toads store a larger proportion of their toxins in the parotoids than males as well as (to a lesser extent) in smaller glands on the forelimbs. Males have smaller and more elongate parotoids than females, but glands cover more of the skin surface on their limbs (especially hindlimbs) and dorsal surface. The delay to toxin exudation in response to electrostimulation varied among glands in various parts of the body, and did so differently in males than in females. The spatial distribution of toxin glands differs between the sexes even in toads that have been raised under standardized conditions in captivity; hence, the sexual dimorphism is due to heritable factors rather than developmentally plastic responses to ecological (e.g., habitat, predation risk) differences between the sexes. The selective advantages of this sexual dimorphism remain unclear. A priori, we might expect to see toxin widely dispersed across any part of the body likely to be contacted by a predator; and a wide distribution also would be expected if the gland secretions have other (e.g., male–male rivalry) functions. Why, then, is toxin concentrated in the parotoids, especially in female toads? That concentration may enhance the effectiveness of frontal displays to deter predation and also may facilitate the transfer of stored toxins to eggs.
Phylogeographic and phylogenetic analysis for Tripterygium species delimitation
Authors: Ma Baowei , Hu Tianyuan , Li Pei , Yuan Qingjun , Lin Zhaoshou , Tu Yuhe , Li Jia , Zhang Xianan , Wu Xiaoyi , Wang Xiujuan , Huang Luqi , Gao Wei
Published: September 2017

Tripterygium wilfordii (Celastraceae) is a traditional Chinese medicine; and the dried root and rhizome constitute the main officinal parts. Tripterygium wilfordii has been identified as a potential candidate for the treatment of systemic lupus erythematosus, rheumatoid arthritis, nephritis, asthma, leprosy, and cancer. The phylogenetic relationships within the Tripterygium genus are ambiguous; thus, our aim is to clarify the relationships within this genus using phylogeographic and phylogenetic analyses. Here, we first sequenced three plastid DNA regions (i.e., psbA‐trnH, rpl32‐trnL, and trnL‐trnF) and found that Tripterygium hypoglaucum and T. wilfordii were clustered together based on the strength of the topology in the phylogenetic analysis: T. hypoglaucum is polyphyletic, and T. wilfordii is paraphyletic. A spatial analysis of molecular variance showed that the best group value is 4, and the groups were almost consistent with the topology of in the phylogenetic analysis. The Mantel analyses of Tripterygium using IBD web showed statistically significant relationships between genetic and geographical distance distributions (r = .3479, p < .0001). The molecular dating using Fossil calibration indicated that the divergence in Tripterygium was approximately 8.13 Ma. Furthermore, we also analyzed four DNA regions (i.e., ITS2, psbA‐trnH, matK, and rbcL) that were obtained from the NCBI nucleotide database; these results showed that T. wilfordii and T. hypoglaucum clustered together, while Tripterygium regelii represented a separate cluster. Tripterygium hypoglaucum and T. wilfordii were never distinct lineages, and the species circumscriptions are artificial. We propose that T. wilfordii and T. hypoglaucum are conspecific, while T. regelii likely constitutes a separate species.
Predicting individual plant performance in grasslands
Authors: Herz Katharina , Dietz Sophie , Haider Sylvia , Jandt Ute , Scheel Dierk , Bruelheide Helge
Published: September 2017

Plant functional traits are widely used to predict community productivity. However, they are rarely used to predict individual plant performance in grasslands. To assess the relative importance of traits compared to environment, we planted seedlings of 20 common grassland species as phytometers into existing grassland communities varying in land‐use intensity. After 1 year, we dug out the plants and assessed root, leaf, and aboveground biomass, to measure plant performance. Furthermore, we determined the functional traits of the phytometers and of all plants growing in their local neighborhood. Neighborhood impacts were analyzed by calculating community‐weighted means (CWM) and functional diversity (FD) of every measured trait. We used model selection to identify the most important predictors of individual plant performance, which included phytometer traits, environmental conditions (climate, soil conditions, and land‐use intensity), as well as CWM and FD of the local neighborhood. Using variance partitioning, we found that most variation in individual plant performance was explained by the traits of the individual phytometer plant, ranging between 19.30% and 44.73% for leaf and aboveground dry mass, respectively. Similarly, in a linear mixed effects model across all species, performance was best predicted by phytometer traits. Among all environmental variables, only including land‐use intensity improved model quality. The models were also improved by functional characteristics of the local neighborhood, such as CWM of leaf dry matter content, root calcium concentration, and root mass per volume as well as FD of leaf potassium and root magnesium concentration and shoot dry matter content. However, their relative effect sizes were much lower than those of the phytometer traits. Our study clearly showed that under realistic field conditions, the performance of an individual plant can be predicted satisfyingly by its functional traits, presumably because traits also capture most of environmental and neighborhood conditions.
Nonalcoholic fatty liver disease incidence and impact on metabolic burden and death: A 20 year‐community study
Authors: Allen Alina M. , Therneau Terry M. , Larson Joseph J. , Coward Alexandra , Somers Virend K. , Kamath Patrick S.
Published: September 2017

Recent population‐based data on nonalcoholic fatty liver disease (NAFLD) epidemiology in general, and incidence in particular, are lacking. We examined trends in NAFLD incidence in a U.S. community and the impact of NAFLD on incident metabolic comorbidities (MCs), cardiovascular (CV) events, and mortality. A community cohort of all adults diagnosed with NAFLD in Olmsted County, Minnesota, between 1997 and 2014 was constructed using the Rochester Epidemiology Project database. The yearly incidence rate were calculated. The impact of NAFLD on incident MCs, CV events, and mortality was studied using a multistate model, with a 4:1 age‐ and sex‐matched general population as a reference. We identified 3,869 NAFLD subjects (median age, 53; 52% women) and 15,209 controls; median follow‐up was 7 (1‐20) years. NAFLD incidence increased 5‐fold, from 62 to 329 in 100,000 person‐years. The increase was highest (7‐fold) in young adults, aged 18‐39 years. The 10‐year mortality was higher in NAFLD subjects (10.2%) than controls (7.6%; P < 0.0001). NAFLD was an independent risk factor for incident MCs and death. Mortality risk decreased as the number of incident MCs increased: relative risk (RR) = 2.16 (95% confidence [CI], 1.41‐3.31), 1.99 (95% CI, 1.48‐2.66), 1.75 (95% CI, 1.42‐2.14), and 1.08 (95% CI, 0.89‐1.30) when 0, 1, 2, or 3 MCs were present, respectively. The NAFLD impact on CV events was significant only in subjects without MCs (RR = 1.96; 95% CI = 1.35‐2.86). NAFLD reduced life expectancy by 4 years, with more time spent in high metabolic burden. Conclusion: Incidence of NAFLD diagnosis in the community has increased 5‐fold, particularly in young adults. NAFLD is a consequence, but also a precursor of MC. Incident MC attenuates the impact of NAFLD on death and annuls its impact on CV disease. (Hepatology 2018;67:1726‐1736).
Status of implementation and organization of cancer screening in The European Union Member States—Summary results from the second European screening report
Authors: Basu Partha , Ponti Antonio , Anttila Ahti , Ronco Guglielmo , Senore Carlo , Vale Diama Bhadra , Segnan Nereo , Tomatis Mariano , Soerjomataram Isabelle , Primic Žakelj Maja , Dillner Joakim , Elfström Klara Miriam , Lönnberg Stefan , Sankaranarayanan Rengaswamy
Published: September 2017

The second report on the implementation status of cancer screening in European Union (EU) was published in 2017. The report described the implementation status, protocols and organization (updated till 2016) and invitation coverage (for index year 2013) of breast, cervical and colorectal cancer screening in the EU. Experts in screening programme monitoring (N = 80) from the EU Member States having access to requisite information in their respective countries provided data on breast, cervical and colorectal cancer screening through online questionnaires. Data was collected for screening performed in the framework of publicly mandated programmes only. Filled in questionnaires were received from 26 Member States for all three sites and from one Member State for breast cancer only. Substantial improvement in screening implementation using population‐based approach was documented. Among the age‐eligible women, 94.7% were residents of Member States implementing or planning population‐based breast cancer screening in 2016, compared to 91.6% in 2007. The corresponding figures for cervical cancer screening were 72.3 and 51.3% in 2016 and 2007, respectively. Most significant improvement was documented for colorectal cancer screening with roll‐out ongoing or completed in 17 Member States in 2016, compared to only five in 2007. So the access to population‐based screening increased to 72.4% of the age‐eligible populations in 2016 as opposed to only 42.6% in 2007. The invitation coverage was highly variable, ranging from 0.2–111% for breast cancer, 7.6–105% for cervical cancer and 1.8–127% for colorectal cancer in the target populations. In spite of the considerable progress, much work remains to be done to achieve optimal effectiveness. Continued monitoring, regular feedbacks and periodic reporting are needed to ensure the desired impacts of the programmes.
Emerging roles of syndecan 2 in epithelial and mesenchymal cancer progression
Authors: Mytilinaiou Maria , Nikitovic Dragana , Berdiaki Aikaterini , Kostouras Antonis , Papoutsidakis Antonis , Tsatsakis Aristidis M. , Tzanakakis George N.
Published: September 2017

Syndecan 2 (SDC2) belongs to a four‐member family of evolutionary conserved small type I transmembrane proteoglycans consisting of a protein core to which glycosaminoglycan chains are covalently attached. SDC2 is a cell surface heparan sulfate proteoglycan, which is increasingly drawing attention for its distinct characteristics and its participation in numerous cell functions, including those related to carcinogenesis. Increasing evidence suggests that the role of SDC2 in cancer pathogenesis is dependent on cancer tissue origin rendering its use as a biomarker/therapeutic target feasible. This mini review discusses the mechanisms, through which SDC2, in a distinct manner, modulates complex signalling networks to affect cancer progression. © 2017 IUBMB Life, 69(11):824–833, 2017
Multimodal pore formation in calcium phosphate cements
Authors: Lodoso‐Torrecilla Irene , van Gestel Nicole A. P. , Diaz‐Gomez Luis , Grosfeld Eline‐Claire , Laperre Kjell , Wolke Joop G. C. , Smith Brandon T. , Arts Jacobus J. , Mikos Antonios G. , Jansen John A. , Hofmann Sandra , van den Beucken Jeroen J. J. P.
Published: September 2017

Calcium phosphate cements (CPCs) are commonly used as bone substitute materials. However, their slow degradation rate and lack of macroporosity hinders new bone formation. Poly(dl‐lactic‐co‐glycolic acid) (PLGA) incorporation is of great interest as, upon degradation, produces acidic by‐products that enhance CPC degradation. Yet, new bone formation is delayed until PLGA degradation occurs a few weeks after implantation. Therefore, the aim of this study was to accelerate the early stage pore formation within CPCs in vitro. With that purpose, we incorporated the water‐soluble porogen sucrose at different weight percentages (10 or 20 wt %) to CPC and CPC/PLGA composites. The results revealed that incorporation of sucrose porogens increased mass loss within the first week of in vitro degradation in groups containing sucrose compared to control groups. After week 1, a further mass loss was observed related to PLGA and CPC degradation. Macroporosity analysis confirmed that macroporosity formation is influenced by the dissolution of sucrose at an early stage and by the degradation of PLGA and CPC at a later stage. We concluded that the combination of sucrose and PLGA porogens in CPC is a promising approach to promote early stage bone tissue ingrowth and complete replacement of CPC through multimodal pore formation. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 500–509, 2018.
ASFA Category IV becomes Category I: Idiopathic thrombotic thrombocytopenic purpura in a patient with presumed gemcitabine‐induced thrombotic microangiopathy
Authors: Bittar Peter G. , Nickolich Myles S. , Onwuemene Oluwatoyosi A.
Published: September 2017

In the implementation of American Society for Apheresis national guidelines, the decision for therapeutic plasma exchange may be confounded by a clinical presentation that fits both a Category I and IV designation. We report the case of a 45‐year‐old female who presented with concern for a Category IV disorder, gemcitabine‐induced thrombotic microangiopathy, and was ultimately diagnosed with a Category I disorder, idiopathic thrombotic thrombocytopenic purpura. This case highlights the importance of ruling out idiopathic TTP by a thorough evaluation for ADAMTS13 activity and inhibitor, even when an alternate thrombotic microangiopathy diagnosis may be likely.
Effects of placebo‐controlled insulin‐sensitizing drugs on hormonal parameters in polycystic ovary syndrome patients: A network meta‐analysis
Authors: Huang Rong , Zhao Peng‐Fei , Xu Jian‐Hua , Liu Dong‐Dong , Luo Fu‐Dong , Dai Yong‐Hui
Published: September 2017

This network meta‐analysis was conducted to compare effects of different placebo‐controlled insulin‐sensitizing drugs, including metformin, pioglitazone, rosiglitazone, and troglitazone on hormonal parameters in polycystic ovary syndrome (PCOS) patients. We searched PubMed, EMBASE, and Cochrane Library databases from their inception to July 2017. Randomized controlled trials (RCTs) met our inclusion criteria were included. We combined direct and indirect evidences to evaluate weighted mean difference (WMD) value and draw surface under the cumulative ranking curve (SUCRA). Totally 28 eligible RCTs were enrolled. The network meta‐analysis results indicated that: Compared with placebo, patients treated with pioglitazone had relatively higher sex‐hormone‐binding globulin (SHBG) (nmol/L) level (WMD = 6.65, 95%CI = 0.57‐12.98), patients treated with metformin had comparatively lower total testosterone (TT) (ng/mL) level (WMD = −0.20, 95%CI = −0.39 to −0.02); Compared with rosiglitazone, patients treated with metformin had relatively higher estradiol (E2) (pg/mL) level (WMD = 47.91, 95%CI = 11.44‐85.55). However, there were no statistical significance among the placebo‐controlled insulin‐sensitizing drugs in follicle stimulating hormone (FSH) (IU/L), luteinizing hormone (LH) (IU/L), dehydroepiandrostrone‐sulphate (DHEAS) (µg/dL), free testosterone (FT) (pg/mL) and androstenedione (ng/mL). The results of cluster analysis showed that rosiglitazone may be the best drug for PCOS patients regarding to DHEAS, TT, FSH, and LH, metformin may be the best drug for PCOS patients as for E2, FT, and androstenedione. Rosiglitazone had the best effect on PCOS patients in terms of DHEAS, TT, FSH, and LH, metformin had the best effect on PCOS patients for E2, FT, and androstenedione.
Collagen, agarose, alginate, and Matrigel hydrogels as cell substrates for culture of chondrocytes in vitro: A comparative study
Authors: Miao Zhikang , Lu Zhenhui , Wu Huayu , Liu Hui , Li Muyan , Lei Danqing , Zheng Li , Zhao Jinmin
Published: September 2017

Autologous chondrocyte implantation (ACI) has emerged as a new approach to cartilage repair through the use of harvested chondrocytes. But the expansion of the chondrocytes from the donor tissue in vitro is restricted by limited cell numbers and dedifferentiation of chondrocytes. In this study, we used four types of hydrogels including agarose, alginate, Matrigel, and collagen type I hydrogels to serve as cell substrates and investigated the effect on proliferation and phenotype maintenance of chondrocytes. As a substrate for monolayer culture, collagen facilitated cell expansion and effectively suppressed the dedifferentiation of chondrocytes, as evidenced by fluorescein diacetate/propidium iodide (FDA/PI), hematoxylin‐eosin staining (HE), Safranin O, immunofluorescenceassay, biochemistry analysis, and quantitative real‐time polymerase chain reaction (qRT‐PCR). Compared with that in agarose gels, alginate, and Matrigel, collagen accelerated cell proliferation and enhanced the expression of cartilage specific genes such as ACAN, SOX9, and COLII more markedly. Furthermore, significantly lower expression of COL I (an indicator of dedifferentiation) and COL X (the chondrocyte hypertrophy marker) was present in collagen group than in other groups. This indicated that collagen substrate can better support chondrocyte growth and maintain cell phenotype, due to that it might serve as a cartilage‐like ECM to provide adhesive site for chondrocytes. In summary, collagen hydrogel is a promising cell substrate for chondrocytes culture for ACI.
Inducing indel mutation in the SOX6 gene by zinc finger nuclease for gamma reactivation: An approach towards gene therapy of beta thalassemia
Authors: Modares Sadeghi Mehran , Shariati Laleh , Hejazi Zahra , Shahbazi Mansoureh , Tabatabaiefar Mohammad Amin , Khanahmad Hossein
Published: September 2017

β‐thalassemia is a common autosomal recessive disorder characterized by a deficiency in the synthesis of β‐chains. Evidences show that increased HbF levels improve the symptoms in patients with β‐thalassemia or sickle cell anemia. In this study, ZFN technology was applied to induce a mutation in the binding domain region of SOX6 to reactivate γ‐globin expression. The sequences coding for ZFP arrays were designed and sub cloned in TDH plus as a transfer vector. The ZFN expression was confirmed using Western blot analysis. In the next step, using the site‐directed mutagenesis strategy through the overlap PCR, a missense mutation (D64V) was induced in the catalytic domain of the integrase gene in the packaging plasmid and verified using DNA sequencing. Then, the integrase minus lentivirus containing ZFN cassette was packaged. Transduction of K562 cells with this virus was performed. Mutation detection assay was performed. The indel percentage of the cells transducted with lenti virus containing ZFN was 31%. After 5 days of erythroid differentiation with 15 μg/mL cisplatin, the levels of γ‐globin mRNA were sixfold in the cells treated with ZFN compared to untreated cells. In the meantime, the measurement of HbF expression levels was carried out using hemoglobin electrophoresis and showed the same results. Integrase minus lentivirus can provide a useful tool for efficient transient gene expression and helps avoid disadvantages of gene targeting using the native virus. The ZFN strategy applied here to induce indel on SOX6 gene in adult erythroid progenitors may provide a method to activate fetal hemoglobin expression in individuals with β‐thalassemia.
Retracted: In vivo and in vitro effects of microRNA‐124 on human gastric cancer by targeting JAG1 through the Notch signaling pathway
Authors: Xiao Hai‐Juan , Ji Qing , Yang Lin , Li Ren‐Ting , Zhang Cheng , Hou Jun‐Ming
Published: September 2017

In this study, we aim to determine the function of miR‐124 on gastric cancer (GC) cells and the underlying mechanism that involves jaddeg1 (JAG1) and the Notch signaling pathway. GC tissues and adjacent tissues from 100 patients suffering from GC were selected. GC SGC‐7901 and AGS cells were selected and grouped into control, mimic‐NC, miR‐124 mimic, inhibitor‐NC, miR‐124 inhibitor, and miR‐124 inhibitor + si‐JAG1 groups. RT‐qPCR and a Western blotting assay were conducted to detect the expression of miR‐124, JAG1, and Notch signaling pathway‐related proteins (NICD, HES1, and HES5). MTS, wound‐healing, transwell assay and flow cytometry were performed to detect cell proliferation, migration, invasion, cell cycle distribution, and apoptosis, respectively. Compared with adjacent tissues, a lower miR‐124 expression and higher JAG1 expression were found in GC tissues. JAG1 is a direct target gene of miR‐124. Compared with the control group, the expression of JAG1, NICD, HES1, and HES5, cell invasion, migration, and proliferation in the miR‐124 mimic group were decreased, while the apoptosis rate was increased and cells were arrested at the G0/G1 phase. Compared with the miR‐124 inhibitor group, the expression of JAG1, NICD, HES1, and HES5, cell invasion, migration, and proliferation in the miR‐124 inhibitor + si‐JAG1 group were decreased, while the apoptosis rate and cell ratio at the G0/G1 phase were increased. The demonstration that miR‐124 inhibits GC cell growth supports the concept that miR‐124 functions as a tumor suppressor by a mechanism that involves translational repression of the JAG1 and the inhibition of Notch signaling pathway.
Retracted: SHH gene silencing suppresses epithelial‐mesenchymal transition, proliferation, invasion, and migration of cervical cancer cells by repressing the hedgehog signaling pathway
Authors: Zhang Feng , Ren Chen‐Chen , Liu Ling , Chen Yan‐Nan , Yang Li , Zhang Xiao‐An , Wang Xiao‐Ming , Yu Feng‐Jing
Published: September 2017

The above article, published online on 27 October 2017 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor in Chief, Gary Stein and Wiley Periodicals, Inc. The retraction has been agreed due to determination by the authors that the data relating to infiltration and metastasis presented in this publication is incomplete and there is need for further study and analysis.

Reference

Zhang F, Ren C‐C, Liu L, et al. SHH gene silencing suppresses epithelial‐mesenchymal transition, proliferation, invasion, and migration of cervical cancer cells by repressing the hedgehog signaling pathway. J Cell Biochem. 2018;119:3829–3842. https://doi.org/10.1002/jcb.26414.
A component analysis of the free energies of folding of 35 proteins: A consensus view on the thermodynamics of folding at the molecular level
Authors: DasGupta Debarati , Mandalaparthy Varun , Jayaram Bhyravabhotla
Published: September 2017

What factors favor protein folding? This is a textbook question. Parsing the experimental free energies of folding/unfolding into diverse enthalpic and entropic components of solute and solvent favoring or disfavoring folding is not an easy task. In this study, we present a computational protocol for estimating the free energy contributors to protein folding semi‐quantitatively using ensembles of unfolded and native states generated via molecular dynamics simulations. We tested the methodology on 35 proteins with diverse structural motifs and sizes and found that the calculated free energies correlate well with experiment (correlation coefficient ∼ 0.85), enabling us to develop a consensus view of the energetics of folding. As a more sensitive test of the methodology, we also investigated the free energies of folding of an additional 33 single point mutants and obtained a correlation coefficient of 0.8. A notable observation is that the folding free energy components appear to carry signatures of the fold (SCOP classification) of the protein. © 2017 Wiley Periodicals, Inc.
Suppressing angiogenesis regulates the irradiation‐induced stimulation on osteoclastogenesis in vitro
Authors: Tong Ling , Zhu Guoying , Wang Jianping , Sun Ruilian , He Feilong , Zhai Jianglong
Published: September 2017

Ionizing radiation‐induced bone loss is a potential health concern in radiotherapy, occupational exposure, and astronauts. Although impaired bone vasculature and reduced proliferation of bone‐forming osteoblasts has been implicated in this process, it has not been clearly characterized that whether radiation affects the growth of bone‐resorbing osteoclasts. The molecular crosstalk between different cell populations in the skeletal system has not yet been elucidated in detail, especially between the increased bone resorption at early stage of post‐irradiation and bone marrow‐derived endothelial progenitor cells (BM‐EPCs). In order to further understand the mechanisms involved in radiation‐induced bone loss at the cellular level, we assessed the effects of irradiation on angiogenesis of BM‐EPCs and osteoclastogenesis of receptor activator for nuclear factor‐κB ligand (RANKL)‐stimulated RAW 264.7 cells and crosstalk between these cell populations. We herein found significantly dysfunction of BM‐EPCs in response to irradiation at a dose of 2 Gy, including inhibited proliferation, migration, tube‐forming abilities, and downregulated expression of pro‐angiogenesis vascular endothelial growth factors A (VEGF A). Meanwhile, we observed that irradiation promoted osteoclastogenesis of RANKL‐stimulated RAW 264.7 cells directly or indirectly. These results provide quantitative evidences of irradiation induced osteoclastogenesis at a cellular level, and strongly suggest the involvement of osteoclastogenesis, angiogenesis and crosstalk between bone marrow cells in the radiation‐induced bone loss. This study may provide new insights for the early diagnosis and intervention of bone loss post‐irradiation.
Process design of carbon dioxide and ethane separation using ionic liquid by extractive distillation
Authors: Zhu Zhaoyou , Hu Jiajing , Geng Xueli , Qin Bin , Ma Kang , Wang Yinglong , Gao Jun
Published: September 2017

BACKGROUND

Carbon dioxide and ethane easily form a binary azeotrope under liquefied conditions. An extractive distillation process for the separation of carbon dioxide and ethane using the ionic liquids [bmim][Tf2N], [emim][Tf2N] and [emim][EtSO4] as solvents was explored. The thermodynamic and physical property parameters of each ionic liquid and their thermo‐physical properties that correlated with the experimental data were used to create the ionic liquid components and conduct the process simulation.

RESULT

Based on the analysis of its physical properties and relative volatilities, [emim][Tf2N] is the best option as a solvent for extractive distillation separation compared with other ionic liquids. Based on the sensitivity analysis optimization procedure, the minimum total annual cost, carbon dioxide emissions and thermodynamic efficiency were calculated. Compared with traditional extraction distillation, the total annual cost and carbon dioxide emissions of the process using [emim][Tf2N] as a solvent decreased by 62% and 31%, respectively. The thermodynamic efficiency (η) of the electricity generated from hydropower increase by 0.7%.

CONCLUSION

The results show that an ionic liquid extractive distillation process using an ionic liquid as the entrainer performs better than a process using traditional organic solvents in terms of economics. Due to the non‐volatility of ionic liquids, a flash tank was used instead of a solvent recovery column to efficiently realize solvent recovery. © 2017 Society of Chemical Industry
Changes in pulmonary artery systolic pressure correlate with radiographic severity and peripheral oxygenation in adults with community‐acquired pneumonia
Authors: Sreter Katherina Bernadette , Budimir Ivan , Golub Andrija , Dorosulić Zdravko , Sabol Pušić Mateja , Boban Marko
Published: September 2017

Purpose

The aim of this prospective observational study was to evaluate the relationship between changes in pulmonary artery systolic pressure (ΔPASP) and both severity of community‐acquired pneumonia (CAP) and changes in peripheral blood oxygen partial pressure (PaO2).

Materials and Methods

Seventy‐five consecutive adult patients hospitalized for treatment of CAP were recruited in this single‐center cohort study. Doppler echocardiographic measurement of PASP was performed by 2 staff cardiologists. Follow‐up assessment was performed within 2 to 4 weeks of ending antibiotic treatment at radiographic resolution of CAP. Fifteen patients were excluded during follow‐up due to confirmation of chronic obstructive pulmonary disease.

Results

Pneumonia was unilateral in 40 (66.7%) and bilateral in 20 (33.3%) patients. Radiographic extent of pneumonia involved 2 pulmonary segments in 31 patients (51.7%), 3 to 5 pulmonary segments in 25 (41.7%), and 6 pulmonary segments in 4 patients (6.6%). ΔPASP between hospital admission and follow‐up correlated with the number of pulmonary segments involved (Rho = 0.953; P < .001) and PaO2 (Rho = −0.667; P < .001). The maximum PASP was greater during pneumonia than after resolution (34.82 ± 3.96 vs. 22.67 ± 4.04, P < .001).

Conclusions

Changes in PASP strongly correlated with radiological severity of CAP and PaO2. During pneumonia, PASP appeared increased without significant change in left ventricular filling pressures. This suggests that disease‐related changes in lung tissue caused by pneumonia may easily and reproducibly be assessed using conventional noninvasive bedside diagnostics such as echocardiography and arterial blood gas analysis.
Mediastinal ectopic thyroid diagnosed by endobronchial ultrasound‐guided transbronchial needle aspiration: Report of three cases
Authors: Ozturk Ayperi , Cicek Tugba , Aktas Zafer , Demirag Funda , Yilmaz Aydin
Published: September 2017

An ectopic thyroid gland results from the abnormal migration of the thyroid in the course of its development. Primary ectopic mediastinal thyroid is very rare and occurs in less than 1% of all goiters that can be surgically excised. Ectopic thyroid tissue has a characteristic sonographic appearance as smooth‐bordered, homogeneous, hypoechoic tissue with fine specular echoes. We report 3 cases of mediastinal ectopic thyroid diagnosed by endobronchial ultrasound‐guided transbrochial needle aspiration biopsy.
Polymorphisms in homologous recombination repair genes and the risk and survival of breast cancer
Authors: Liao Yu‐Huang , Ren Jun‐Ting , Zhang Wei , Zhang Zheng‐Zheng , Lin Ying , Su Feng‐Xi , Jia Wei‐Hua , Tang Lu‐Ying , Ren Ze‐Fang
Published: September 2017

Background

Immunoglobulin (Ig)A antibody of Epstein–Barr virus (EBV) was found to associate with breast cancer (BC), whereas IgA positivity was related to a series of genetic markers in the genes of homologous recombination repair system (HRRs). We assessed the associations of the polymorphisms in HRR genes with the risk and survival of BC.

Methods

A case–control study was conducted with 1551 bc cases and 1605 age‐matched healthy controls between October 2008 and March 2012 in the Guangzhou Breast Cancer Study (GZBCS), China, and the case population were followed up until 31 January 2016. Five single nucleotide polymorphisms of candidate genes in HRR system were genotyped. Odds ratios (ORs) and hazards ratios (HRs) were calculated using multivariate logistic regression and Cox proportional hazards regression to estimate the risk and prognostic effect, respectively.

Results

RFC1 rs6829064 (AA) was associated with an increased BC risk [OR = 1.35; 95% confidence interval (CI) = 1.06–1.73] compared to the wild genotype (GG). NRM rs1075496 (GT/TT versus GG) was associated with a worse progression‐free survival (PFS) and the HR was 1.34 (95% CI = 1.01–1.78), particularly among advanced patients. LIG3 rs1052536 (CT/TT versus CC) was associated with a better PFS and the HR was 0.70 (95% CI = 0.53–0.93). However, RAD54L rs1710286 and RPA1 rs11078676 were not observed to be associated with either the risk or survival of BC.

Conclusions

The findings of the present study suggest that the polymorphisms in HRR genes were associated with BC risk (RFC1 rs6829064) and prognosis (NRM rs1075496 and LIG3 rs1052536), whereas RAD54L rs1710286 and RPA1 rs11078676 had null associations with BC.
Age‐associated differences in clinical manifestations and laboratory parameters during a dengue virus type 4 outbreak in Argentina
Authors: Byrne Alana B. , Gutierrez Guillermo F. , Bruno Agostina , Córdoba María T. , Bono María M. , Polack Fernando P. , Talarico Laura B. , Quipildor Marcelo O.
Published: September 2017

Infection by any of the four dengue virus (DENV) serotypes produces a wide spectrum of clinical illness in humans. Differences in clinical manifestation and severity have been associated with secondary heterologous infection, patient age, and virus serotype. In this context, this retrospective study sought to analyze the presentation of dengue in patients during the 2014 DENV‐4 outbreak affecting the City of Orán, Salta Province, Argentina. Demographic data, clinical manifestations, and laboratory abnormalities of laboratory‐confirmed dengue patients were compared between age groups and between patients with and without warning signs. Of 301 patients with laboratory‐confirmed dengue, 37.9% presented dengue with warning signs. Although nearly half of all patients had secondary DENV infections, no severe dengue cases, or deaths were reported. Furthermore, no association was found between incidence of warning signs and pre‐existing immunity to DENV. Pediatric patients were least likely to present warning signs and showed significantly decreased risk of fever, retro‐orbital pain, arthalgia, diarrhea and thrombocytopenia, and higher risk of rash compared to older patients. Female patients of all ages were also at higher risk of developing several symptoms. The characterization of DENV‐4 infection in humans, a DENV serotype recently reported in Argentina, revealed differences in clinical manifestations, laboratory parameters and the presence/absence of warning signs based on age group. Further investigation of these age‐related differences should contribute to better assessment of dengue disease in at risk populations.