bluuebunny/crossref_metadata_2025 huggingface dataset:
p16INK4a overexpression as a predictor of survival in ocular surface squamous neoplasia
Authors: Chauhan Sheetal , Sen Seema , Sharma Anjana , Kashyap Seema , Tandon Radhika , Bajaj Mandeep S , Pushker Neelam , Vanathi Murugesan , Chauhan Shyam S
Published: March 2018

Aims

To evaluate the expression and methylation status of the p16INK4a gene in early and advanced American Joint Committee on Cancer (AJCC) stages of ocular surface squamous neoplasia (OSSN) and to correlate its association with clinicopathological features and survival.

Methods

Sixty-four (35 early and 29 advanced AJCC stage) patients with OSSN formed part of this study and were followed up for 36–58 (mean 48±3.6) months. Immunohistochemical expression of the p16INK4a protein and methylation status of the p16INK4a gene were determined by methylation-specific PCR.

Results

Overexpression of p16INK4a was observed in 18/64 (28%) and hypermethylation in 35/64 (54.7%) OSSN cases. A gradual significant increase in the expression of p16INK4a (0%–48%, P=0.03) and decrease in its methylation (75%–16%, P=0.001) was observed with disease progression from early to advanced tumour stage. Overexpression of p16INK4a was significantly associated with palpebral location and diffuse growth pattern in both early and advanced T stage. Hypermethylation of p16INK4a was significantly associated with history of longer sunlight exposure in both early and advanced T stage of OSSN cases. In advanced T stage, p16INK4a overexpression was associated with reduced disease-free survival (P=0.02) and poor prognosis (HR, 0.2; P=0.03).

Conclusions

OSSN patients presenting at an advanced AJCC stage with p16INK4a overexpression may require more aggressive treatment. Epigenetic inactivation of the p16INK4a gene due to sunlight exposure could be responsible for pathogenesis of OSSN.
Human rights versus societal norms: a mixed methods study among healthcare providers on social stigma related to adolescent abortion and contraceptive use in Kisumu, Kenya
Authors: Håkansson Miranda , Oguttu Monica , Gemzell-Danielsson Kristina , Makenzius Marlene
Published: March 2018

Introduction

Adolescent pregnancy represents a serious public health issue in sub-Saharan Africa, and stigmatising attitudes are contributing factors. This study investigates stigmatising attitudes related to adolescent pregnancy, abortion and contraceptive use among healthcare providers working with postabortion care (PAC) in a low-resource setting in Kenya.

Methods

A mixed methods approach in a convergent design was utilised to capture attitudes related to abortion and contraceptive use among 86 (f=62; m=19) PAC providers in Kisumu, Kenya. Two Likert-scale questionnaires were used: the 18-item Stigmatising Attitudes, Beliefs and Actions Scale (SABAS) and the 7-item Contraceptive Use Stigma Scale (CUSS). 74 PAC providers responded to the SABAS, 44 to the CUSS and 12 participated in two focus group discussions. Descriptive statistics, psychometric tests of instruments and qualitative content analysis were conducted and reported in accordance with Consolidated Criteria for Reporting Qualitative Research.

Results

Cronbach’s α coefficients for the total instrument was 0.88 (SABAS) and 0.84 (CUSS). The majority, 92% (68/74) agreed that a woman who has had an abortion should be treated equally to everyone else, 27% (20/74) considered abortion a sin and 30% (22/74) believed she will make abortion a habit. Contraceptive use among adolescent women was associated with promiscuity (39%; 17/44), hence contraceptives should only be available to married women (36%; 16/44), and 20% (9/44) believed that contraceptive use causes infertility. The providers encouraged women’s autonomy and their rights to sexual and reproductive health; however, unclear regulations reinforce religious and cultural beliefs, which hampers implementation of evidence-based contraceptive counselling.

Conclusion

Stigmatising attitudes towards young women in need of abortion and contraception is common among PAC providers. Their work is characterised by a conflict between human rights and societal norms, thus highlighting the need for interventions targeting PAC providers to reduce stigma and misconceptions related to abortion and contraception among adolescent women.
Relationship between stress-related psychosocial work factors and suboptimal health among Chinese medical staff: a cross-sectional study
Authors: Liang Ying-Zhi , Chu Xi , Meng Shi-Jiao , Zhang Jie , Wu Li-Juan , Yan Yu-Xiang
Published: March 2018

Objectives

The study aimed to develop and validate a model to measure psychosocial factors at work among medical staff in China based on confirmatory factor analysis (CFA). The second aim of the current study was to clarify the association between stress-related psychosocial work factors and suboptimal health status.

Design

The cross-sectional study was conducted using clustered sampling method.

Setting

Xuanwu Hospital, a 3A grade hospital in Beijing.

Participants

Nine hundred and fourteen medical staff aged over 40 years were sampled. Seven hundred and ninety-seven valid questionnaires were collected and used for further analyses. The sample included 94% of the Han population.

Main outcome measures

The Copenhagen Psychosocial Questionnaire (COPSOQ) and the Suboptimal Health Status Questionnaires-25 were used to assess the psychosocial factors at work and suboptimal health status, respectively. CFA was conducted to establish the evaluating method of COPSOQ. A multivariate logistic regression model was used to estimate the relationship between suboptimal health status and stress-related psychosocial work factors among Chinese medical staff.

Results

There was a strong correlation among the five dimensions of COPSOQ based on the first-order factor model. Then, we established two second-order factors including negative and positive psychosocial work stress factors to evaluate psychosocial factors at work, and the second-order factor model fit well. The high score in negative (OR (95% CI)=1.47 (1.34 to 1.62), P<0.001) and positive (OR (95% CI)=0.96 (0.94 to 0.98), P<0.001) psychosocial work factors increased and decreased the risk of suboptimal health, respectively. This relationship remained statistically significant after adjusting for confounders and when using different cut-offs of suboptimal health status.

Conclusions

Among medical staff, the second-order factor model was a suitable method to evaluate the COPSOQ. The negative and positive psychosocial work stress factors might be the risk and protective factors of suboptimal health, respectively. Moreover, negative psychosocial work stress was the most associated factor to predict suboptimal health.
Factor structure and convergent validity of the Derriford Appearance Scale-24 using standard scoring versus treating ‘not applicable’ responses as missing data: a Scleroderma Patient-centered Intervention Network (SPIN) cohort study
Authors: Merz Erin L , Kwakkenbos Linda , Carrier Marie-Eve , Gholizadeh Shadi , Mills Sarah D , Fox Rina S , Jewett Lisa R , Williamson Heidi , Harcourt Diana , Assassi Shervin , Furst Daniel E , Gottesman Karen , Mayes Maureen D , Moss Tim P , Thombs Brett D , Malcarne Vanessa L
Published: March 2018

Objective

Valid measures of appearance concern are needed in systemic sclerosis (SSc), a rare, disfiguring autoimmune disease. The Derriford Appearance Scale-24 (DAS-24) assesses appearance-related distress related to visible differences. There is uncertainty regarding its factor structure, possibly due to its scoring method.

Design

Cross-sectional survey.

Setting

Participants with SSc were recruited from 27 centres in Canada, the USA and the UK. Participants who self-identified as having visible differences were recruited from community and clinical settings in the UK.

Participants

Two samples were analysed (n=950 participants with SSc; n=1265 participants with visible differences).

Primary and secondary outcome measures

The DAS-24 factor structure was evaluated using two scoring methods. Convergent validity was evaluated with measures of social interaction anxiety, depression, fear of negative evaluation, social discomfort and dissatisfaction with appearance.

Results

When items marked by respondents as ‘not applicable’ were scored as 0, per standard DAS-24 scoring, a one-factor model fit poorly; when treated as missing data, the one-factor model fit well. Convergent validity analyses revealed strong correlations that were similar across scoring methods.

Conclusions

Treating ‘not applicable’ responses as missing improved the measurement model, but did not substantively influence practical inferences that can be drawn from DAS-24 scores. Indications of item redundancy and poorly performing items suggest that the DAS-24 could be improved and potentially shortened.
Systematic review and meta-analysis of global birth prevalence of clubfoot: a study protocol
Authors: Ansar Adnan , Rahman Ahmed Ehsanur , Romero Lorena , Haider Mohammad Rifat , Rahman Mohammad Masudur , Moinuddin Md , Siddique Md Abu Bakkar , Mamun Md Al , Mazumder Tapas , Pirani Shafique Pyarali , Mathias Richard Gordon , Arifeen Shams EI , Hoque Dewan Md Emdadul
Published: March 2018

Introduction

Clubfoot is a common congenital birth defect, with an average prevalence of approximately 1 per 1000 live births, although this rate is reported to vary among different countries around the world. If it remains untreated, clubfoot causes permanent disability, limits educational and employment opportunities, and personal growth. The aim of this systematic review and meta-analysis is to estimate the global birth prevalence of congenital clubfoot.

Methods and analysis

Electronic databases including MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, Global Health, Latin American & Caribben Health Science Literature (LILACS), Maternity and Infant Care, Web of Science, Scopus and Google Scholar will be searched for observational studies based on predefined criteria and only in English language from inception of database in 1946 to 10 November 2017. A standard data extraction form will be used to extract relevant information from included studies. The Joanna Briggs Institute appraisal checklist will be used to assess the overall quality of studies reporting prevalence. All included studies will be assessed for risk of bias using a tool developed specifically for prevalence studies. Forest plots will be created to understand the overall random effects of pooled estimates with 95% CIs. An I2test will be done for heterogeneity of the results (P>0.05), and to identify the source of heterogeneity across studies, subgroup or meta-regression will be used to assess the contribution of each variable to the overall heterogeneity. A funnel plot will be used to identify reporting bias, and sensitivity analysis will be used to assess the impact of methodological quality, study design, sample size and the impact of missing data.

Ethics and dissemination

This review will be conducted completely based on published data, so approval from an ethics committee or written consent will not be required. The results will be disseminated through a peer-reviewed publication and relevant conference presentations.

PROSPERO registration number

CRD42016041922.
Measurement and monitoring of safety: impact and challenges of putting a conceptual framework into practice
Authors: Chatburn Eleanor , Macrae Carl , Carthey Jane , Vincent Charles
Published: March 2018

Background

The Measurement and Monitoring of Safety Framework provides a conceptual model to guide organisations in assessing safety. The Health Foundation funded a large-scale programme to assess the value and impact of applying the Framework in regional and frontline care settings. We explored the experiences and reflections of key participants in the programme.

Methods

The study was conducted in the nine healthcare organisations in England and Scotland testing the Framework (three regional improvement bodies, six frontline settings). Post hoc interviews with clinical and managerial staff were analysed using template analysis.

Findings

Participants reported that the Framework promoted a substantial shift in their thinking about how safety is actively managed in their environment. It provided a common language, facilitated a more inquisitive approach and encouraged a more holistic view of the components of safety. These changes in conceptual understanding, however, did not always translate into broader changes in practice, with many sites only addressing some aspects of the Framework. One of the three regions did embrace the Framework in its entirety and achieved wider impact with a range of interventions. This region had committed leaders who took time to fully understand the concepts, who maintained a flexible approach to exploring the utility of the Framework and who worked with frontline staff to translate the concepts for local settings.

Conclusions

The Measuring and Monitoring of Safety Framework has the potential to support a broader and richer approach to organisational safety. Such a conceptually based initiative requires both committed leaders who themselves understand the concepts and more time to establish understanding and aims than might be needed in a standard improvement programme.
Use of a modified thromboelastography assay for the detection of hyperfibrinolysis in a dog infected with Angiostrongylus vasorum
Authors: Cole Laura , Barfield Dominic , Chan Daniel L , Cortellini Stefano
Published: March 2018

A dog presenting with scleral haemorrhage and neck pain was diagnosed with Angiostrongylus vasorum on direct faecal smear. Thromboelastography (with the addition of tissue plasminogen activator) revealed evidence of hypocoagulability and hyperfibrinolysis. The administration of fresh frozen plasma and tranexamic acid was associated with the resolution of a hypocoagulable and a hyperfibrinolytic state, as well as clinical improvement.
First-principles study of bandgap tuning in Ge1−xPbxSe
Authors: Lohani Himanshu
Published: March 2018

Narrow bandgap and its tuning are important aspects of materials for their technological applications. In this context group IV–VI semiconductors are one of the interesting candidates. In this paper, we explore the possibility of bandgap tuning in one of the family member of this family GeSe by using isoelectronic Pb doping. Our study is first-principles based electronic structure calculations of Ge[Formula: see text]Pb[Formula: see text]Se. This study reveals that the Ge-p and Se-p states are strongly hybridized in GeSe and shows a gap in the DOS at Ef in GeSe. This gap reduces systematically with simultaneous enhancement of the states in the near Ef region as a function of Pb doping. This leads tuning of the indirect bandgap in GeSe via Pb doping. The results of the indirect bandgap decrement are consistent with the experimental findings. We propose a mechanism where the electrostatic effect of dopant Pb cation could be responsible for these changes in the electronic structure of GeSe.
Generic and Specific Impressions Estimation and Their Application to KANSEI-Based Clothing Fabric Image Retrieval
Authors: Chen Yen-Wei , Huang Xinyin , Chen Dingye , Han Xian-Hua
Published: March 2018

Current image retrieval techniques are mainly based on text or visual contents. However, both text-based and contents-based methods lack the capability of utilizing human intuition and KANSEI (impression). In this paper, we proposed an impression-based image retrieval method in order to realize the image retrieval according to our impression presented by impression keywords. We first propose a generic and specific impressions estimation method based on machine learning and then apply it to impression-based clothing fabric image retrieval. We use a semantic differential (SD) method to measure the user’s impressions such as brightness and warmth while they view a cloth fabric image. We also extract both global and local features of cloth fabric images such as color and texture using computer vision techniques. Then we use support vector regression to model the mapping functions between the generic impression (or specific impression) and image features. The learnt mapping functions are used to estimate the generic and specific impressions of cloth fabric images. The retrieval is done by comparing the query impression with the estimated impression of images in the database.
Emerging Topics on Disseminated Cancer Cell Dormancy and the Paradigm of Metastasis
Authors: Aguirre-Ghiso Julio A. , Sosa Maria Soledad
Published: March 2018

Disseminated tumor cells (DTCs) are recognized as the seeds of metastasis. However, metastatic lesions can become symptomatic years or decades after primary tumor removal. This clinical finding suggests that DTCs are not immediately competent to initiate growth and can persist in a dormant state. Here we review recent data for three potential scenarios that could result in DTC dormancy: (a) The target organ microenvironment instructs DTCs to enter dormancy; (b) primary tumors pre-encode a dormancy signature that only becomes evident when DTCs enter target organs that produce dormancy-inducing cues; and (c) early dissemination spawns DTCs that, by virtue of being closely related to normal cells, would retain the capacity to respond to dormancy-instructing signals and enter dormancy in target organs. The literature supports the existence of these scenarios and provides insight into how to prevent metastasis. Importantly, cotargeting dormant and proliferative DTCs in stage IV cancer may also improve outcomes in this clinical setting.
Insulin uptake and action in microvascular endothelial cells of lymphatic and blood origin
Authors: Jaldin-Fincati Javier R. , Pereira Rafaela V. S. , Bilan Philip J. , Klip Amira
Published: March 2018

Whereas the blood microvasculature constitutes a biological barrier to the action of blood-borne insulin on target tissues, the lymphatic microvasculature might act as a barrier to subcutaneously administrated insulin reaching the circulation. Here, we evaluate the interaction of insulin with primary microvascular endothelial cells of lymphatic [human dermal lymphatic endothelial cells (HDLEC)] and blood [human adipose microvascular endothelial cells (HAMEC)] origin, derived from human dermal and adipose tissues, respectively. HDLEC express higher levels of insulin receptor and signal in response to insulin as low as 2.5 nM, while HAMEC only activate signaling at 100 nM (a dose that blood vessels do not normally encounter). Low insulin acts specifically through the insulin receptor, while supraphysiological insulin acts through both the IR and insulin growth factor-1 receptor. At supraphysiological or injection site-compatible doses pertinent to lymphatic microvessels, insulin enters HAMEC and HDLEC via fluid-phase endocytosis. Conversely, at physiologically circulating doses (0.2 nM) pertinent to blood microvessels, insulin enters HAMEC through a receptor-mediated process requiring IR autophosphorylation but not downstream insulin signaling. At physiological doses, internalized insulin is barely degraded and is instead released intact to the extracellular medium. In conclusion, we document for the first time the mechanism of interaction of insulin with lymphatic endothelial cells, which may be relevant to insulin absorption during therapeutic injections. Furthermore, we describe distinct action and uptake routes for insulin at physiological and supraphysiological doses in blood microvascular endothelial cells, providing a potential explanation for previously conflicting studies on endothelial insulin uptake.
Assessment of hepatic insulin extraction from in vivo surrogate methods of insulin clearance measurement
Authors: Asare-Bediako Isaac , Paszkiewicz Rebecca L. , Kim Stella P. , Woolcott Orison O. , Kolka Cathryn M. , Burch Miguel , Kabir Morvarid , Piccinini Francesca , Bergman Richard N.
Published: March 2018

Hyperinsulinemia, accompanied by reduced first-pass hepatic insulin extraction (FPE) and increased secretion, is a primary response to insulin resistance. Different in vivo methods are used to estimate the clearance of insulin, which is assumed to reflect FPE. We compared two methodologically different but commonly used indirect estimates with directly measured FPE in healthy dogs ( n = 9). The indirect methods were 1) metabolic clearance rate of insulin (MCR) during the hyperinsulinemic-euglycemic clamp (EGC), a steady-state method, and 2) fractional clearance rate of insulin (FCR) during the frequently sampled intravenous glucose tolerance test (FSIGT), a dynamic method. MCR was calculated as the ratio of insulin infusion rate to steady-state plasma insulin. FCR was calculated as the exponential decay rate constant of the injected insulin. Directly measured FPE is based on the difference in insulin measurements during intraportal vs. peripheral vein insulin infusions. We found a strong correlation between indirect FCR (min−1) and FPE (%). In contrast, we observed a poor association between MCR (ml·min−1·kg−1) and FPE (%). Our findings in canines suggest that FCR measured during FSIGT can be used to estimate FPE. However, MCR calculated during EGC appears to be a poor surrogate for FPE.
Developmental origins of nonalcoholic fatty liver disease as a risk factor for exaggerated metabolic and cardiovascular-renal disease
Authors: Spradley Frank T. , Smith Jillian A. , Alexander Barbara T. , Anderson Christopher D.
Published: March 2018

Intrauterine growth restriction (IUGR) is linked to increased risk for chronic disease. Placental ischemia and insufficiency in the mother are implicated in predisposing IUGR offspring to metabolic dysfunction, including hypertension, insulin resistance, abnormalities in glucose homeostasis, and nonalcoholic fatty liver disease (NAFLD). It is unclear whether these metabolic disturbances contribute to the developmental origins of exaggerated cardiovascular-renal disease (CVRD) risk accompanying IUGR. IUGR impacts the pancreas, adipose tissue, and liver, which are hypothesized to program for hepatic insulin resistance and subsequent NAFLD. NAFLD is projected to become the major cause of chronic liver disease and contributor to uncontrolled type 2 diabetes mellitus, which is a leading cause of chronic kidney disease. While NAFLD is increased in experimental models of IUGR, lacking is a full comprehension of the mechanisms responsible for programming of NAFLD and whether this potentiates susceptibility to liver injury. The use of well-established and clinically relevant rodent models, which mimic the clinical characteristics of IUGR, metabolic disturbances, and increased blood pressure in the offspring, will permit investigation into mechanisms linking adverse influences during early life and later chronic health. The purpose of this review is to propose mechanisms, including those proinflammatory in nature, whereby IUGR exacerbates the pathogenesis of NAFLD and how these adverse programmed outcomes contribute to exaggerated CVRD risk. Understanding the etiology of the developmental origins of chronic disease will allow investigators to uncover treatment strategies to intervene in the mother and her offspring to halt the increasing prevalence of metabolic dysfunction and CVRD.
Endoscopic Submucosal Tunnel Dissection for Large Gastric Neoplastic Lesions: A Case-Matched Controlled Study
Authors: Feng Xiuxue , Linghu Enqiang , Chai Ningli , Lu Zhongsheng , Wang Xiangdong , Tang Ping , Meng Jiangyun , Du Hong , Wang Hongbin
Published: March 2018

Aim. To evaluate the efficacy and safety of endoscopic submucosal tunnel dissection (ESTD) for resection of large superficial gastric lesions (SGLs). Methods. The clinicopathological records of patients performed with ESTD or endoscopic submucosal dissection (ESD) for SGLs between January 2012 and January 2014 were retrospectively reviewed. 7 cases undergoing ESTD were enrolled to form the ESTD group. The cases were individually matched at a 1 : 1 ratio to other patients performed with ESD according to lesion location, ulcer or scar findings, resected specimen area, operation time and operators, and the matched cases constituting the ESD group. The treatment outcomes were compared between the two groups. Results. The mean specimen size was 46 mm. 10 lesions were located in the cardia and 4 lesions in the lesser curvature of the lower gastric body. En bloc resection was achieved for all lesions. The mean ESTD resection time was 69 minutes as against 87.7 minutes for the ESD (P=0.01). The mean resection speed was faster for ESTD than for ESD (18.86 mm2/min versus 13.76 mm2/min, P=0.03). There were no significant differences regarding the safety and curability during the endoscopic follow-up (mean 27 months). Conclusions. ESTD is effective and safe for the removal of SGLs and appears to be an optimal option for patients with large SGLs at suitable sites.
Clustering Pattern and Functional Effect of SNPs in Human miRNA Seed Regions
Authors: He Sha , Ou Haiyan , Zhao Cunyou , Zhang Jian
Published: March 2018

miRNAs are a class of noncoding RNAs important in posttranscriptional repressors and involved in the regulation of almost every biological process by base paring with target genes through sequence in their seed regions. Genetic variations in the seed regions have vital effects on gene expression, phenotypic variation, and disease susceptibility in humans. The distribution pattern of genetic variation in miRNA seed regions might be related to miRNA function and is worth paying more attention to. We here employed computational analyses to explore the clustering pattern and functional effect of SNPs in human miRNA seed regions. A total of 1879 SNPs were mapped to 1226 human miRNA seed regions. We found that miRNAs with SNPs in their seed region are significantly enriched in miRNA clusters. We also found that SNPs in clustered miRNA seed regions have a lower functional effect than have SNPs in nonclustered miRNA seed regions. Additionally, we found that clustered miRNAs with SNPs in seed regions are involved in more pathways. Overall, our results demonstrate that SNPs in clustered miRNA seed regions can take part in more intricate and complex gene-regulating networks with lower functional cost by functional complementarity. Moreover, our results also broaden current knowledge on the genetic variation in human miRNA seed regions.
Adaptive Learning Based Tracking Control of Marine Vessels with Prescribed Performance
Authors: Xu Zhao , Ge Shuzhi Sam , Hu Changhua , Hu Jinwen
Published: March 2018

A novel adaptive tracking controller of fully actuated marine vessels is proposed with completely unknown dynamics and external disturbances. The model of dominant dynamic behaviors and unknown disturbances of the vessel are learned by a neural network in real time. The controller is designed and it unifies backstepping and adaptive neural network techniques with predefined tracking performance constraints on the tracking convergence rate and the transient and steady-state tracking error. The stability of the proposed adaptive tracking controller of the vessel is proven with a uniformly bounded tracking error. The proposed adaptive tracking controller is shown to be effective in the tracking control of marine vessels by simulations.
Baicalein Accelerates Tendon-Bone Healing via Activation of Wnt/β-Catenin Signaling Pathway in Rats
Authors: Tian Xinggui , Jiang Huaji , Chen Yuhui , Ao Xiang , Chen Chuan , Zhang Wentao , He Feilin , Liao Xiaoqing , Jiang Xiaocheng , Li Tao , Zhang Zhongmin , Zhang Xintao
Published: March 2018

Background. Tendon-bone healing is a reconstructive procedure which requires a tendon graft healing to a bone tunnel or to the surface of bone after the junction injury between tendon, ligament, and bone. The surgical reattachment of tendon to bone often fails due to regeneration failure of the specialized tendon-bone junction. Materials and Methods. An extra-articular tendon-bone healing rat model was established to discuss the effect of the baicalein 10 mg/(kg·d) in accelerating tendon-bone healing progress. Also, tendon-derived stem cells (TDSCs) were treated with various concentrations of baicalein or dickkopf-1 (DKK-1) to stimulate differentiation for 14 days. Results. In vivo, tendon-bone healing strength of experiment group was obviously stronger than the control group in 3 weeks as well as in 6 weeks. And there were more mature fibroblasts, more Sharpey fibers, and larger new bone formation area treated intragastrically with baicalein compared with rats that were treated with vehicle for 3 weeks and 6 weeks. In vitro, after induction for 14 days, the expressions of osteoblast differentiation markers, that is, alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), osteocalcin (OCN), osterix (OSX), and collagen I, were upregulated and Wnt/β-catenin signaling pathway was enhanced in TDSCs. The effect of DKK-1 significantly reduced the effect of baicalein on the osteogenic differentiation. Conclusion. These data suggest that baicalein may stimulate TDSCs osteogenic differentiation via activation of Wnt/β-catenin signaling pathway to accelerate tendon-bone healing.
Efficiency Analysis of Government Subsidy and Performance Guarantee Policies in Relation to PPP Infrastructure Projects
Authors: Shi Lei , He Yujia , Onishi Masamitsu , Kobayashi Kiyoshi
Published: March 2018

Sustainable operation of public-private partnership (PPP) infrastructure projects that are characterized by considerable external benefits is of vital importance. However, a liquidity shock might trigger an inefficient liquidation of a project by the special purpose vehicle (SPV) and the bank, whose objectives are to maximize the profits generated by the project. This study argues that performance guarantee and subsidy policies implemented by the government play a role in encouraging socially efficient decision-making by the SPV and the bank to ensure the continuation of socially valuable projects. The results show that both government subsidy and performance guarantee policies are effective in avoiding the inefficient liquidation of PPP infrastructure projects when the external benefits are large and certain. However, a performance guarantee policy might lead to inefficient continuation when the external benefits of a project are uncertain. Finally, we discuss the possibility that an integrated policy combining performance guarantees and government subsidies improves the efficiency of a PPP infrastructure project.
Optimized Extract from Corylopsis coreana Uyeki (Hamamelidaceae) Flos Inhibits Osteoclast Differentiation
Authors: Lee Yongjin , Kim Jung-Eun , Kim Kwang-Jin , Cho Seung-Sik , Son Young-Jin
Published: March 2018

Osteoporosis is a metabolic disorder that decreases the stability against fractures of the spine, femur, and radius by weakening the strength and integrity of bones. Receptor activator of nuclear factor‐kappa B ligand signaling ultimately activated nuclear factor‐activated T cells c1, a major transcription factor for osteoclast formation. This study researched the effects of Corylopsis coreana (C. coreana) Uyeki flos extracts on the antiosteoclastic potential of macrophages and the phytochemicals contained therein. The alcoholic extract of C. coreana Uyeki flos inhibited the differentiation of osteoclast. We carried out the experiments of the pattern of differentiation of osteoclasts based on the alcoholic percentage of extracts. Among them, 80% alcoholic extract showed the highest inhibitory effect. The alcoholic extract was composed of phytochemicals such as bergenin, quercetin, and quercitrin. This extract inhibited not only mRNA expression levels of NFATc1, osteoclast‐associated receptor (OSCAR), cathepsin K, and tartrate‐resistant acid phosphatase (TRAP), but also the translational expression of NFATc1. The inhibitory effect for osteoclast differentiation of the alcoholic extract was confirmed using the resorption pit assay. This is the first scientific report of the antiosteoclastic effects of C. coreana Uyeki flos extract, which can be applied therapeutically for the treatment of osteoporosis.
Quantum Gravity Effect on the Tunneling Particles from 2 + 1-Dimensional New-Type Black Hole
Authors: Gecim Ganim , Sucu Yusuf
Published: March 2018

We investigate the generalized uncertainty principle (GUP) effect on the Hawking temperature for the 2 + 1-dimensional new-type black hole by using the quantum tunneling method for both the spin-1/2 Dirac and the spin-0 scalar particles. In computation of the GUP correction for the Hawking temperature of the black hole, we modified Dirac and Klein-Gordon equations. We observed that the modified Hawking temperature of the black hole depends not only on the black hole properties, but also on the graviton mass and the intrinsic properties of the tunneling particle, such as total angular momentum, energy, and mass. Also, we see that the Hawking temperature was found to be probed by these particles in different manners. The modified Hawking temperature for the scalar particle seems low compared with its standard Hawking temperature. Also, we find that the modified Hawking temperature of the black hole caused by Dirac particle’s tunneling is raised by the total angular momentum of the particle. It is diminishable by the energy and mass of the particle and graviton mass as well. These intrinsic properties of the particle, except total angular momentum for the Dirac particle, and graviton mass may cause screening for the black hole radiation.
Electrochemical Solvent Cointercalation into Graphite in Propylene Carbonate-Based Electrolytes: A Chronopotentiometric Characterization
Authors: Song Hee-Youb , Jeong Soon-Ki
Published: March 2018

Interfacial reactions strongly influence the performance of lithium-ion batteries, with the main interfacial reaction between graphite and propylene carbonate- (PC-) based electrolytes corresponding to solvent cointercalation. Herein, the redox reactions of solvated lithium ions occurring at the graphite interface in 1 M·LiClO4/PC were probed by chronopotentiometry, in situ atomic force microscopy (AFM), and in situ Raman spectroscopy. The obtained results revealed that high coulombic efficiency (97.5%) can be achieved at high current density, additionally showing the strong influence of charge capacity on the above redox reactions. Moreover, AFM imaging indicated the occurrence of solvent cointercalation during the first reduction, as reflected by the presence of hills and blisters on the basal plane of highly oriented pyrolytic graphite subjected to the above process.
Loss of the Nuclear Pool of Ubiquitin Ligase CHIP/STUB1 in Breast Cancer Unleashes the MZF1-Cathepsin Pro-oncogenic Program
Authors: Luan Haitao , Mohapatra Bhopal , Bielecki Timothy A. , Mushtaq Insha , Mirza Sameer , Jennings Tameka A. , Clubb Robert J. , An Wei , Ahmed Dena , El-Ansari Rokaya , Storck Matthew D. , Mishra Nitish K. , Guda Chittibabu , Sheinin Yuri M. , Meza Jane L. , Raja Srikumar , Rakha Emad A. , Band Vimla , Band Hamid
Published: March 2018

CHIP/STUB1 ubiquitin ligase is a negative co-chaperone for HSP90/HSC70, and its expression is reduced or lost in several cancers, including breast cancer. Using an extensive and well-annotated breast cancer tissue collection, we identified the loss of nuclear but not cytoplasmic CHIP to predict more aggressive tumorigenesis and shorter patient survival, with loss of CHIP in two thirds of ErbB2+ and triple-negative breast cancers (TNBC) and in one third of ER+ breast cancers. Reduced CHIP expression was seen in breast cancer patient-derived xenograft tumors and in ErbB2+ and TNBC cell lines. Ectopic CHIP expression in ErbB2+ lines suppressed in vitro oncogenic traits and in vivo xenograft tumor growth. An unbiased screen for CHIP-regulated nuclear transcription factors identified many candidates whose DNA-binding activity was up- or downregulated by CHIP. We characterized myeloid zinc finger 1 (MZF1) as a CHIP target, given its recently identified role as a positive regulator of cathepsin B/L (CTSB/L)-mediated tumor cell invasion downstream of ErbB2. We show that CHIP negatively regulates CTSB/L expression in ErbB2+ and other breast cancer cell lines. CTSB inhibition abrogates invasion and matrix degradation in vitro and halts ErbB2+ breast cancer cell line xenograft growth. We conclude that loss of CHIP remodels the cellular transcriptome to unleash critical pro-oncogenic pathways, such as the matrix-degrading enzymes of the cathepsin family, whose components can provide new therapeutic opportunities in breast and other cancers with loss of CHIP expression.

Significance: These findings reveal a novel targetable pathway of breast oncogenesis unleashed by the loss of tumor suppressor ubiquitin ligase CHIP/STUB1. Cancer Res; 78(10); 2524–35. ©2018 AACR.
Tight Junction Protein Claudin-2 Promotes Self-Renewal of Human Colorectal Cancer Stem-like Cells
Authors: Paquet-Fifield Sophie , Koh Shir Lin , Cheng Lesley , Beyit Laura M. , Shembrey Carolyn , Mølck Christina , Behrenbruch Corina , Papin Marina , Gironella Meritxell , Guelfi Sophie , Nasr Ramona , Grillet Fanny , Prudhomme Michel , Bourgaux Jean-Francois , Castells Antoni , Pascussi Jean-Marc , Heriot Alexander G. , Puisieux Alain , Davis Melissa J. , Pannequin Julie , Hill Andrew F. , Sloan Erica K. , Hollande Frédéric
Published: March 2018

Posttreatment recurrence of colorectal cancer, the third most lethal cancer worldwide, is often driven by a subpopulation of cancer stem cells (CSC). The tight junction (TJ) protein claudin-2 is overexpressed in human colorectal cancer, where it enhances cell proliferation, colony formation, and chemoresistance in vitro. While several of these biological processes are features of the CSC phenotype, a role for claudin-2 in the regulation of these has not been identified. Here, we report that elevated claudin-2 expression in stage II/III colorectal tumors is associated with poor recurrence-free survival following 5-fluorouracil–based chemotherapy, an outcome in which CSCs play an instrumental role. In patient-derived organoids, primary cells, and cell lines, claudin-2 promoted colorectal cancer self-renewal in vitro and in multiple mouse xenograft models. Claudin-2 enhanced self-renewal of ALDHHigh CSCs and increased their proportion in colorectal cancer cell populations, limiting their differentiation and promoting the phenotypic transition of non-CSCs toward the ALDHHigh phenotype. Next-generation sequencing in ALDHHigh cells revealed that claudin-2 regulated expression of nine miRNAs known to control stem cell signaling. Among these, miR-222-3p was instrumental for the regulation of self-renewal by claudin-2, and enhancement of this self-renewal required activation of YAP, most likely upstream from miR-222-3p. Taken together, our results indicate that overexpression of claudin-2 promotes self-renewal within colorectal cancer stem-like cells, suggesting a potential role for this protein as a therapeutic target in colorectal cancer.

Significance: Claudin-2-mediated regulation of YAP activity and miR-222-3p expression drives CSC renewal in colorectal cancer, making it a potential target for therapy. Cancer Res; 78(11); 2925–38. ©2018 AACR.
Estrogen Metabolism in Premenopausal Women Is Related to Early Life Body Fatness
Authors: Houghton Lauren C. , Sisti Julia S. , Hankinson Susan E. , Xie Jing , Xu Xia , Hoover Robert N. , Eliassen A. Heather , Ziegler Regina G.
Published: March 2018

Background: Estrogen metabolism in premenopausal women may be related to early life body fatness.

Methods: Premenopausal women participating in the Nurses' Health Study II recalled their body fatness at ages 5, 10, and 20 years using a validated 9-level pictogram. Fifteen estrogens and estrogen metabolites (EM) were measured using LC/MS-MS in luteal phase urines from 603 women ages 32–54 years. Geometric means of individual EM, metabolic pathway groups, and pathway ratios were examined by body fatness categories using linear mixed models.

Results: Body fatness at each age was inversely associated with adult concentrations of all EM combined, parent estrogens (estrone, estradiol), and the 2-hydroxylation pathway. Women in the top (vs. bottom) category of body fatness at age 10 had 21% lower levels of all EM (Ptrend = 0.003), 24% lower parent estrogens (Ptrend = 0.002), and 36% lower 2-pathway (Ptrend = 0.0003). Body fatness at age 10 was inversely associated with 2-catechols (35% lower, Ptrend = 0.0004) and 2-methylated catechols (30% lower, Ptrend = 0.002). After adjusting for premenopausal body mass index (BMI), these associations remained inverse but were attenuated; only parent estrogens remained statistically significant (21% lower, Ptrend = 0.01). Body fatness at ages 5 and 20 were similarly, but more weakly, associated with estrogen pathways.

Conclusions: Estimates of body fatness during early life were inversely associated with premenopausal levels of all EM combined, parent estrogens, and 2-pathway estrogen metabolites. These relationships were not fully explained by adult BMI.

Impact: These findings inform investigations of diseases linked to early life body fatness and estrogen metabolism. Cancer Epidemiol Biomarkers Prev; 27(5); 585–93. ©2018 AACR.
Metformin Is Not Associated with Incidence Risk of Non-Hodgkin Lymphomas among Diabetic Patients
Authors: Ye Xibiao , Zhang Geng , Righolt Christiaan , Johnston James B. , Banerji Versha , Gibson Spencer B. , Mahmud Salaheddin M.
Published: March 2018

Background: Several epidemiological studies have shown a positive association between diabetes and increased risk of non-Hodgkin lymphoma (NHL), but the effect of diabetic treatment drugs such as metformin on the risk is unknown.

Methods: We conducted a population-based nested case–control study involving 878 NHL cases and 4,364 controls diagnosed with diabetes. Use of metformin and other medications before diagnosis and medical condition histories were assessed using administrative databases. We used conditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for use of metformin, adjusting for confounders.

Results: Risk of total NHLs is not associated with ever use of metformin (OR, 0.93; 95% CI, 0.79–1.10) among diabetic patients. NHL subtypes were also not associated with metformin use.

Conclusions: Metformin use is not associated with overall or subtype NHL risk among diabetic patients.

Impact: NHLs are etiologically heterogeneous and larger scale studies are warranted to test the potential effect of metformin by NHL subtype. Cancer Epidemiol Biomarkers Prev; 27(5); 610–2. ©2018 AACR.
Physiological and Molecular Effects of in vivo and ex vivo Mild Skin Barrier Disruption
Authors: Pfannes Eva K.B. , Weiss Lina , Hadam Sabrina , Gonnet Jessica , Combardière Béhazine , Blume-Peytavi Ulrike , Vogt Annika
Published: March 2018

The success of topically applied treatments on skin relies on the efficacy of skin penetration. In order to increase particle or product penetration, mild skin barrier disruption methods can be used. We previously described cyanoacrylate skin surface stripping as an efficient method to open hair follicles, enhance particle penetration, and activate Langerhans cells. We conducted ex vivo and in vivo measurements on human skin to characterize the biological effect and quantify barrier disruption-related inflammation on a molecular level. Despite the known immunostimulatory effects, this barrier disruption and hair follicle opening method was well accepted and did not result in lasting changes of skin physiological parameters, cytokine production, or clinical side effects. Only in ex vivo human skin did we find a discrete increase in IP-10, TGF-β, IL-8, and GM-CSF mRNA. The data underline the safety profile of this method and demonstrate that the procedure per se does not cause substantial inflammation or skin damage, which is also of interest when applied to non-invasive sampling of biomarkers in clinical trials.
Contralesional Brain Activity in Acute Ischemic Stroke
Authors: Van Kaam Ruud C. , van Putten Michel J.A.M. , Vermeer Sarah E. , Hofmeijer Jeannette
Published: March 2018

Background: The noninjured, contralateral hemisphere is increasingly acknowledged in the process of recovery from acute ischemic stroke. We estimated the value of conventional electroencephalography (EEG) recordings for identifying contralateral hemisphere involvement in relation to functional recovery. Methods: We analyzed 2-min epochs from 21 electrode EEG registrations of 18 patients with acute hemispheric ischemic stroke and compared with 18 age-matched controls. Outcome was dichotomized as good (modified Rankin Scale [mRS] 0–2) or poor (mRS 3–5 or death) at 3 months. Effects of the infarct on the ipsi-and contralateral hemispheres were analyzed by the delta/alpha ratio (DAR) and 2 measures of functional connectivity (magnitude squared coherence [MSC] and weighted phase lag index [WPLI]). Results: DAR was higher in patients than in controls, both in the ipsilateral and in the contralateral hemisphere (median 4.5 ± 6.7 ipsilateral and 2.4 ± 2.0 contralateral vs. 0.5 ± 0.5 in the control group, p < 0.001), indicating robust EEG changes in both lesioned and non-lesioned hemisphere. MSC and WPLI in the alpha and beta frequency bands were lower in patients than in controls in both hemispheres, indicating clear disturbances of functional connectivity (p < 0.05). In the poor outcome group, contralateral MSC and WPLI were lower than in the good outcome group, although these differences did not reach statistical significance. Conclusions: Short conventional EEG measurements show robust changes of brain activity and functional connectivity in both ipsilateral and contralateral hemispheres of patients with acute ischemic stroke. Changes of remote functional connectivity tend to interact with functional recovery. Future studies should estimate predictive values for individual patients and interactions with plasticity enhancing treatments.
Changes in the Proteomic Profile of Acquired Enamel Pellicles as a Function of Their Time of Formation and Hydrochloric Acid Exposure
Authors: Taira Even A. , Ventura Talita M.S. , Cassiano Luiza P.S. , Silva Cintia M.S. , Martini Tatiana , Leite Aline L. , Rios Daniela , Magalhães Ana Carolina , Buzalaf Marília Afonso Rabelo
Published: March 2018

Objective: Changes in the protein profile of acquired enamel pellicles (AEP) formed in vivo over different time periods were evaluated after the application of hydrochloric acid (HCl). Methods: Nine subjects were submitted to dental prophylaxis with pumice. After 3 or 120 min, the teeth were isolated with cotton rolls and 50 μL of 0.1 M HCl (pH 1.0), 0.01 M HCl (pH 2.0), or deionized water were applied on the buccal surface of the teeth for 10 s. The AEP was then collected using an electrode filter paper presoaked in 3% citric acid. After protein extraction, the samples were submitted to reverse-phase liquid chromatography coupled to mass spectrometry (nano LC-ESI-MS/MS). Label-free quantification was performed (Protein Lynx Global Service software). Results: A total of 180 proteins were successfully identified in the AEP samples. The number of identified proteins increased with the time of pellicle formation. Only 4 proteins were present in all the groups (isoforms of IgA, serum albumin, and statherin). The greatest number of proteins identified uniquely in one of the groups was obtained for the groups treated with HCl after 2 h of pellicle formation (approx. 50 proteins). Conclusion: Proteins resistant to removal by HCl, such as serum albumin and statherin, were identified even in the short-term AEP. In addition, 120-min pellicles present many proteins that are resistant to removal by HCl. This suggests an increase in protection against intrinsic acids with the time of pellicle formation, which should be evaluated in future studies.