bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk-Neutral Densities: A Review
Authors: Figlewski Stephen
Published: September 2018

Trading in options with a wide range of exercise prices and a single maturity allows a researcher to extract the market's risk-neutral density (RND) over the underlying price at expiration. The RND contains investors’ beliefs about the true probabilities blended with their risk preferences, both of which are of great interest to academics and practitioners alike. With a particular focus on US equity options, I review the historical development of this powerful concept, practical details of fitting an RND to options market prices, and the many ways in which investigators have tried to distill true expectations and risk premia from observed RNDs. I briefly discuss areas of active current research including the pricing kernel puzzle and the volatility surface, and offer thoughts on what has been learned about RNDs so far and fruitful directions for future research.
The functional role of protease-activated receptors on contractile responses by activation of Ca2+sensitization pathways in simian colonic muscles
Authors: Sung Tae Sik , Lu Hongli , Sung Juno , Yeom Jong Hoon , Perrino Brian A. , Koh Sang Don
Published: September 2018

It has been known that activation of protease-activated receptors (PARs) affects gastrointestinal motility. In this study, we tested the effects of PAR agonists on electrical and contractile responses and Ca2+sensitization pathways in simian colonic muscles. The Simian colonic muscle was initially hyperpolarized by PAR agonists. After the transient hyperpolarization, simian colonic muscle repolarized to the control resting membrane potential (RMP) without a delayed depolarization. Apamin significantly reduced the initial hyperpolarization, suggesting that activation of small conductance Ca2+-activated K+(SK) channels is involved in the initial hyperpolarization. In contractile experiments, PAR agonists caused an initial relaxation followed by an increase in contractions. These delayed contractile responses were not matched with the electrical responses that showed no after depolarization of the RMP. To investigate the possible involvement of Rho-associated protein kinase 2 (ROCK) pathways in the PAR effects, muscle strips were treated with ROCK inhibitors, which significantly reduced the PAR agonist-induced contractions. Furthermore, PAR agonists increased MYPT1 phosphorylation, and ROCK inhibitors completely blocked MYPT1 phosphorylation. PAR agonists alone had no effect on CPI-17 phosphorylation. In the presence of apamin, PAR agonists significantly increased CPI-17 phosphorylation, which was blocked by protein kinase C (PKC) inhibitors suggesting that Ca2+influx is increased by apamin and is activating PKC. In conclusion, these studies show that PAR activators induce biphasic responses in simian colonic muscles. The initial inhibitory responses by PAR agonists are mainly mediated by activation of SK channels and delayed contractile responses are mainly mediated by the CPI-17 and ROCK Ca2+sensitization pathways in simian colonic muscles.

NEW & NOTEWORTHY In the present study, we found that the contractile responses of simian colonic muscles to protease-activated receptor (PAR) agonists are different from the previously reported contractile responses of murine colonic muscles. Ca2+sensitization pathways mediate the contractile responses of simian colonic muscles to PAR agonists without affecting the membrane potential. These findings emphasize novel mechanisms of PAR agonist-induced contractions possibly related to colonic dysmotility in inflammatory bowel disease.
The Hip Morphology Changes with Ageing in Asian Population
Authors: Yin Yingchao , Zhang Ruipeng , Jin Lin , Li Shilun , Hou Zhiyong , Zhang Yingze
Published: September 2018

Objectives. This study aims to determine the changing in hip anatomy parameters with age and reveals the reason for the extorsion of lower extremity in the aged. Design. Retrospective study. Participants. One hundred and forty patients who had received imaging check of the femur and acetabulum between October 2013 and October 2016 were included in this study. Main Outcome Measures. The femoral neck torsion angle (FNTA), neck-shaft angle (NSA), and acetabular anteversion angle (AVA) were measured by an experienced orthopedic surgeon. All the patients’ demographic and physical characteristics including age, sex, body laterality, height, and weight were recorded. The Student t-test, two-way ANOVA, Pearson correlation, and multiple linear regression were used for the statistical analysis. Results. The mean age for male and female was 45.01±15.38 and 49.30±17.63 years, respectively. Outcomes revealed that the NSA on the right side of the body, 133.46±4.46° in male and 134.36±4.71° in female, was statistically higher than the left side. Female FNTA had significantly higher values than male (P<0.01). Two-way ANOVA reveals that FNTA and AVA were correlated with age (P<0.05) but not weight, height, or BMI. NSA was correlated with age, weight, and BMI (P<0.05) but not height. Multiple linear regression analysis showed that only age made an independent contribution to NSA. Conclusions. The NSA and FNTA of Asian population may have an obvious decrease whereas AVA increases with ageing, which reveals the reason for the extorsion of lower extremity with elderly. During hip-related surgery in elderly patients, more attention should be paid to these lower extremity anatomic changes.
Management Strategies and Outcomes for Hyponatremia in Cirrhosis in the Hyponatremia Registry
Authors: Sigal Samuel H. , Amin Alpesh , Chiodo Joseph A. , Sanyal Arun
Published: September 2018

Aim. Treatment practices and effectiveness in cirrhotic patients with hyponatremia (HN) in the HN Registry were assessed. Methods. Characteristics, treatments, and outcomes were compared between patients with HN at admission and during hospitalization. For HN at admission, serum sodium concentration [Na] response was analyzed until correction to > 130 mmol/L, switch to secondary therapy, or discharge or death with sodium ≤ 130 mmol/L. Results. Patients with HN at admission had a lower [Na] and shorter length of stay (LOS) than those who developed HN (P < 0.001). Most common initial treatments were isotonic saline (NS, 36%), fluid restriction (FR, 33%), and no specific therapy (NST, 20%). Baseline [Na] was higher in patients treated with NST, FR, or NS versus hypertonic saline (HS) and tolvaptan (Tol) (P < 0.05). Treatment success occurred in 39%, 39%, 52%, 78%, and 81% of patients with NST, FR, NS, HS, and Tol, respectively. Relapse occurred in 55% after correction and was associated with increased LOS (9 versus 6 days, P < 0.001). 34% admitted with HN were discharged with HN corrected. Conclusions. Treatment approaches for HN were variable and frequently ineffective. Success was greatest with HS and Tol. Relapse of HN is associated with increased LOS.
Red Cell Distribution Width Is Positively Correlated with Atherosclerotic Cardiovascular Disease 10-Year Risk Score, Age, and CRP in Spondyloarthritis with Axial or Peripheral Disease
Authors: Ahmad Hassan , Khan Mariam , Laugle Michelle , Jackson Desmond A. , Burant Christopher , Malemud Charles J. , Askari Ali D. , Mattar Maya , Blumenthal David E. , Zidar David A. , Anthony Donald D.
Published: September 2018

Background. Red blood cell distribution width (RDW) is a routine hematologic parameter that is a predictor of cardiovascular disease (CVD) events and is independent of combined traditional risk factor scoring systems. The RDW has also been associated with rheumatic disease activity. Whether RDW is associated with traditional CVD risk factors or Atherosclerotic Cardiovascular Disease (ASCVD) 10-year CVD risk score in patients with seronegative spondyloarthritis with axial or peripheral disease has not been previously determined.Methods. We performed a retrospective, chart review study evaluating the relationship between RDW, albumin, hemoglobin, C-reactive protein (CRP), absolute lymphocyte count (ALC), and ASCVD scoring parameters [age, hypertension status, diabetes mellitus (DM) status, lipid profile, and smoking status] in a cohort of spondyloarthritis patients, taking into consideration their HLA-B27 status, race, and treatment status.Results. RDW was found to positively correlate with ASCVD 10-year score and age, and ASCVD score did not change over time after patients were treated for spondyloarthritis. Albumin was found to negatively correlate with ASCVD 10-year risk score. Both RDW and albumin correlated with CRP. ALC failed to correlate with ASCVD 10-year score but did show a tendency to be associated with CVD, CVD events, and cardiac conduction abnormalities.Conclusions. These data indicate that further study is warranted to evaluate RDW, albumin level, and ALC as potential predictors of CVD in the spondyloarthritis patient population.
Diagnostic Interpretation Guidance for Pediatric Enteric Pathogens: A Modified Delphi Consensus Process
Authors: Stang Antonia S. , Trudeau Melanie , Vanderkooi Otto G. , Lee Bonita E. , Chui Linda , Pang Xiao-Li , Allen Vanessa , Burnham Carey-Ann D. , Goldfarb David M. , MacDonald Judy , Parsons Brendon , Petrich Astrid , Pollari Frank , Tarr Phillip I. , Tipples Graham , Zhuo Ran , Freedman Stephen B.
Published: September 2018

Background. We sought to develop diagnostic test guidance definitions for pediatric enteric infections to facilitate the interpretation of positive test results in the era of multianalyte molecular diagnostic test platforms.Methods. We employed a systematic, two-phase, modified Delphi consensus process consisting of three web-based surveys and an expert panel face-to-face meeting. In phase 1, we surveyed an advisory panel of North American experts to select pathogens requiring diagnostic test guidance definition development. In phase 2, we convened a 14-member expert panel to develop, refine, and select the final definitions through two web-based questionnaires interspersed with a face-to-face meeting. Both questionnaires asked panelists to rate the degree to which they agreed that if the definition is met the pathogen is likely to be causative of clinical illness.Results. The advisory panel survey identified 19 pathogens requiring definitions. In the expert panel premeeting survey, 13 of the 19 definitions evaluated were rated as being highly likely (“agree” or “strongly agree”) to be responsible for acute gastroenteritis symptoms by ≥67% of respondent panel members. The definitions for the remaining six pathogens (Aeromonas, Clostridium difficile, Edwardsiella,nonenteric adenovirus, astrovirus, andEntamoeba histolytica) were indeterminate. After the expert panel meeting, only two of the modified definitions,C. difficileandE. histolytica/dispar, failed to achieve thea priorispecified threshold of ≥67% agreement.Conclusions.We developed diagnostic test guidance definitions to assist healthcare providers for 17 enteric pathogens. We identified two pathogens that require further research and definition development.
A Bioinformatic Profile of Gene Expression of Colorectal Carcinoma Derived Organoids
Authors: A Peng , Xu Xinyi , Wang Chenglin , Ye Ling , Yang Jing
Published: September 2018

Colorectal carcinoma is one of the common cancers in human. It has been intensely debated whether the in vitro cancer cell lines are closely enough for recapitulating the original tumor in understanding the molecular characteristic of CRC. Organoid as a new in vitro 3D culture system has sprang out in CRC study for the capability in reviving the original tissue. The aim of this study is to profile the gene expression of CRC organoid. The gene expression GSE64392 was from GEO database contained 20-patients-derived 37 organoid samples, including 22 colorectal tumor organoid samples and 15 paired healthy samples. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were applied for classifying differentially expressed genes (DEGs). Protein interaction among DEGs was analyzed by Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape software. In total, 853 gene sequences were identified. GO analysis revealed that DEGs were extensively involved in various biological process (BP), like proliferation, cell cycle, and biosynthesis. KEEG pathway analysis showed that WNT, MAPK, TGF-β, SHH, ECM-receptor interaction, and FGF pathways were altered. DEGs which were identified with protein interactions were major response for extracellular matrix organization and the GPCR pathway. In conclusion, our study profiled the DEGs in CRC organoids and promotes our understanding of the CRC organoids as a new model for colorectal cancer research.
Cell-Free Expression of Unnatural Amino Acid Incorporated Aquaporin SS9 with Improved Separation Performance in Biomimetic Membranes
Authors: Wei Peilian , Zhuang Bingjia , Yu Daoyong , Sharipova Aziza , Cai Jin , Huang Lei , Lian Jiazhang , Xu Zhinan
Published: September 2018

Aquaporins (AQPs) are widely applied in biomimetic membranes for water recycling and desalination. In this study, a novel aquaporin was isolated fromPhotobacterium profundumSS9 (AQP SS9), which showed high water permeability and potential for practical water purification applications. To improve the stability of the AQP SS9 embedded biomimetic membranes, a modified AQP SS9 was obtained by incorporation of an unnatural amino acid (p-propargyloxyphenylalanine,pPpa) (P-AQP SS9)in vitrousing a mutatedMethanocaldococcus jannaschiityrosyl-tRNA synthetase (TyrRS) and the cell-free expression system. The modified AQP SS9 can covalently link with phospholipids and hence significantly improve the stability of biomimetic membranes. The concentration of Mg2+and fusion expression with signal peptides were evaluated to enhance the expression level of P-AQP SS9, resulting in a highest yield of 49 mg/L. The modified AQP SS9 was then reconstituted into DOPC liposomes and analyzed by a stopped-flow spectrophotometer. The obtained water permeability coefficient (Pf) of 7.46×10−4m/s was 5.7 times higher than that of proteoliposomes with the wild-type AQP SS9 (Pf=1.31×10−4m/s) and 12.1 times higher than that of the DOPC liposomes (Pf=6.15×10−5m/s). This study demonstrates the development of a cell-free system for the expression of membrane proteins with much higher stability and the potential application of the modified aquaporins for water filtration.
Clinical Value of Combined Determination of Serum B7-H4 with Carcinoembryonic Antigen, Osteopontin, or Tissue Polypeptide-Specific Antigen for the Diagnosis of Colorectal Cancer
Authors: Wang Peng , Li Chun , Zhang Fan , Ma Xuzhe , Gai Xiaodong
Published: September 2018

Aim. B7-H4 is member of the B7 family that negatively regulates the immune response, which are associated with tumor development and prognosis. The present study is aimed at examining serum B7-H4 expression and exploring its contribution to diagnosis in patients with colorectal cancer.Methods. We determined serum expressions of B7-H4, carcinoembryonic antigen (CEA), osteopontin (OPN), and tissue polypeptide-specific antigen (TPS) in 59 patients with colorectal cancer and 29 healthy volunteers and analyzed the diagnostic value of B7-H4 combined with CEA, OPN, or TPS detection for colorectal cancer. B7-H4, OPN, and TPS serum expressions were measured by enzyme-linked immunosorbent assay, and CEA was measured by electrochemical luminescence detection.Results. Serum B7-H4 levels were significantly higher in colorectal cancer patients compared with paired normal controls (P=0.001). B7-H4 serum level was positively correlated with infiltration depth, tumor masses, and lymph node metastasis (P=0.004,P=0.016, andP=0.0052, respectively). We also detected serum expression of B7-H4 before and after radical resection and showed that B7-H4 levels decreased significantly during the first week postoperation (P=0.0064). We used receiver operating characteristic (ROC) curve analysis to indicate the potential diagnostic values of these markers. The areas under the ROC curves (AUC) for B7-H4, OPN, TPS, and CEA were 0.867, 0.805, 0.812, and 0.833, respectively. The optimal sensitivity and specificity of B7-H4 for discriminating between colon cancer patients and healthy controls were 88.2% and 86.7%, respectively, using a cut-off of value of 78.89 ng/mL. However, combined ROC analysis using B7-H4 and CEA revealed an AUC of 0.929, with a sensitivity of 98.9% and a specificity of 80.4% for discriminating colon cancer patients from healthy controls.Conclusions. B7-H4 was highly expressed in the serum in colorectal cancer patients. Detection of B7-H4 plus CEA showed significantly increased sensitivity and specificity for discriminating between colorectal cancer patients and healthy controls compared to individual detection of these markers. Combined detection of serum B7-H4 and CEA may thus have the potential to become a new laboratory method for the early clinical diagnosis and prognostic evaluation of colorectal cancer.
A New Modified Three-Term Hestenes–Stiefel Conjugate Gradient Method with Sufficient Descent Property and Its Global Convergence
Authors: Baluch Bakhtawar , Salleh Zabidin , Alhawarat Ahmad
Published: September 2018

This paper describes a modified three-term Hestenes–Stiefel (HS) method. The original HS method is the earliest conjugate gradient method. Although the HS method achieves global convergence using an exact line search, this is not guaranteed in the case of an inexact line search. In addition, the HS method does not usually satisfy the descent property. Our modified three-term conjugate gradient method possesses a sufficient descent property regardless of the type of line search and guarantees global convergence using the inexact Wolfe–Powell line search. The numerical efficiency of the modified three-term HS method is checked using 75 standard test functions. It is known that three-term conjugate gradient methods are numerically more efficient than two-term conjugate gradient methods. Importantly, this paper quantifies how much better the three-term performance is compared with two-term methods. Thus, in the numerical results, we compare our new modification with an efficient two-term conjugate gradient method. We also compare our modification with a state-of-the-art three-term HS method. Finally, we conclude that our proposed modification is globally convergent and numerically efficient.
Optimal Power Factor Regulation of Dispersed Wind Farms under Diverse Load and Stochastic Wind Conditions Based on Improved Firefly Algorithm
Authors: Liu Hao , Wang Wei , Cui Jia , Tang Fen
Published: September 2018

Aiming at the instability of voltage and large network loss of dispersed wind farms (DWFs) integration into distribution network (DN), an optimal power factor regulation method based on improved firefly algorithm is proposed. Firstly, the generalized load model based on the static voltage characteristics is analyzed. Then reactive power capabilities of DWFs are thoroughly discussed and the influences of DWFs with variable power factor on network loss and voltage profile are presented. In order to reduce network loss and enhance power quality, optimal power factor regulation of DWFs based on improved firefly algorithm (IFA) is proposed. Finally, results of the benchmark IEEE-33 node system show the feasibilities and validities of the proposed method and the superiorities of proposed IFA are revealed by comparison with the existing algorithms.
Optimizing Testing-Resource Allocation Using Architecture-Based Software Reliability Model
Authors: Okamura Hiroyuki , Dohi Tadashi
Published: September 2018

In the management of software testing, testing-recourse allocation is one of the most important problems due to the tradeoff between development cost and reliability of released software. This paper presents the model-based approach to design the testing-resource allocation. In particular, we employ the architecture-based software reliability model with operational profile to estimate the quantitative software reliability in operation phase and formulate the multiobjective optimization problems with respect to cost, testing effort, and software reliability. In numerical experiment, we investigate the difference of the presented optimization problem from the existing testing-resource allocation model.
Measurement and Analysis of Hydrogen Distribution in Stress Environment Using Vickers Microhardness Technique
Authors: Gu Lei , Wang Jing , Li Xiaoyang , Zeng Yanjun
Published: September 2018

In this paper, the stress distribution field in front of the crack tip was obtained by loading a modified WOL specimen using a bolt. Considering the relationship between microhardness and hydrogen content or internal stress in the metal, a model based on the change of microhardness increment is proposed to describe the trend of hydrogen concentration distribution in the stress environment. The agreement between theoretical model and experimental results is verified by the Vickers microhardness tester. Based on the model, there is a simple additive relationship between the hydrogen‐induced microhardness increment and the stress‐induced microhardness increment. Therefore, the microhardness tester can be employed to evaluate the hydrogen distribution in metals quantitatively. The experimental results demonstrated that the Vickers microhardness method has accurately revealed the hydrogen concentration behavior accurately in a known equibiaxial stress environment. The hydrogen distribution of specimens in the stress environment was analyzed by taking the change of the microhardness increment along the crack propagation direction of specimens as the indicator.
Anticorrosion Performance of LDH Coating Prepared by CO2 Pressurization Method
Authors: Zhang Xiaochen , Jiang Peng , Zhang Chunyan , Buhe Bateer , Liu Bin , Zhao Yang , Zhang Tao , Meng Guozhe , Wang Fuhui
Published: September 2018

Many surface treatment methods are used to improve the corrosion resistance of magnesium alloys. LDH (layered double hydroxides) conversion coatings are currently found in the most environmentally friendly and pollution-free coatings of magnesium alloy. In this study, the CO2 pressurization method was applied to the preparation of LDH coating on magnesium alloy for the first time. The effect of CO2 pressurization on the formation and corrosion resistance of LDH coating on AZ91D alloy was investigated. The hardness and adhesion were significantly higher on LDH coating in the case of CO2 pressurization than it is in atmospheric pressure. The surface and cross-sectional morphologies show that LDH coating is more compact in the case of CO2 pressurization than with atmospheric pressure. The results of the polarization curve, hydrogen evolution, and immersion tests indicate that the corrosion resistance of the LDH coating prepared by the CO2 pressurization method was significantly improved.
Achtsame Massage und Achtsamkeitsschulung (Insightouch®) bei Depressionen, psychosomatischen und Bindungsstörungen
Authors: Stötter Andreas , Harrer Michael E. , Mosgoeller Wilhelm , Endler Peter Christian , Haring Christian
Published: September 2018

Hintergrund: Bindungsstörungen können das Auftreten von Angst und Depression begünstigen, lassen sich aber durch korrigierende emotionale Erfahrungen verändern. Eine Massage - insbesondere wenn beide, Masseur (m/w) und Klient, sich in einem Zustand der Achtsamkeit befinden - kann eine solche korrigierende Erfahrung vermitteln. In der vorliegenden Interventionsstudie wurden die Auswirkungen von Insightouch® - einer Kombination von achtsamkeitsbasierter Massage mit Achtsamkeitsschulung - untersucht. Teilnehmer und Methoden: Wir rekrutierten 36 Personen mit psychischen Beschwerden, geringer Bindungsfähigkeit und geringer Achtsamkeit. In Intervallen von 8 Wochen wurden mittels validierter Fragebögen Parameter wie psychosomatische Symptome (Brief Symptom Inventory), Bindungsqualitäten (Adult Attachment Scale) und Achtsamkeit (Freiburger Achtsamkeitsfragebogen) erhoben. Die Hälfte der Teilnehmer (Gruppe A) startete mit der 8-wöchigen Behandlungsphase; nach weiteren 8 Wochen ohne Behandlung wurde die Nachhaltigkeit der Behandlungswirkung dokumentiert. Die Teilnehmer der Gruppe B starteten mit einer 8-wöchigen Wartephase (Kontrollphase ohne Behandlung), gefolgt von der Behandlungsphase. Ergebnisse: Während sich nach der Kontrollphase keine signifikanten Änderungen zeigten, bewirkte die aktive Behandlung statistisch signifikante Besserungen der 1) Symptomatik, 2) Bindungsdefizite und 3) Achtsamkeit. Nach der 8-wöchigen Nachbeobachtungsphase waren die psychischen und die bindungsbezogenen Symptome weiter verbessert; die behandlungsbedingt erhöhte Fähigkeit zur Achtsamkeit blieb hoch. Schlussfolgerung: Insightouch als primär nonverbale Intervention erhöht die Bindungsfähigkeit, verbessert psychosomatische Symptome und erhöht nachhaltig die Fähigkeit zur Achtsamkeit.
Brain Diffusion Imaging and Tractography to Distinguish Clinical Severity of Human PLP1-Related Disorders
Authors: Sarret Catherine , Lemaire Jean-Jacques , Sontheimer Anna , Coste Jérôme , Savy Nadia , Pereira Bruno , Roche Bastien , Boespflug-Tanguy Odile
Published: September 2018

Aims: We performed quantitative diffusion tensor imaging and brain tractography to distinguish clinical severity in a series of 35 patients with hypomyelinating PLP1-related disorders classified using the Motor Developmental Score according to the best motor function acquired before the age of 5 years and the gross motor function measure (GMFM) at the time of magnetic resonance imaging acquisition. Methods: We calculated fractional anisotropy and diffusivity values in 26 regions of interest and the numbers of fibers and volumes of hemisphere tractograms. Fiber bundles on tractograms were characterized according to 3 criteria: size, direction of main-stream fibers, and connectivity of bundles (extratelencephalic projections, commissural fibers, and intrahemispheric connections). Results: Age-adjusted multivariate analysis in 3 severity groups revealed increased isotropic diffusion in the superior cerebellar peduncle and grey matter in the most severe group, and larger tractogram volumes and increased numbers of fibers in the least severely affected group. Tractogram patterns showed preserved extratelencephalic projections and a main anterior-posterior aspect of intrahemispheric fibers in most patients, whereas interhemispheric connectivity was variable. The most severely affected and intermediate patients had less intrahemispheric connectivity, with a frequent predominant anterior-posterior direction of main-stream fibers. Interpretation: Diffusion tensor imaging and tractographic parameters can operate as biomarkers to distinguish clinical severity in PLP1-related disorders and could improve our understanding of hypomyelinating leukodystrophies.
The Normative Turn in Early Moral Development
Authors: Tomasello Michael
Published: September 2018

The Cooperation Theory of moral development starts from the premise that morality is a special form of cooperation. Before 3 years of age, children help and share with others prosocially, and they collaborate with others in ways that foster a sense of equally deserving partners. But then, at around the age of 3, their social interactions are transformed by an emerging understanding of, and respect for, normative standards. Three-year-olds become capable of making and respecting joint commitments, treating collaborative partners fairly, enforcing social norms, and feeling guilty when they violate any of these. The almost simultaneous emergence of a normative attitude in all of these interactional contexts demands explanation. We suggest a transactional causal model: the maturation of capacities for shared intentionality (adaptations for cultural life) makes possible new forms of cooperative social interaction, and these new forms of cooperative social interaction foster and guide moral development.
Clinical Validation of PITX2 DNA Methylation to Predict Outcome in High-Risk Breast Cancer Patients Treated with Anthracycline-Based Chemotherapy
Authors: Schmitt Manfred , Wilhelm Olaf G. , Noske Aurelia , Schricker Gabriele , Napieralski Rudolph , Vetter Martina , Aubele Michaela , Perkins Jonathan , Lauber Jürgen , Ulm Kurt , Thomssen Christoph , Martens John W.M. , Weichert Wilko , Kiechle Marion
Published: September 2018

Background: Breast cancer patients at high risk for recurrence are treated with anthracycline-based chemotherapy, but not all patients do equally benefit from such a regimen. To further improve therapy decision-making, biomarkers predicting outcome are of high unmet medical need. Methods: The percent DNA methylation ratio (PMR) of the promoter gene coding for the Paired-like homeodomain transcription factor 2 (PITX2) was determined by a validated methylation-specific real-time polymerase chain reaction (PCR) test. The multicenter study was conducted in routinely collected archived formalin-fixed paraffin-embedded (FFPE) tissue from 205 lymph node-positive breast cancer patients treated with adjuvant anthracycline-based chemotherapy. Results: The cut-off for the PITX2 methylation status (PMR = 12) was confirmed in a randomly selected cohort (n = 60) and validated (n = 145) prospectively with disease-free survival (DFS) at the 10-year follow-up. DFS was significantly different between the PMR ≤ 12 versus the PMR > 12 group with a hazard ratio (HR) of 2.74 (p < 0.001) in the validation cohort and also for the patient subgroup treated additionally with endocrine therapy (HR 2.47; p = 0.001). Conclusions: Early-stage lymph node-positive breast cancer patients with low PITX2 methylation do benefit from adjuvant anthracycline-based chemotherapy. Patients with a high PITX2 DNA methylation ratio, approximately 30%, show poor outcome and should thus be considered for alternative chemotherapy regimens.
Role of SIRT2 in Regulation of Stemness of Cancer Stem-Like Cells in Renal Cell Carcinoma
Authors: Wei Ruojing , He Dalin , Zhang Xinshi
Published: September 2018

Background/Aims: Cancer stem cells (CSCs) contribute to tumorgenesis, invasion and metastasis, and are typically resistant to chemotherapy. Recent reports showed that SIRT2 was upregulated in several cancers. However, whether SIRT2 may be a CSC marker in renal cell carcinoma (RCC) is not clear. Methods: The SIRT2 levels in both RCC samples and the corresponding normal kidney samples (NT) were assessed by RT-qPCR and ELISA. The association between SIRT2 levels and patient survival was examined using Bivariate correlation analysis by Spearman’s Rank Correlation Coefficients. The survival of the patients was analyzed using Kaplan-Meier curve. In vitro, 2 RCC cell lines were co-transduced with a lentivirus expressing both a green fluorescent protein and a luciferase reporter under a cytomegalovirus promoter, and another lentivirus expressing a nuclear red fluorescent protein reporter under the control of a SIRT2 promoter for differentiating SIRT2+ vs SIRT2- RCC cells by flow cytometry. The SIRT2+ vs SIRT2- RCC cells were examined for the potential of forming tumor sphere in a tumor sphere formation assay, resistance to fluorouracil-induced apoptosis by CCK-8 assay, and the frequency of forming tumor in vivo after serial adoptive transplantation by bioluminescence. Results: The levels of SIRT2 were higher in RCC samples than NT. The prognosis of RCC patients with high SIRT2 was worse than that of with low SIRT2. Compared to SIRT2- cells, SIRT2+ cells formed more tumor spheres, appeared to be more resistant towards fluorouracil-induced apoptosis, and generated bigger tumors with higher frequency after serial adoptive transplantation. Conclusion: SIRT2 may be highly expressed in the RCC stem-like cells and regulates cancer metastasis. Selective knockout of SIRT2 or elimination of SIRT2+ cells may improve the therapeutic outcome for patients with RCC.
Endothelial Cells Promote Calcification in Aortic Smooth Muscle Cells from Spontaneously Hypertensive Rats
Authors: Meng Fanxing , Zhao Yonggang , Wang Bing , Li Bingwei , Sheng Youming , Liu Mingming , Li Hongwei , Xiu Ruijuan
Published: September 2018

Background/Aims: Vascular calcification and hypertension are intimately linked, and the progression of hypertension is closely correlated with endothelial dysfunction. However, the role of endothelial cells (ECs) in vascular calcification of hypertension remains unclear. Therefore, the present study explored the effects of ECs on calcification of smooth muscle cells (SMCs) from aortas of spontaneously hypertensive rats (SHR). Methods: Aortic ECs and SMCs were isolated from SHR and Wistar rats, respectively. The roles of ECs in the regulation of SMCs calcification were investigated by co-culture and conditioned culture model. Calcium deposition of SMCs was detected by von Kossa staining. Quantization of calcium content in SMCs was determined colorimetrically by the o-cresolphthalein complexone method. Alkaline phosphatase (ALP) activity was measured colorimetrically by p-nitrophenol. The expression levels of MMP-2, MMP-9 and the calcification-promoting proteins were analyzed by Western blot. Results: Calcium deposition, ALP activity and the expression levels of calcification-promoting proteins in SMCs of SHR were significantly higher than that cultured without ECs after 6 days of co-culture with ECs or conditioned culture with the medium of ECs, however, there were no statistical differences between SMCs of Wistar rats. MMP-2 and MMP-9 in co-cultured ECs from SHR were dramatically higher than that cultured without SMCs, nevertheless, there were no statistical differences between ECs from Wistar rats and between SMCs from SHR or Wistar rats. Moreover, SB-3CT, a specific inhibitor of gelatinases, decreased calcium content and the expression levels of calcification-promoting proteins in both co-cultured and conditionally cultured SMCs from SHR. Conclusion: ECs have the ability to promote calcification of aortic SMCs of SHR, and elevated expressions of MMP-2 and MMP-9 in ECs of SHR might facilitate the calcification of SMCs.
NCOA3 Loss Disrupts Molecular Signature of Chondrocytes and Promotes Posttraumatic Osteoarthritis Progression
Authors: Zhang Bing , Li Zhiyong , Wang Wei , Guo Jichao , Kang Shufeng , Liu Shizhao , Li Hongzhu , Wang Dapeng , Qi Xiangbei
Published: September 2018

Background/Aims: Osteoarthritis (OA) is the most common joint disease. Recently, a novel variant near the nuclear receptor coactivator 3 (NCOA3) has been identified in association with greater risk of developing OA. However, how NCOA3 is regulated in chondrocytes and involved in OA pathogenesis remain elusive. Methods: The expression and DNA methylation of NCOA3 in knee OA cartilage and in vitro dedifferentiated chondrocytes with or without rs6094710 SNP were analyzed by qRT-PCR, immunoblotting, methylation-specific PCR and bisulfite sequencing. NCOA3 was depleted by siRNA or shRNA or inhibited by a chemical inhibitor to assess its role in chondrocyte dedifferentiation or OA pathogenesis in posttraumatic OA animal model established by cruciate ligament transection surgery. Results: We found that compared with normal counterparts, samples with rs6094710 SNP failed to upregulate NCOA3. Further evidence associated this phenotype with DNMT1-mediated hypermethylation in gene promoter region. Moreover, we showed that NCOA3 maintained the molecular signature of chondrocytes dedifferentiating in vitro or exposed to IL-1β, nevertheless, NCOA3 appeared dispensable for preventing OA initiation, since NCOA3 loss did not trigger OA in young mice. Instead, NCOA3 loss promoted posttraumatic OA progression, and in parallel, enhanced NF-κB activation. Finally, the promoted posttraumatic OA progression was significantly retarded when administrated with NF-κB pathway inhibitor, suggesting that NCOA3 lose promotes posttraumatic OA at least partially by enhancing NF-κB activation. Conclusion: Thus, our findings indicate a critical role of NCOA3 in chondrocytes, and imply that manipulating NCOA3 might present a potential therapeutic approach to interfere OA progression.
Nicotinamide Phosphoribosyltransferase Inhibitor APO866 Prevents IL-1β-Induced Human Nucleus Pulposus Cell Degeneration via Autophagy
Authors: Shi Changgui , Wu Huiqiao , Du Di , Im Hee-Jeong , Zhang Ying , Hu Bo , Chen Huajiang , Wang Xinwei , Liu Yang , Cao Peng , Tian Ye , Shen Xiaolong , Gao Rui , van Wijnen Andre J , Ye Xiaojian  , Yuan Wen
Published: September 2018

Background/Aims: Intervertebral discs consist of an extracellular matrix (ECM) with a central gelatinous nucleus pulposus (NP) enclosed in an outer layer known as the annulus fibrosus. ECM metabolic disorders result in loss of boundary between the annulus fibrosus and NP, which can lead to intervertebral disc degeneration (IDD). Proinflammatory cytokines, such as interleukin (IL)-1β, mediate the progression of IDD. Nicotinamide phosphoribosyltransferase (Nampt) catalyzes the first step in the biosynthesis of nicotinamide adenine dinucleotide (NAD) and is known to be induced by IL-1β. APO866 is an inhibitor of NAD biosynthesis and is involved in autophagy. LC3 (microtubule-associated protein 1 light chain 3) is a key regulator of autophagy and is used as an indicator of increased autophagy. Herein, we investigate the role of APO866 in regulating autophagy in NP cells and IL-1β mediated NP cell degeneration and apoptosis. Methods: NP cells were extracted from IDD tissues and cultured in DMEM/F12 medium. Nampt was induced by different concentrations of IL-1β (0, 0.5, 1, 5, 10 ng/mL) for 24 h or NP cells were treated with 10 ng/mL IL-1β for 0, 6, 12, 48 h. QRT-PCR and western blots were used to detect Nampt and ECM-related protein expression in NP tissue of patients with IDD and in NP cells. Confocal analysis was used to detect membrane-bound LC3, Aggrecan, and Collagen II. Results: Nampt is expressed in NP tissue at higher levels in severe grades of IDD (Grade IV and V) compared with low grades (Grade II and III). In NP cells, 10 ng/mL IL-1β induced Nampt expression for 48 h, increased expression of the degradative-associated proteins, ADAMTS4/5 and MMP-3/13, and decreased expression of ECM-related proteins, Aggrecan and Collagen II. However, the Nampt inhibitor APO866 blocked IL-1β induction, and the knockdown of Nampt expression increased the expression of ECM proteins that were inhibited by IL-1β. Moreover, evidence provided by the autophagic markers LC3 and Beclin-1 indicated that APO866 induced NP cell autophagy. Furthermore, although APO866 inhibited the downregulated expression of ECM-related proteins by IL-1β, this function was blocked by autophagy inhibitor, 3-methyladenine. Conclusion: APO866 protects NP cells and induces autophagy by inhibiting IL-1β-induced NP cell degeneration and apoptosis, which may have therapeutic potential in IDD.
ОСОБЛИВОСТІ ЗДОРОВ’ЯЗБЕРІГАЮЧОЇ ПОВЕДІНКИ ТА САМООЦІНКИ ЗДОРОВ’Я СТУДЕНТСЬКОЇ МОЛОДІ
Authors: Danilenko G. M. , Letyago H. V. , Avdiievska O. G. , Savelieva L. M. , Matvienko O. V. , Khmilevskaya I. G. , Razynkova N. S.
Published: September 2018

Мета: на прикладі студентів-медиків оцінити особливості здоров’язберігаючої поведінки та самооцінки їх здоров’я.Матеріали і методи. Проведено оцінку здоров’язберігаючої поведінки студентської молоді на основі аналізу 242 анкетних відповідей студентів V–VI курсів, які навчаються за спеціальністю «Медицина». Використано методики: статистично-математичний, аналіз анкетних даних, аналітико-логічний.Результати. Отримані дані вказують на наявність порушень у здоров’ї студентської молоді, незважаючи на високу самооцінку щодо стану свого здоров’я. Дані відхилення розвиваються в результаті низки таких факторів, як академічне навантаження, індивідуальні особливості ставлення до власного здоров’я, самолікування, поведінкові ризики (куріння, алкоголь), нераціональне харчування.Висновки. Проведене дослідження показало, що існує потреба у вдосконаленні існуючих медико-­соціальних заходів щодо збереження здоров’я студентської молоді – потенціалу нашого суспільства.
ТЕНДЕНЦІЇ СТАНУ ЗДОРОВ’Я ДИТЯЧОГО НАСЕЛЕННЯ ТА ДОСТУПНОСТІ МЕДИЧНОЇ ДОПОМОГИ (за даними вибіркового опитування домогосподарств із дітьми)
Authors: Slabkiy G. A. , Dudnyk S. V.
Published: September 2018

Мета: вивчити, проаналізувати та визначити тенденції стану здоров’я дітей та доступності медичної допомоги домогосподарствам із дітьми за результатами вибіркових досліджень протягом 2012–2016 рр.Матеріали і методи. Дослідження проведено на основі даних вибіркових опитувань домогосподарств із дітьми Державної служби статистики України щодо суб’єктивної оцінки стану здоров’я дітей та доступності медичної допомоги домогосподарствам із дітьми за період 2012–2016 рр. Використано методи: аналітичний, статистичний, порівняльний аналіз, системний підхід.Результати. У ході дослідження, за даними суб’єктивної оцінки, визначено тенденції щодо оцінки стану здоров’я дітей, захворюваності та наявності хронічної патології у дітей, доступності медичної допомоги та її видів домогосподарствам із дітьми за період 2012–2016 рр.Висновки. Встановлені тенденції стану здоров’я дитячого населення та незадовільний рівень доступності медичної допомоги вимагають оптимізації системи надання медичних послуг та медико-санітарної допомоги дитячому населенню країни в цілому.
СКІЛЬКИ МАЮТЬ ТА ХОЧУТЬ МАТИ ДІТЕЙ ЖІНКИ ДІТОРОДНОГО ВІКУ В УКРАЇНІ
Authors: Levchenko O. V. , Smirnova V. L. , Holyachenko A. O.
Published: September 2018

Мета: вивчити та проаналізувати народжуваність дітей жінками дітородного віку.Матеріали і методи. Використано дані галузевої статистики щодо народжуваності населення, дані соціологічного опитування жінок Хмельницької області.Результати. Вивчення причин зниження народжуваності дітей в сучасних умовах показує, що цьому сприяють багато таких чинників, як зниження життєвого рівня населення, зумовлене соціально-економічною кризою, трудова еміграція жінок, державні виплати грошової допомоги при народженні дитини та субсидії, які далеко не компенсують витрати на дитину.Висновки. Отримані результати підтвердили те, що при сприятливих соціально-економічних умовах жінки дітородного віку мали б 2,02 дитини пересічно на одну жінку, що відповідало б стаціонарному типу відтворення населення.
ТАКТИКА ВИБОРУ ЛІКУВАЛЬНО-ПРОФІЛАКТИЧНИХ ЗАХОДІВ У ОСІБ ІЗ РІЗНИМИ ПСИХОФІЗІОЛОГІЧНИМИ СТАНАМИ ПРИ ЛІКУВАННІ ЗАХВОРЮВАНЬ ПАРОДОНТА
Authors: Luchynskiy M. A. , Pyasetska L. P.
Published: September 2018

Мета: обґрунтувати вибір лікувально-профілактичних схем лікування захворювань тканин пародонта в осіб молодого віку залежно від психофізіологічного стану організму.Матеріали і методи. У дослідженні взяли участь 48 осіб із запальними захворюваннями тканин пародонта та 52 пацієнти із запально-дистрофічними хворобами цього органа з різним психофізіологічним станом організму, які були поділені на різні лікувальні групи залежно від обраної тактики лікування.Результати. В основних лікувальних групах були застосовані лікувально-профілактичні комплекси, що включали: гігієнічне навчання та виховання; індивідуальний вибір засобів догляду за порожниною рота з урахуванням індексу гігієни Гріна–Вермільйона, інтенсивності ураження тканин пародонта за індексом РМА, та здійснення професійної гігієни порожнини рота. Схема лікування пацієнтів контрольних лікувальних груп була передбачена діючими стандартами лікування захворювань тканин пародонта.Висновки. При лікуванні захворювань пародонта у цих осіб важливим етапом є індивідуальна та диферен­ці­йо­вана розробка і впровадження місцевих та загальних лікувальних заходів з урахуванням клінічного та психо­соматичного станів пацієнтів.
ЛІКАРСЬКА ПОМИЛКА: ІСТОРИЧНИЙ НАРИС
Authors: Franchuk V. V.
Published: September 2018

Випадки судових позовів, пов’язаних із неналежним наданням медичної допомоги, стали помітною проблемою сучасної України.Мета: встановлення особливостей лікарської помилки в різні історичні періоди. Матеріали і методи. Ретроспективно розглянуто різноманітні історичні факти, пов’язані з лікарськими помилками.Результати. Медичні помилки в різні історичні періоди були пов’язані з різним ступенем відповідальності лікарів. Зародки державного регулювання медичної діяльності спостерігались ще в Стародавньому Римі. В еру раннього християнства неналежне лікарювання було підставою для суворої відповідальності лікаря.Висновки. Проблема професійних помилок супроводжувала медицину з часів її зародження.
REPRINT Detection of Chronic Kidney Disease in Patients With or at Increased Risk of Cardiovascular Disease
Authors: Brosius Frank C. , Hostetter Thomas H. , Kelepouris Ellie , Mitsnefes Mark M. , Moe Sharon M. , Moore Michael A. , Pennathur Subramaniam , Smith Grace L. , Wilson Peter W.F.
Published: September 2018

Chronic kidney disease (CKD) occurs commonly in patients with cardiovascular disease. In addition, CKD is a risk factor for the development and progression of cardiovascular disease. In this advisory, we present recommendations for the detection of CKD in patients with cardiovascular disease. CKD can be reliably detected with the combined use of the Modification of Diet in Renal Disease equation to estimate glomerular filtration rate and a sensitive test to detect microalbuminuria. All patients with cardiovascular disease should be screened for evidence of kidney disease with these two determinations.
Farnesoid X Receptor Activation by Obeticholic Acid Elevates Liver Low-Density Lipoprotein Receptor Expression by mRNA Stabilization and Reduces Plasma Low-Density Lipoprotein Cholesterol in Mice
Authors: Singh Amar Bahadur , Dong Bin , Kraemer Fredric B. , Xu Yanyong , Zhang Yanqiao , Liu Jingwen
Published: September 2018

Objective—

The objective of this study was to determine whether and how activation of farnesoid X receptor (FXR) by obeticholic acid (OCA), a clinical FXR agonist, modulates liver low-density lipoprotein receptor (LDLR) expression under normolipidemic conditions.

Approach and Results—

Administration of OCA to chow-fed mice increased mRNA and protein levels of LDLR in the liver without affecting the sterol-regulatory element binding protein pathway. Profiling of known LDLR mRNA-binding proteins demonstrated that OCA treatment did not affect expressions of mRNA degradation factors hnRNPD (heterogeneous nuclear ribonucleoprotein D) or ZFP36L1 but increased the expression of Hu antigen R (HuR) an mRNA-stabilizing factor. Furthermore, inducing effects of OCA on LDLR and HuR expression were ablated in Fxr
−/−
mice. To confirm the post-transcriptional mechanism, we used transgenic mice (albumin-luciferase-untranslated region) that express a human LDLR mRNA 3′ untranslated region luciferase reporter gene in the liver. OCA treatment led to significant rises in hepatic bioluminescence signals, Luc-untranslated region chimeric mRNA levels, and endogenous LDLR protein abundance, which were accompanied by elevations of hepatic HuR mRNA and protein levels in OCA-treated transgenic mice. In vitro studies conducted in human primary hepatocytes and HepG2 cells demonstrated that FXR activation by OCA and other agonists elicited the same inducing effect on LDLR expression as in the liver of normolipidemic mice. Furthermore, depletion of HuR in HepG2 cells by short interfering RNA transfection abolished the inducing effect of OCA on LDLR expression.

Conclusions—

Our study is the first to demonstrate that FXR activation increases LDLR expression in liver tissue by a post-transcriptional regulatory mechanism involving LDLR mRNA-stabilizing factor HuR.