bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exosomes derived from gemcitabine-resistant cells transfer malignant phenotypic traits via delivery of miRNA-222-3p
Authors: Wei Feng , Ma Chengyuan , Zhou Tong , Dong Xuechao , Luo Qinghua , Geng Li , Ding Lijuan , Zhang Yandong , Zhang Li , Li Nan , Li Yang , Liu Yan 
Published: July 2017

Abstract
Background
Although gemcitabine-based chemotherapy has been established as a core multimodal therapy for non-small cell lung cancer (NSCLC) treatment, its clinical efficacy remains limited by the development of acquired resistance following tumor metastasis and relapse. In this study, we investigated how gemcitabine-resistant (GR) cells contribute to the development of NSCLC tumor malignancy via exosome-mediated transfer of microRNAs.

Methods
We first studied the mechanism of exosome internalization via PKH-67 staining and an immunofluorescence assay, then confirmed our finding by transmission electron microscopy and western blot analysis. Candidate miRNAs were identified through microarray analysis. Thereafter, RT-PCR, MTS, Transwell and soft agar assays were performed to assess the role of exosomic miR-222-3p in vitro. A 3’ untranslated region reporter assay was applied to identify the target of miR-222-3p. A lung metastasis mouse model was constructed to evaluate tumor growth and metastasis in vivo. Finally, clinical samples were used for correlation analysis between exosomic miR-222-3p levels and patients’ response to gemcitabine.

Results
A549-GR–derived exosomes were internalized by receipt cells via caveolin- and lipid raft-dependent endocytosis, which allowed the transfer of miR-222-3p. Exosomic miR-222-3p enhanced the proliferation, gemcitabine resistance, migration, invasion, and anti-anoikis of parental sensitive cells by directly targeting the promoter of SOCS3. In addition, a higher level of exosomic miR-222-3p in sera usually predicted worse prognosis in NSCLC patients.

Conclusion
Our data demonstrate that exosomic-miR-222-3p functions as a principal regulator of gemcitabine resistance and malignant characteristics by targeting SOCS3. The exosomic miR-222-3p level in sera may be a potential prognostic biomarker for predicting gemcitabine sensitivity in NSCLC patients.
Increase in body weight over a two‐year period is associated with an increase in midfoot pressure and foot pain
Authors: Walsh Tom P. , Butterworth Paul A. , Urquhart Donna M. , Cicuttini Flavia M. , Landorf Karl B. , Wluka Anita E. , Michael Shanahan E. , Menz Hylton B. 
Published: July 2017

AbstractBackgroundThere is a well‐recognised relationship between body weight, plantar pressures and foot pain, but the temporal association between these factors is unknown. The aim of this study was to investigate the relationships between increasing weight, plantar pressures and foot pain over a two‐year period.MethodsFifty‐one participants (33 women and 18 men) completed the two‐year longitudinal cohort study. The sample had a mean (standard deviation (SD)) age of 52.6 (8.5) years. At baseline and follow‐up, participants completed the Manchester Foot Pain and Disability Index questionnaire, and underwent anthropometric measures, including body weight, body mass index, and dynamic plantar pressures. Within‐group analyses examined differences in body weight, foot pain and plantar pressures between baseline and follow up, and multivariate regression analysis examined associations between change in body weight, foot pain and plantar pressure. Path analysis assessed the total impact of both the direct and indirect effects of change in body weight on plantar pressure and pain variables.ResultsMean (SD) body weight increased from 80.3 (19.3), to 82.3 (20.6) kg, p = 0.016 from baseline to follow up. The change in body weight ranged from −16.1 to 12.7 kg. The heel was the only site to exhibit increased peak plantar pressures between baseline and follow up. After adjustment for age, gender and change in contact time (where appropriate), there were significant associations between: (i) change in body weight and changes in midfoot plantar pressure (B = 4.648, p = 0.038) and functional limitation (B = 0.409, p = 0.010), (ii) plantar pressure change in the heel and both functional limitation (B = 4.054, p = 0.013) and pain intensity (B = 1.831, p = 0.006), (iii) plantar pressure change in the midfoot and both functional limitation (B = 4.505, p = 0.018) and pain intensity (B = 1.913, p = 0.015). Path analysis indicated that the effect of increasing body weight on foot‐related functional limitation and foot pain intensity may be mediated by increased plantar pressure in the midfoot.ConclusionsThese findings suggest that as body weight and plantar pressure increase, foot pain increases, and that the midfoot may be the most vulnerable site for pressure‐related pain.
Genome-wide DNA methylation profile analysis identifies differentially methylated loci associated with ankylosis spondylitis
Authors: Hao Jingcan , Liu Yang , Xu Jiawen , Wang Wenyu , Wen Yan , He Awen , Fan Qianrui , Guo Xiong , Zhang Feng 
Published: July 2017

Abstract
Background
Ankylosing spondylitis (AS) is a chronic rheumatic and autoimmune disease. Little is known about the potential role of DNA methylation in the pathogenesis of AS. This study was undertaken to explore the potential role of DNA methylation in the genetic mechanism of AS.

Methods
In this study, we compared the genome-wide DNA methylation profiles of peripheral blood mononuclear cells (PBMCs) between five AS patients and five healthy subjects, using the Illumina Infinium HumanMethylation450 BeadChip. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) was performed to validate the relevance of the identified differentially methylated genes for AS, using another independent sample of five AS patients and five healthy subjects.

Results
Compared with healthy controls, we detected 1915 differentially methylated CpG sites mapped to 1214 genes. The HLA-DQB1 gene achieved the most significant signal (cg14323910, adjusted P = 1.84 × 10–6, β difference = 0.5634) for AS. Additionally, the CpG site cg04777551 of HLA-DQB1 presented a suggestive association with AS (adjusted P = 1.46 × 10–3, β difference = 0.3594). qRT-PCR observed that the mRNA expression level of HLA-DQB1 in AS PBMCs was significantly lower than that in healthy control PBMCs (ratio = 0.48 ± 0.10, P < 0.001). Gene Ontology (GO) and KEGG pathway enrichment analysis of differentially methylated genes identified four GO terms and 10 pathways for AS, functionally related to antigen dynamics and function.

Conclusions
Our results demonstrated the altered DNA methylation profile of AS and implicated HLA-DQB1 in the development of AS.
Lenalidomide Maintenance After Autologous Stem-Cell Transplantation in Newly Diagnosed Multiple Myeloma: A Meta-Analysis
Authors: McCarthy Philip L. , Holstein Sarah A. , Petrucci Maria Teresa , Richardson Paul G. , Hulin Cyrille , Tosi Patrizia , Bringhen Sara , Musto Pellegrino , Anderson Kenneth C. , Caillot Denis , Gay Francesca , Moreau Philippe , Marit Gerald , Jung Sin-Ho , Yu Zhinuan , Winograd Benjamin , Knight Robert D. , Palumbo Antonio , Attal Michel 
Published: July 2017

Purpose Lenalidomide maintenance therapy after autologous stem-cell transplantation (ASCT) demonstrated prolonged progression-free survival (PFS) versus placebo or observation in several randomized controlled trials (RCTs) of patients with newly diagnosed multiple myeloma (NDMM). All studies had PFS as the primary end point, and none were powered for overall survival (OS) as a primary end point. Thus, a meta-analysis was conducted to better understand the impact of lenalidomide maintenance in this setting. Patients and Methods The meta-analysis was conducted using primary-source patient-level data and documentation from three RCTs (Cancer and Leukemia Group B 100104, Gruppo Italiano Malattie Ematologiche dell'Adulto RV-MM-PI-209, and Intergroupe Francophone du Myélome 2005-02) that met the following prespecified inclusion criteria: an RCT in patients with NDMM receiving ASCT followed by lenalidomide maintenance versus placebo or observation with patient-level data available and achieved database lock for primary efficacy analysis. Results Overall, 1,208 patients were included in the meta-analysis (605 patients in the lenalidomide maintenance group and 603 in the placebo or observation group). The median PFS was 52.8 months for the lenalidomide group and 23.5 months for the placebo or observation group (hazard ratio, 0.48; 95% CI, 0.41 to 0.55). At a median follow-up time of 79.5 months for all surviving patients, the median OS had not been reached for the lenalidomide maintenance group, whereas it was 86.0 months for the placebo or observation group (hazard ratio, 0.75; 95% CI, 0.63 to 0.90; P = .001). The cumulative incidence rate of a second primary malignancy before disease progression was higher with lenalidomide maintenance versus placebo or observation, whereas the cumulative incidence rates of progression, death, or death as a result of myeloma were all higher with placebo or observation versus lenalidomide maintenance. Conclusion This meta-analysis demonstrates a significant OS benefit and confirms the PFS benefit with lenalidomide maintenance after ASCT in patients with NDMM when compared with placebo or observation.
ΜΟΝΤΕΛΟΠΟΙΩΝΤΑΣ ΠΡΟΒΛΗΜΑΤΑ ΣΤΑΤΙΣΤΙΚΟΥ ΣΥΛΛΟΓΙΣΜΟΥ
Authors: ΠΑΠΑΡΙΣΤΟΔΗΜΟΥ ΕΦΗ , ΜΕΛΕΤΙΟΥ- ΜΑΥΡΟΘΕΣΗ ΜΑΡΙΑ , SERRADO BAYES ANNA 
Published: July 2017

Η συμβολή της μοντελοποίησης μέσω της αξιοποίησης δυναμικών στατιστικών πακέτων για την καλύτερη κατανόηση των στατιστικών εννοιών και την εκτίμηση της πρακτικής τους αξίας κρίνεται ως ιδιαίτερα σημαντική στη σύγχρονη βιβλιογραφία (π.χ., Gil & Ben-Zvi, 2011). Η εργασία εστιάζει στο πώς οι εκπαιδευτικοί ως μεταπτυχιακοί φοιτητές1 μοντελοποιούν προβλήματα στατιστικού συλλογισμού και παρουσιάζει τα αποτελέσματα έρευνας, η οποία πραγματοποιήθηκε στο πλαίσιο μεταπτυχιακού μαθήματος ποσοτικών προσεγγίσεων απευθυνόμενου σε υποψήφιους και εν ενεργεία εκπαιδευτικούς. Τα ευρήματα της έρευνας καταδεικνύουν ότι η άτυπη προσέγγιση της στατιστικής συμπερασματολογίας που υιοθετήθηκε στο μάθημα, η οποία επικεντρώθηκε στην μοντελοποίηση και προσομοίωση μέσω της χρήσης του λογισμικού δυναμικής στατιστικής TinkerPlots2®, συνέβαλε στην ανάπτυξη τόσο της στατιστικής συλλογιστικής των φοιτητών, όσο και του βαθμού εκτίμησης της πρακτικής αξίας της μοντελοποίησης στη διαδικασία λήψης αποφάσεων. Η δυνατότητα που προσφέρει το τεχνολογικό εργαλείο για την κατασκευή μοντέλων και στη συνέχεια την προσομοίωσή τους με σκοπό την επίλυση ρεαλιστικών προβλημάτων, βοήθησε τους φοιτητές-εκπαιδευτικούς να κατανοήσουν τη σχέση του μέρους και του όλου στα δεδομένα τους, την επίδραση του Νόμου των Μεγάλων Αριθμών και τη σύνδεση της θεωρητικής με την εμπειρική πιθανότητα.
Pharmaceutical Product Recalls: Category Effects and Competitor Response
Authors: Bala Ram , Bhardwaj Pradeep , Chintagunta Pradeep K. 
Published: July 2017

In the pharmaceutical industry, a product recall financially impacts not only the firm undertaking the recall but also other competitors in the category since it affects physician and consumer perception of the category as a whole. Often, such competitors have to engage in defensive marketing at the category level without complete certainty about whether a recall will occur or not. Such defensive effort could then lead to a change in postrecall sales effort directed at capturing market share in that category. This decision is affected by the probability of the recall and the size of the loyal segment in the category facing the recall, i.e., physicians who will continue to prescribe the category even without marketing effort. We focus on competitor reaction to product recalls where the competitor participates in multiple product categories that exhibit (dis)economies of scope in sales effort across them. Equilibrium analysis of our game-theoretic model uncovers several managerial insights that illustrate the importance of scale (dis)economies on the competitor’s promotional strategy in the wake of a recall. First, economies of scope across the two products leads to either an increase or decrease in postrecall sales effort for both products simultaneously depending on the loyal market size for the category. Second, diseconomies of scope can lead to a complete withdrawal of postrecall sales effort from one of the two products depending on the size of the loyal market, the cross-category price, and the recall probability. Third, as the recall probability increases, category-defense effort and postrecall sales effort are unequivocally complementary given economies of scope across the two products but may be substitutes given diseconomies of scope. The online appendix is available at https://doi.org/10.1287/mksc.2017.1054 .
Learning to let go: Phenomenologically exploring the experience of a grip and release in salsa dance and everyday life
Authors: Lloyd Rebecca J. 
Published: July 2017

Abstract
Within the context of salsa dance, an exemplar that is highly attuned to gestural communication, there are moments when a perceptual merge, what Csikszentmihalyi posits as flow, is experienced. Movements are not anticipated, rather the fullness of the moment ripples out in fluid responsiveness to miniscule pressures and undulations in the simplest of gestures. Yet, achieving such a flow of reciprocity is not easy, as one must move not from a cognitive place of intention, but rather from a somatic sensibility premised on a corporeal openness. This enquiry thus explores what it is like to let go of habitual tensions that stand in the way of gestural communication within the context of salsa dance, and in so doing, the depth of connection to which attention is drawn represents the intertwining capabilities of relationships between bodies in any relational merge. And in delving into the nuances of gestural fluid responsiveness as guided by Daniel Stern’s notion of emotive motility living within the present moment, we may explore what it is like to form and feel a perceptual connection and the meaning that such moments hold, particularly for those who wish to heal and transform their daily relational existence.
The importance of biochemical and genetic findings in the diagnosis of atypical Norrie disease
Authors: Rodríguez-Muñoz Ana , García-García Gema , Menor Francisco , Millán José M. , Tomás-Vila Miguel , Jaijo Teresa 
Published: July 2017

Abstract

Background:
Norrie disease (ND) is a rare X-linked disorder characterized by bilateral congenital blindness. ND is caused by a mutation in the Norrie disease pseudoglioma (NDP) gene, which encodes a 133-amino acid protein called norrin. Intragenic deletions including NDP and adjacent genes have been identified in ND patients with a more severe neurologic phenotype. We report the biochemical, molecular, clinical and radiological features of two unrelated affected males with a deletion including NDP and MAO genes.

Methods:
Biochemical and genetic analyses were performed to understand the atypical phenotype and radiological findings. Biogenic amines in cerebrospinal fluid (CSF) were measured by high-performance liquid chromatography. The coding exons of NDP gene were amplified by polymerase chain reaction. Multiplex ligation-dependent probe amplification and chromosomal microarray were carried out on both affected males. Computed tomography and magnetic resonance imaging were performed on the two patients.

Results:
In one patient, the serotonin and catecholamine metabolite levels in CSF were virtually undetectable. In both patients, genetic studies revealed microdeletions in the Xp11.3 region, involving the NDP, MAOA and MAOB genes. Radiological examination demonstrated brain and cerebellar atrophy.

Conclusions:
We suggest that alterations caused by MAO deficit may remain during the first years of life. Clinical phenotype, biochemical findings and neuroimaging can guide the genetic study in patients with atypical ND and help us to a better understanding of this disease.
Poly(imide-siloxane)s based on hyperbranched polyimides
Authors: Sysel Petr , Patrova Anna , Lanc Marek , Friess Karel 
Published: July 2017

AbstractPoly(imide-siloxane)s differing in their composition were prepared and characterized. The starting polymer (control) was the hyperbranched polyimide based on 4,4′-oxydiphthalic anhydride and 4,4′,4″-triaminotriphenylmethane. In the poly(imide-siloxane)s, 10 or 40–50 mol% of the 4,4′,4″-triaminotriphenylmethane was theoretically substituted for by amine-terminated siloxane dimer or oligomers. 1,3-Bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane, bis(3-aminopropyl)-terminated poly(dimethylsiloxane) with a theoretical number-average molar mass of 1000 g·mol−1 and bis(3-aminopropyl)-terminated poly(dimethylsiloxane) with a theoretical number-average molar mass of 2500 g·mol−1 were used for this purpose. The thermo-mechanical properties and gas separation characteristics for hydrogen, carbon dioxide and methane of these polymeric products were shown to be dependent on their composition.
Kallistatin: double-edged role in angiogenesis, apoptosis and oxidative stress
Authors: Chao Julie , Li Pengfei , Chao Lee 
Published: July 2017

AbstractKallistatin, via its two structural elements – an active site and a heparin-binding domain – displays a double-edged function in angiogenesis, apoptosis and oxidative stress. First, kallistatin has both anti-angiogenic and pro-angiogenic effects. Kallistatin treatment attenuates angiogenesis and tumor growth in cancer-bearing mice. Kallistatin via its heparin-binding site inhibits angiogenesis by blocking vascular endothelial growth factor (VEGF)-induced growth, migration and adhesion of endothelial cells. Conversely, kallistatin via the active site promotes neovascularization by stimulating VEGF levels in endothelial progenitor cells. Second, kallistatin inhibits or induces apoptosis depending on cell types. Kallistatin attenuates organ injury and apoptosis in animal models, and its heparin-binding site is essential for blocking tumor necrosis factor (TNF)-α-induced apoptosis in endothelial cells. However, kallistatin via its active site induces apoptosis in breast cancer cells by up-regulating miR-34a and down-regulating miR-21 and miR-203 synthesis. Third, kallistatin can act as an antioxidant or pro-oxidant. Kallistatin treatment inhibits oxidative stress and tissue damage in animal models and cultured cells. Kallistatin via the heparin-binding domain antagonizes TNF-α-induced oxidative stress, whereas its active site is crucial for stimulating antioxidant enzyme expression. In contrast, kallistatin provokes oxidant formation, leading to blood pressure reduction and bacterial killing. Kallistatin-mediated vasodilation is partly mediated by H2O2, as the effect is abolished by the antioxidant enzyme catalase. Moreover, kallistatin exerts a bactericidal effect by stimulating superoxide production in neutrophils of mice with microbial infection as well as in cultured immune cells. Thus, kallistatin’s dual roles in angiogenesis, apoptosis and oxidative stress contribute to its beneficial effects in various diseases.
Prevention of renal ischemia/perfusion-induced renal and hepatic injury in adult male Albino rats by oxytocin: role of nitric oxide
Authors: Ragy Merhan Mamdouh , Aziz Neven Makram 
Published: July 2017

Abstract

Background:
Oxytocin (OT) has an anti-inflammatory and antioxidant effect in the different inflammatory models. The current study aimed to evaluate the protective function of OT in renal and hepatic damages triggered by renal ischemia/reperfusion (IR) in rats. Moreover, the effect of NG-nitro-l-arginine methyl ester (l-NAME) was investigated on the kidney and liver functions in renal IR model.

Methods:
Twenty-four rats were divided into four groups (six rats each) as follows: (1) Sham-operated group; (2) Renal IR group; (3) Renal IR+OT group; (4) Renal IR+OT+l-NAME. OT (1 mg/kg, i.p.) was administered 30 min prior to the induced ischemia and was repeated immediately before the reperfusion period. l-NAME (10 mg/kg, i.p.) was given 45 min before IR injury.

Results:
The results revealed that OT significantly attenuated the IR-induced elevations in the serum urea, creatinine, liver transaminases, and TNF-α levels, while nitric oxide (NO) and Bcl-2 levels were significantly increased compared with the IR group. OT also significantly compensated the decrease in the total antioxidant capacities (TAC) and lowered the elevated malondialdehyde (MDA) levels that were observed with renal IR in the renal and hepatic tissues.

Conclusions:
In conclusion, OT ameliorates renal and hepatic damages triggered by renal IR, and this defense involves the suppression of inflammation and apoptosis with regulation of oxidant-antioxidant status. In addition, administration of l-NAME prior to OT partially reversed the protective effect of OT ensuring that one of the protective effects of OT was through the NO production.
Pregnancy outcomes among patients with recurrent pregnancy loss and uterine anatomic abnormalities
Authors: Gabbai Daniel , Harlev Avi , Friger Michael , Steiner Naama , Sergienko Ruslan , Kreinin Andrey , Bashiri Asher 
Published: July 2017

Abstract

Background:
Different etiologies for recurrent pregnancy loss have been identified, among them are: anatomical, endocrine, genetic, chromosomal and thrombophilia pathologies.

Aims:
To assess medical and obstetric characteristics, and pregnancy outcomes, among women with uterine abnormalities and recurrent pregnancy loss (RPL). This study also aims to assess the impact of uterine anatomic surgical correction on pregnancy outcomes.

Methods:
A retrospective case control study of 313 patients with two or more consecutive pregnancy losses followed by a subsequent (index) pregnancy. Anatomic abnormalities were detected in 80 patients. All patients were evaluated and treated in the RPL clinic at Soroka University Medical Center. Out of 80 patients with uterine anatomic abnormalities, 19 underwent surgical correction, 32 did not and 29 had no clear record of surgical intervention, and thus were excluded from this study.

Results:
Women with anatomic abnormalities had a higher rate of previous cesarean section (18.8% vs. 8.6%, P=0.022), tended to have a lower number of previous live births (1.05 vs. 1.37, P=0.07), and a higher rate of preterm delivery (22.9% vs. 10%, P=0.037). Using multivariate logistic regression analysis, anatomic abnormality was identified as an independent risk factor for RPL in patients with previous cesarean section after controlling for place of residence, positive genetic/autoimmune/endocrine workup, and fertility problems (OR 7.22; 95% CI 1.17–44.54, P=0.03). Women suffering from anatomic abnormalities tended to have a higher rate of pregnancy loss compared to those without anatomic abnormalities (40% vs. 30.9%, P=0.2). The difference in pregnancy loss rate among women who underwent surgical correction compared to those who did not was not statistically significant.

Conclusion:
In patients with previous cesarean section, uterine abnormality is an independent risk factor for pregnancy loss. Surgical correction of uterine abnormalities among RPL patients might have the potential to improve live birth rate.