bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lifestyle exercises for bone health and health-related quality of life among premenopausal women: a randomised controlled trial
Authors: Babatunde Opeyemi , Forsyth Jacky 
Published: March 2015

Purpose: Growing evidence supports engagement in physical exercise throughout life for optimal bone health. However, promotion of physical exercise among premenopausal women presents significant challenges, which are yet to be addressed in the design of many bone-health exercise regimes. As a deviation from traditional, facility-based, supervised, long-duration and intense exercise regimes, the efficacy of short-duration, practical, lifestyle physical exercises for improving bone health and quality of life was examined. Methods: Premenopausal women ( N = 96, mean age 22.25 ± 3.5 years; mean BMI 23.43 ± 3.5 kg/m2) participated in a 6-month randomised trial of lifestyle physical exercises for the intervention group and sham exercises for the control group. The participants’ scores on the outcome measure SF-36 was accessed pre- and post-intervention and compared with general population norms according to the SF-36 scoring manual. Paired t-tests were used to examine changes within trial arms from baseline to post-intervention, while analysis of covariance was performed to examine the effect of the lifestyle exercise programme on quality of life of premenopausal women. Results: Compared to 51% at baseline, 63% of the participants were either at or above the general population norm for general health, and the percentage of participants who were below the population health norm for mental health was reduced from 46% at baseline to 38% post-exercise intervention. Comparable improvements in quality of life were found in both trial arms post-participation in the bone-health promotion programme. Conclusions: Bone-health exercises, when implemented as easily adoptable, lifestyle physical activity, may also enhance the quality of life of premenopausal women. Hence, a practical lifestyle approach to exercise may offer a much-needed public health strategy for bone-health promotion among women.
Ankle Impingement Caused by an Intra-articular Plica
Authors: Rosenbaum Andrew J. , Positano Rock G. , Positano Rock C. J. , Dines Joshua S. 
Published: March 2015

Entrapment of soft tissues in the anterolateral gutter of the ankle can cause impingement. When symptomatic, patients complain of chronic ankle pain exacerbated with dorsiflexion. Symptoms of instability and a history of recurring ankle sprains are common findings. Plain radiographs and magnetic resonance imaging may assist clinicians in identifying associated pathology. We present 2 cases of ankle impingement occurring in the setting of equivocal examination and imaging findings. In both cases, arthroscopy revealed a likely congenital, intra-articular plica. Levels of Evidence: Therapeutic, Level IV: Case Study
The Effectiveness of a 6-Week Intervention Program Aimed at Modifying Running Style in Patients With Chronic Exertional Compartment Syndrome
Authors: Helmhout Pieter H. , Diebal Angela R. , van der Kaaden Lisanne , Harts Chris C. , Beutler Anthony , Zimmermann Wes O. 
Published: March 2015

Background: Previous studies have reported on the promising effects of changing running style in patients with chronic exertional compartment syndrome (CECS) using a 6-week training program aimed at adopting a forefoot strike technique. This study expands that work by comparing a 6-week in-house, center-based run training program with a less extensive, supervised, home-based run training program (50% home training). Hypothesis: An alteration in running technique will lead to improvements in CECS complaints and running performance, with the less supervised program producing less dramatic results. Study Design: Cohort study; Level of evidence, 3. Methods: Nineteen patients with CECS were prospectively enrolled. Postrunning intracompartmental pressure (ICP), run performance, and self-reported questionnaires were taken for all patients at baseline and after 6 weeks of running intervention. Questionnaires were also taken from 14 patients (7 center-based, 6 home-based) 4 months posttreatment. Results: Significant improvement between preintervention and postintervention rates was found for running distance (43%), ICP values (36%), and scores on the questionnaires Single Assessment Numeric Evaluation (SANE; 36%), Lower Leg Outcome Survey (LLOS; 18%), and Patient Specific Complaints (PSC; 60%). The mean posttreatment score on the Global Rating of Change (GROC) was between +4 and +5 (“somewhat better” to “moderately better”). In 14 participants (74%), no elevation of pain was reported posttreatment, compared with 3 participants (16%) at baseline; in all these cases, the running test was aborted because of a lack of cardiorespiratory fitness. Self-reported scores continued to improve 4 months after the end of the intervention program, with mean improvement rates of 48% (SANE), 26% (LLOS), and 81% (PSC). The mean GROC score improved to +6 points (“a great deal better”). Conclusion: In 19 patients diagnosed with CECS, a 6-week forefoot running intervention performed in both a center-based and home-based training setting led to decreased postrunning lower leg ICP values, improved running performances, and self-assessed leg condition. The influence of training group was not statistically significant. Overall, this is a promising finding, taking into consideration the significantly reduced investments in time and resources needed for the home-based program.
Downregulation of the Wnt inhibitor CXXC5 predicts a better prognosis in acute myeloid leukemia
Authors: Kühnl Andrea , Valk Peter J. M. , Sanders Mathijs A. , Ivey Adam , Hills Robert K. , Mills Ken I. , Gale Rosemary E. , Kaiser Martin F. , Dillon Richard , Joannides Melanie , Gilkes Amanda , Haferlach Torsten , Schnittger Susanne , Duprez Estelle , Linch David C. , Delwel Ruud , Löwenberg Bob , Baldus Claudia D. , Solomon Ellen , Burnett Alan K. , Grimwade David 
Published: March 2015

Key PointsCXXC5 inhibits Wnt signaling and is a candidate tumor suppressor in AML. Low CXXC5 expression is an independent prognostic factor in AML.
Tumor expression, plasma levels and genetic polymorphisms of the coagulation inhibitor TFPI are associated with clinicopathological parameters and survival in breast cancer, in contrast to the coagulation initiator TF
Authors: Tinholt Mari , Vollan Hans Kristian Moen , Sahlberg Kristine Kleivi , Jernström Sandra , Kaveh Fatemeh , Lingjærde Ole Christian , Kåresen Rolf , Sauer Torill , Kristensen Vessela , Børresen-Dale Anne-Lise , Sandset Per Morten , Iversen Nina 
Published: March 2015

Abstract
Introduction
Hypercoagulability in malignancy increases the risk of thrombosis, but is also involved in cancer progression. Experimental studies suggest that tissue factor (TF) and tissue factor pathway inhibitor (TFPI) are involved in cancer biology as a tumor- promoter and suppressor, respectively, but the clinical significance is less clear. Here, we aimed to investigate the clinical relevance of TF and TFPI genetic and phenotypic diversity in breast cancer.

Methods
The relationship between tumor messenger RNA (mRNA) expression and plasma levels of TF and TFPI (α and β), tagging single nucleotide polymorphisms (tagSNPs) in F3 (TF) (n = 6) and TFPI (n = 18), and clinicopathological characteristics and molecular tumor subtypes were explored in 152 treatment naive breast cancer patients. The effect of tumor expressed TF and TFPIα and TFPIβ on survival was investigated in a merged breast cancer dataset of 1881 patients.

Results
Progesterone receptor negative patients had higher mRNA expression of total TFPI (α + β) (P = 0.021) and TFPIβ (P = 0.014) in tumors. TF mRNA expression was decreased in grade 3 tumors (P = 0.003). In plasma, total TFPI levels were decreased in patients with larger tumors (P = 0.013). SNP haplotypes of TFPI, but not TF, were associated with specific clinicopathological characteristics like tumor size (odds ratio (OR) 3.14, P = 0.004), triple negativity (OR 2.4, P = 0.004), lymph node spread (OR 3.34, P = 0.006), and basal-like (OR 2.3, P = 0.011) and luminal B (OR 3.5, P = 0.005) molecular tumor subtypes. Increased expression levels of TFPIα and TFPIβ in breast tumors were associated with better outcome in all tumor subtypes combined (P = 0.007 and P = 0.005) and in multiple subgroups, including lymph node positive subjects (P = 0.006 and P = 0.034).

Conclusions
This study indicates that genetic and phenotypic variation of both TFPIα and TFPIβ, more than TF, are markers of cancer progression. Together with the previously demonstrated tumor suppressor effects of TFPI, the beneficial effect of tumor expressed TFPI on survival, renders TFPI as a potential anticancer agent, and the clinical significance of TFPI in cancer deserves further investigation.
Site-specific programming of the host epithelial transcriptome by the gut microbiota
Authors: Sommer Felix , Nookaew Intawat , Sommer Nina , Fogelstrand Per , Bäckhed Fredrik 
Published: March 2015

Abstract
Background
The intestinal epithelium separates us from the microbiota but also interacts with it and thus affects host immune status and physiology. Previous studies investigated microbiota-induced responses in the gut using intact tissues or unfractionated epithelial cells, thereby limiting conclusions about regional differences in the epithelium. Here, we sought to investigate microbiota-induced transcriptional responses in specific fractions of intestinal epithelial cells. To this end, we used microarray analysis of laser capture microdissection (LCM)-harvested ileal and colonic tip and crypt epithelial fractions from germ-free and conventionally raised mice and from mice during the time course of colonization.

Results
We found that about 10% of the host’s transcriptome was microbially regulated, mainly including genes annotated with functions in immunity, cell proliferation, and metabolism. The microbial impact on host gene expression was highly site specific, as epithelial responses to the microbiota differed between cell fractions. Specific transcriptional regulators were enriched in each fraction. In general, the gut microbiota induced a more rapid response in the colon than in the ileum.

Conclusions
Our study indicates that the microbiota engage different regulatory networks to alter host gene expression in a particular niche. Understanding host-microbiota interactions on a cellular level may facilitate signaling pathways that contribute to health and disease and thus provide new therapeutic strategies.
Association analyses confirm five susceptibility loci for systemic lupus erythematosus in the Han Chinese population
Authors: Sheng Yu-jun , Xu Jian-hua , Wu Yong-gui , Zuo Xian-bo , Gao Jin-ping , Lin Yan , Zhu Zheng-wei , Wen Lei-lei , Yang Chao , Liu Lu , Cheng Yu-yan , Chang Yan , Yang Lu-lu , Zhou Fu-sheng , Tang Xian-fa , Zheng Xiao-dong , Yin Xian-yong , Tang Hua-yang , Sun Liang-dan , Cui Yong , Yang Sen , Zhang Xue-jun 
Published: March 2015

Abstract
Introduction
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Currently, numerous genetic loci of SLE have been confirmed. Here we try to further explore additional genes contributing to SLE susceptibility in this study.

Methods
Forty nine single nucleotide polymorphisms (SNPs) with moderate-risk for SLE in previous study were genotyped in a large-scale replication study with a total of 3,522 cases and 8,252 controls using the Sequenom Massarray system. Association analyses were performed using logistic regression with gender or sample cohorts as a covariate through PLINK 1.07 software.

Results
This replication effort confirmed five reported SLE susceptibility loci reaching genome-wide levels of significance (P
meta
<5.00 × 10−08): TNFSF4 (rs1418190, odds ratio (OR) = 0.81, Pmeta = 1.08 × 10−08; rs4916219, OR = 0.80, Pmeta = 7.77 × 10−09), IRF8 (rs2934498, OR = 1.25, Pmeta = 4.97 × 10−09), miR-146a (rs2431697, OR = 0.69, Pmeta = 1.15 × 10−22), CD44 (rs2732547, OR = 0.82, Pmeta = 1.55 × 10−11), and TMEM39A (rs12494314, OR = 0.84, Pmeta = 1.01 × 10−09). Further logistic regression analysis indicated that the genetic effects within TNFSF4 detected in this study are independent from our previously reported signals.

Conclusions
This study increases the number of established susceptibility loci for SLE in Han Chinese population and highlights the contribution of multiple variants of modest effect. Although further studies will be required to identify the causal alleles within these loci, the findings make a significant step forward in our understanding of the genetic contribution to SLE in Chinese population.
Nuclear reprogramming with a non-integrating human RNA virus
Authors: Driscoll Christopher B , Tonne Jason M , El Khatib Moustafa , Cattaneo Roberto , Ikeda Yasuhiro , Devaux Patricia 
Published: March 2015

Abstract
Introduction
Advances in the field of stem cells have led to novel avenues for generating induced pluripotent stem cells (iPSCs) from differentiated somatic cells. iPSCs are typically obtained by the introduction of four factors—OCT4, SOX2, KLF4, and cMYC—via integrating vectors. Here, we report the feasibility of a novel reprogramming process based on vectors derived from the non-integrating vaccine strain of measles virus (MV).

Methods
We produced a one-cycle MV vector by substituting the viral attachment protein gene with the green fluorescent protein (GFP) gene. This vector was further engineered to encode for OCT4 in an additional transcription unit.

Results
After verification of OCT4 expression, we assessed the ability of iPSC reprogramming. The reprogramming vector cocktail with the OCT4-expressing MV vector and SOX2-, KLF4-, and cMYC-expressing lentiviral vectors efficiently transduced human skin fibroblasts and formed iPSC colonies. Reverse transcription-polymerase chain reaction and immunostaining confirmed induction of endogenous pluripotency-associated marker genes, such as SSEA-4, TRA-1-60, and Nanog. Pluripotency of derived clones was confirmed by spontaneous differentiation into three germ layers, teratoma formation, and guided differentiation into beating cardiomyocytes.

Conclusions
MV vectors can induce efficient nuclear reprogramming. Given the excellent safety record of MV vaccines and the translational capabilities recently developed to produce MV-based vectors now used for cancer clinical trials, our MV vector system provides an RNA-based, non-integrating gene transfer platform for nuclear reprogramming that is amenable for immediate clinical translation.
Human hepatic stem cells transplanted into a fulminant hepatic failure Alb-TRECK/SCID mouse model exhibit liver reconstitution and drug metabolism capabilities
Authors: Zhang Ran-Ran , Zheng Yun-Wen , Li Bin , Tsuchida Tomonori , Ueno Yasuharu , Nie Yun-Zhong , Taniguchi Hideki 
Published: March 2015

Abstract
Introduction
Chimeric mice with humanized livers were recently established by transplanting human hepatocytes. This mouse model that is repopulated with functional human hepatocytes could be a useful tool for investigating human hepatic cell biology and drug metabolism and for other preclinical applications. Successfully transplanting human hepatocytes into mice requires that recipient mice with liver failure do not reject these human cells and provide a suitable microenvironment (supportive niche) to promote human donor cell expansion and differentiation. To overcome the limitations of current mouse models, we used Alb-TRECK/SCID mice for in vivo human immature hepatocyte differentiation and humanized liver generation.

Methods
1.5 μg/kg diphtheria toxin was administrated into 8-week-old Alb-TRECK/SCID mice, and the degree of liver damage was assessed by serum aspartate aminotransferase activity levels. Forty-eight hours later, mice livers were sampled for histological analyses, and the human donor cells were then transplanted into mice livers on the same day. Chimeric rate and survival rate after cell transplantation was evaluated. Expressions of human hepatic-related genes were detected. A human albumin enzyme-linked immunosorbent assay was performed after 50 days of transplantation. On day 60 after transplantation, drug metabolism was examined in mice.

Results
Both human primary fetal liver cells and hepatic stem cells were successfully repopulated in the livers of Alb-TRECK/SCID mice that developed lethal fulminant hepatic failure after administering diphtheria toxin; the repopulation rate in some mice was nearly 100%. Compared with human primary fetal liver cells, human hepatic stem cell transplantation rescued Alb-TRECK/SCID mice with lethal fulminant hepatic failure, and human hepatic stem cell-derived humanized livers secreted more human albumin into mouse sera and also functioned as a “human liver” that could metabolize the drugs ketoprofen and debrisoquine.

Conclusion
Our model of a humanized liver in Alb-TRECK/SCID mice may provide for functional applications such as drug metabolism, drug to drug interactions, and promote other in vivo and in vitro studies.
Acyclic retinoid induces differentiation and apoptosis of murine hepatic stem cells
Authors: Guan Hong-Bin , Nie Yun-Zhong , Zheng Yun-Wen , Takiguchi Kazuya , Yu Hong-Wei , Zhang Ran-Ran , Li Bin , Tsuchida Tomonori , Taniguchi Hideki 
Published: March 2015

Abstract
Introduction
The therapeutic potential of acyclic retinoid (ACR), a synthetic retinoid, has been confirmed in experimental and clinical studies. Therapeutic targets include precancerous and cancer stem cells. As ACR is also involved in developmental processes, its effect on normal hepatic stem cells (HpSCs) should be investigated for understanding the underlying mechanisms. Here, we examined effects of the acyclic retinoid peretinoin on fresh isolated murine HpSCs.

Methods
We isolated c-kit−CD29+CD49f+/lowCD45−Ter119− cells from murine fetal livers using flow cytometry. To evaluate the effect of ACR, we traced clonal expansion and analyzed cell differentiation as well as apoptosis during the induction process by immunofluorescent staining and marker gene expression.

Results
ACR dose-dependently inhibited HpSCs expansion. Stem cell clonal expansion was markedly inhibited during the culture period. Moreover, ACR showed a significant promotion of HpSC differentiation and induction of cellular apoptosis. The expression of stem cell marker genes, Afp, Cd44, and Dlk, was downregulated, while that of mature hepatocyte genes, Alb and Tat, and apoptosis-related genes, Annexin V and Caspase-3, were upregulated. Flow cytometry showed that the proportion of Annexin V-positive cells increased after ACR incubation compared with the control. Data obtained by immunofluorescent staining for albumin and Caspase-3 corroborated the data on gene expression. Finally, we found that ACR directly regulates the expression of retinoic acid receptors and retinoid X receptors.

Conclusions
These findings indicate that ACR inhibits the clonal expansion of normal HpSCs in vitro and promotes the differentiation of immature cells by regulating receptors of retinoic acid.
The importance of frequency in estimating labour market transition rates
Authors: Gomes Pedro 
Published: March 2015

AbstractLabour market transition rates are typically estimated using survey data, which are mainly carried out at monthly or quarterly frequency. I argue that rates from surveys at different frequencies are not comparable, even if corrected for time aggregation. I estimate labour market transition rates using monthly and quarterly frequency CPS data. I apply a time-aggregation correction to make them comparable. I find notable differences in terms of levels and volatilities. While the continuous time-aggregation correction does not alter the unemployment decomposition using the monthly survey, it does so when using the quarterly survey.Jel codes:E24; J60
Projections of potential flows to the enlarging EU from Ukraine, Croatia and other Eastern neighbors
Authors: Fertig Michael , Kahanec Martin 
Published: March 2015

AbstractThis study evaluates potential migration flows to the European Union from its Eastern neighbors and Croatia. We perform out-of-sample forecasts to time series cross-sectional data about post-enlargement migration flows following the EU’s 2004 enlargement. We consider two baseline policy scenarios, with and without accession of sending countries to the EU. Our results show that migration flows are driven by migration costs and economic conditions, but the largest effects accrue to policy variables. In terms of the predicted flows: (i) we can expect modest migration flows in the case of no liberalization of labor markets and only moderately increased migration flows under liberalization; (ii) after an initial increase following liberalization, migration flows will subside to a long run steady state; (iii) Ukraine will send the most migrants; and (iv) the largest inflows in absolute terms are predicted for Germany, Italy and Austria, whereas Ireland, Denmark, Finland and again Austria are the main receiving countries relative to their population.
Mesh-objective two-scale finite element analysis of damage and failure in ceramic matrix composites
Authors: Meyer Pascal , Waas Anthony M 
Published: March 2015

AbstractA mesh-objective two-scale finite element approach for analyzing damage and failure of fiber-reinforced ceramic matrix composites is presented here. The commercial finite element software suite Abaqus is used to generate macroscopic models, e.g., structural-level components or parts of ceramic matrix composites (CMCs), coupled with a second finite element code which pertains to the sub-scale at the fiber-matrix interface level, which is integrated seamlessly using user-generated subroutines and referred to as the integrated finite element method (IFEM). IFEM calculates the reaction of a microstructural sub-scale model that consists of a representative volume element (RVE) which includes all constituents of the actual material, e.g., fiber, matrix, and fiber/matrix interfaces, details of packing, and nonuniformities in properties. The energy-based crack band theory (CBT) is implemented within IFEM’s sub-scale constitutive laws to predict micro-cracking in all constituents included in the model. The communication between the micro- and macro-scale is achieved through the exchange of strain, stress, and stiffness tensors. Important failure parameters, e.g., crack path and proportional limit, are part of the solution and predicted with a high level of accuracy. Numerical predictions are validated against experimental results.
Estrogens Prevent Metabolic Dysfunctions Induced by Circadian Disruptions in Female Mice
Authors: Zhu Liangru , Zou Fang , Yang Yongjie , Xu Pingwen , Saito Kenji , Othrell Hinton Antentor , Yan Xiaofeng , Ding Hongfang , Wu Qi , Fukuda Makoto , Sun Zheng , Tong Qingchun , Xu Yong 
Published: March 2015

Abstract
Circadian disruption has become a significant factor contributing to the epidemics of obesity and insulin resistance. However, interventions to treat metabolic dysfunctions induced by circadian disruptions are limited. The ovarian hormone, estrogen, produces important antiobesity and antidiabetic effects in female animals and has profound effects on daily behavioral rhythms. Here, we show that in female mice depleted with endogenous estrogens, a jet-lag paradigm induced visceral fat accumulation and systemic insulin resistance, which were associated with altered expression of multiple circadian genes in the visceral fat depot. Interestingly, all these jet-lag-induced deficits were completely rescued in female mice supplemented with exogenous estrogens. We further examined 24-hour oscillations of circadian genes in adipose tissues in female mice with estrogen depletion or replacement and showed that expression levels of the circadian gene, period circadian protein homolog 2, oscillate in visceral adipose tissue in an estrogen-dependent manner. Together, our results indicate that estrogens interact with the intrinsic circadian clock in adipose tissue and prevent abnormal lipid accumulation caused by circadian disruptions.