bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arzoxifene for prevention of fractures and invasive breast cancer in postmenopausal women
Authors: Cummings Steven R , McClung Michael , Reginster Jean-Yves , Cox David , Mitlak Bruce , Stock John , Amewou-Atisso Messan , Powles Trevor , Miller Paul , Zanchetta José , Christiansen Claus 
Published: July 2010

Abstract
Arzoxifene is a selective estrogen receptor modulator (SERM) that has been shown to be more potent in preclinical testing than currently available agents. Its effects on clinical outcomes are not known. In a randomized, blinded trial, women aged 60 to 85 years with osteoporosis, defined as a femoral neck or lumbar spine bone mineral density T-score of −2.5 or less or a vertebral fracture, and women with low bone mass, defined as a bone density T-score of −1.0 or less and above −2.5, were assigned to arzoxifene 20 mg or placebo daily. The primary endpoints were new vertebral fracture in those with osteoporosis and invasive breast cancer in the overall population. After 3 years, the cumulative incidence of vertebral fractures in patients with osteoporosis was 2.3% lower in the arzoxifene group than in the placebo group, a 41% relative risk reduction [95% confidence interval (CI) 0.45–0.77, p &lt; .001]. In the overall population, the cumulative incidence of invasive breast cancer over 4 years was reduced by 1.3%, with a 56% relative reduction in risk (hazard ratio = 0.44, 95% CI 0.26–0.76, p &lt; .001); there was no significant decrease in nonvertebral fracture risk. Arzoxifene increased the cumulative incidence of venous thromboembolic events by 0.7%, with a 2.3-fold relative increase (95% CI 1.5–3.7). Like other SERMs, arzoxifene decreased vertebral fractures and invasive breast cancer while the risk of venous thromboembolic events increased. © 2011 American Society for Bone and Mineral Research.
Application of induced pluripotent stem (iPS) cells in periodontal tissue regeneration
Authors: Duan Xuejing , Tu Qisheng , Zhang Jin , Ye Jinhai , Sommer Cesar , Mostoslavsky Gustavo , Kaplan David , Yang Pishan , Chen Jake 
Published: July 2010

AbstractTissue engineering provides a new paradigm for periodontal tissue regeneration in which proper stem cells and effective cellular factors are very important. The objective of this study was, for the first time, to investigate the capabilities and advantages of periodontal tissue regeneration using induced pluripotent stem (iPS) cells and enamel matrix derivatives (EMD). In this study the effect of EMD gel on iPS cells in vitro was first determined, and then tissue engineering technique was performed to repair periodontal defects in three groups: silk scaffold only; silk scaffold + EMD; and silk scaffold + EMD + iPS cells. EMD greatly enhanced the mRNA expression of Runx2 but inhibited the mRNA expression of OC and mineralization nodule formation in vitro. Transplantation of iPS cells showed higher expression levels of OC, Osx, and Runx2 genes, both 12 and 24 days postsurgery. At 24 days postsurgery in the iPS cell group, histological analysis showed much more new alveolar bone and cementum formation with regenerated periodontal ligament between them. The results showed the commitment role that EMD contributes in mesenchymal progenitors to early cells in the osteogenic lineage. iPS cells combined with EMD provide a valuable tool for periodontal tissue engineering, by promoting the formation of new cementum, alveolar bone, and normal periodontal ligament. J. Cell. Physiol. 226: 150–157, 2010. © 2010 Wiley‐Liss, Inc.
Nongenomic signaling pathways triggered by thyroid hormones and their metabolite 3‐iodothyronamine on the cardiovascular system
Authors: Axelband F. , Dias J. , Ferrão F.M. , Einicker‐Lamas M. 
Published: July 2010

AbstractThyroid hormones play a wide range of important physiological activities in almost all organism. As changes in these hormones levels—observed in hypothyroidism and hyperthyroidism—promote serious derangements of the cardiovascular system, it is important to know their mechanisms of action. Although the classic genomic actions which are dependent on interaction with nuclear receptors to modulate cardiac myocytes genes expression, there is growing evidence about T3 and T4‐triggered nongenomic pathways, resulted from their binding to plasma membrane, cytoplasm, or mitocondrial receptors that leads to a rapidly regulation of cardiac functions. Interestingly both actions converge to amplify thyroid hormone effects on cardiovascular system. T3 and T4 nongenomic actions modify inotropic and chronotropic effects, cardiac action potential duration, cardiac growth, and myocyte shape by protein translation through protein kinases‐dependent signaling cascades, which include PKA, PKC, PI3K, and MAPK, and changes on ion channels and pumps activity. In respect to the decreased systemic vascular resistance seen in hyperthyroidism, T3 appears to activate NOS or ATP‐sensitive K+ channels. In addition, a novel biologically active T4‐derived metabolite has been described, 3‐iodothyronamine, T1AM, which also acts through membrane receptors to mediate nongenomic cardiac effects. This metabolite influences the physiological manifestations of thyroid hormone actions by inducing opposite effects from those stimulated by T3 and T4, such as negative inotropic and chronotropic effects. Therefore, beyond genomic and nongenomic effects of thyroid hormones, it is crucial for there to be an equilibrium between T3 or T4 and T1AM levels for maintaining cardiac homeostasis. J. Cell. Physiol. 226: 21–28, 2010. © 2010 Wiley‐Liss, Inc.
Lapatinib, a dual HER1/HER2 tyrosine kinase inhibitor, augments basal cleavage of HER2 extracellular domain (ECD) to inhibit HER2‐driven cancer cell growth
Authors: Vazquez‐Martin Alejandro , Oliveras‐Ferraros Cristina , Cufí Silvia , Del Barco Sonia , Martin‐Castillo Begoña , Menendez Javier A. 
Published: July 2010

AbstractThe ultimate biological and clinical meaning of shed HER2 extracellular domain (ECD) has remained largely unclear until recently. Oversecretion of soluble HER2 ECD has been shown to inhibit growth of HER2‐overexpressing cancer cells by promoting HER2 ECD dimerization with HER transmembrane receptors thus impairing their cross‐tyrosine phosphorylation and decreasing their activation status. HER2‐targeted drugs capable to enhance the occurrence of basal HER2 ECD shedding but simultaneously preventing formation of truncated cell membrane‐bound HER2 intracellular fragment, which exhibits an undesirable constitutive kinase activity, might be extremely efficient at managing HER2‐positive cancer disease. The dual HER1/HER2 Tyrosine Kinase inhibitor lapatinib, which works intracellularly and directly targets the TK domain of HER2, drastically augments basal shedding of HER2 ECD to inhibit HER2‐driven cancer cell growth. Lapatinib treatment significantly augments the concentration of the inactive (unphosphorylated) form of HER2 protein at the tumor cell membrane and promotes an exacerbated HER2 ECD shedding to the extracellular milieu of HER2‐overexpressing cancer cells. Exacerbated sensitivity of trastuzumab‐resistant cancer cells, which contain nearly undetectable levels of soluble HER2 ECD when compared with trastuzumab‐sensitive parental cells to lapatinib‐induced cell growth inhibition, takes place when lapatinib treatment fully restores high levels of basal HER2 ECD shedding. The dramatic augmentation of HER2 ECD shedding that occurs upon treatment of with lapatinib is fully suppressed in lapatinib‐refractory HER2‐positive cells. These findings, altogether, may provide crucial insights concerning clinical studies aimed to accurately describe HER2 ECD as a potential predictor of response or resistance to the HER2‐targeted drugs trastuzumab and lapatinib. J. Cell. Physiol. 226: 52–57, 2010. © 2010 Wiley‐Liss, Inc.
Phosphorylation of Ser 21 in Fyn regulates its kinase activity, focal adhesion targeting, and is required for cell migration
Authors: Yeo Myeong Gu , Oh Hye Jin , Cho Hong‐Suk , Chun Jang Soo , Marcantonio Eugene E. , Song Woo Keun 
Published: July 2010

AbstractThe tyrosine kinase Fyn is a member of the Src family kinases which are important in many integrin‐mediated cellular processes including cell adhesion and migration. Fyn has multiple phosphorylation sites which can affect its kinase activity. Among these phosphorylation sites, the serine 21 (S21) residue of Fyn is a protein kinase A (PKA) recognition site within an RxxS motif of the amino terminal SH4 domain of Fyn. In addition, S21 is critical for Fyn kinase‐linked cellular signaling. Mutation of S21A blocks PKA phosphorylation of Fyn and alters its tyrosine kinase activity. Expression of Fyn S21A in cells lacking Src family kinases (SYF cell) led to decreased tyrosine phosphorylation of focal adhesion kinase resulting in reduced focal adhesion targeting, which slowed lamellipodia dynamics and thus cell migration. These changes in cell motility were reflected by the fact that cells expressing Fyn S21A were severely deficient in their ability to assemble and disassemble focal adhesions. Taken together, our findings indicate that phosphorylation of S21 within the pPKA recognition site (RxxS motif) of Fyn regulates its tyrosine kinase activity and controls focal adhesion targeting, and that this residue of Fyn is critical for transduction of signals arising from cell‐extracellular matrix interactions. J. Cell. Physiol. 226: 236–247, 2010. © 2010 Wiley‐Liss, Inc.
Species‐specific differences in nitrogen uptake and utilization by six European tree species
Authors: Schulz Horst , Härtling Sigrid , Stange Claus F. 
Published: July 2010

AbstractSpecies‐specific uptake and allocation mechanisms for N are scarce, in particular when trees are cultivated in potted soil under more natural conditions than in hydroponic culture. The objective of this study was to compare specific N‐uptake rates for economically and ecologically important tree species in Central European forests: pine (Pinus sylvestris), spruce (Picea abies), oak (Quercus petraea), beech (Fagus sylvatica), lime (Tilia cordata), and ash (Fraxinus excelsior) when they grow in mineral soil from an old fallow site with a pH of 6. We used an 15N‐labeling method to measure tree seedling 15N uptake in potted soils (Humic Cambisol) when both N forms NH$ _4^+ $ and NO$ _3^- $ were simultaneously present in the soil solution for interspecies comparison and assessment of relationships between specific 15N‐uptake rates and amino acid–accumulation rates or relative growth rates (RGR). The results demonstrate that tree species varied significantly in their capacity to take up NH$ _4^+ $ or NO$ _3^- $ into roots, stems, or leaves, but indicate only marginal differences in their preference for NH$ _4^+ $ or NO$ _3^- $ when they grow in mineral soil. The ranking of specific 15N‐uptake rates for NH$ _4^+ $ and NO$ _3^- $ was oak < beech < spruce < pine < lime < ash. Fine roots of all species had the highest specific 15N‐uptake rates for both N forms, followed by total roots, leaves/needles, and stems. As regards tree seedling species, we found negative relationships between glutamine (Gln)‐accumulation rates in leaves/needles and total 15N‐uptake rates in fine roots. Noteworthy was the fact that, at high Gln‐accumulation rates, the N‐uptake system in fine roots of ash was probably lower under feedback inhibition by the amino acid.
Simultaneous determination of melamine and related compounds by hydrophilic interaction liquid chromatography–electrospray mass spectrometry
Authors: Xia Jingen , Zhou Naiyuan , Zhou Cong , Chen Bo , Wu Yongning , Yao Shouzhuo 
Published: July 2010

AbstractA hydrophilic interaction liquid chromatography coupled to ESI‐MS (HILIC/ESI‐MS) method for the simultaneous determination of melamine and related compounds, i.e. ammeline, ammelide and cyanuric acid in foods was developed and validated. The separation was accomplished on a Venusil HILIC column with a mobile phase of acetonitrile + 10 mM ammonium formate buffer solution at pH 3.5 (88:12, v/v) under isocratic elution mode. For the detection of the targets, the ESI probe worked in the positive and negative switching mode. For each compound, three ions were selected as qualitative ions to obtain high specificity, and the most abundant ion of each compound was selected for quantification to obtain high sensitivity. The target compounds were quantified using SIM with 15N3‐melamine and 13C3‐cyanuric acid being used as an internal standards in the positive and negative modes, respectively. Compared with RP separation mode, HILIC has merits such as high separation and anti‐interference efficiency. The method validation including linearity, LOD, LOQ, precision and recovery proved that the method has merits such high sensitivity, specificity and simplicity versus the other methods reported in the literature.
Evaluation of an on‐capillary copper complexation methodology for the investigation ofin vitrometabolism of dynorphin A 1–17
Authors: Kuhnline Courtney D. , Lunte Susan M. 
Published: July 2010

AbstractDynorphin A 1–17 is an endogenous neuropeptide implicated in a variety of neurological disorders including Alzheimer's and Parkinson's diseases and neuropathic pain. Metabolites of this peptide can exhibit their own unique effectsin vivo, and it is possible that one of these metabolites is responsible for the neurotoxicity. In this article, the use of CE for the separation of dynorphin A 1–17 from four of its metabolites is described. Buffer additives were investigated to eliminate peptide adsorption to the capillary wall and to improve resolution between closely related metabolites. On‐capillary copper complexation was employed and was shown to improve separation efficiency as compared with the separation of native peptides. The method was then applied toin vitrodynorphin metabolism in human plasma as well as rat brain and rat spinal cord slices.
Hepatocellular carcinoma: Ablate and wait versus rapid transplantation
Authors: Roberts John P. , Venook Alan , Kerlan Robert , Yao Francis 
Published: July 2010

Abstract
This opinion piece explores an “ablate and wait” strategy for improving the 5-year recurrence-free outcome of liver transplantation in patients with hepatocellular carcinoma. The Milan criteria delimit by tumor size and number a population of patients who have good survival after liver transplantation. The University of California San Francisco downstaging experience has shown that patients with a tumor burden outside the Milan criteria who undergo tumor ablation and a period of waiting have outcomes that rival those of patients who undergo transplantation within the Milan criteria because the tumor biology is allowed to become apparent by radiological studies during the waiting period. This experience has led to 2 conclusions: first, expansion beyond the Milan criteria should not occur without therapy directed to the tumor followed by a period of waiting to decrease the risk of recurrence, and second, for tumors within the Milan criteria, the same strategy should be considered. Liver Transpl, 2010. © 2010 AASLD.
Determinants of paraoxonase activity in healthy adults
Authors: Boesch‐Saadatmandi Christine , Rimbach Gerald , Schrader Charlotte , Kofler Bettina M. , Armah Christopher K. , Minihane Anne M. 
Published: July 2010

AbstractScope: Paraoxonase‐1 (PON‐1), associated with HDL, is regarded as anti‐atherogenic, attributed to its ability to hydrolyze oxidized lipids. Here, the impact of PON and apolipoprotein E genotypes, age, alcohol and HDL‐cholesterol (HDL‐C) on PON activity is examined. Methods and results: In total, 104 healthy UK adults participated in the study, with basal (PONA) and stimulated (PONB) PON‐1 activities and arylesterase activity determined in these individuals. In univariate and correlation analysis age, HDL‐C, alcohol intake and both PON genotypes were significantly associated with PONA and PONB activities (p<0.05). However, in the standard linear regression model, which explained 69% of the variability in both PONA (p<0.001) and PONB activities (p<0.001) only PON Q192R genotype emerged as a significant independent determinant, with four to fivefold higher levels in the RR versus wild‐type QQ genotype groups. For PON arylesterase, HDL‐C (p=0.030), apolipoprotein E (p=0.023) and PON Q192R (p=0.002) and PON L55M (p=0.002) genotypes collectively explained 14% of the total variability in the regression model. Conclusion: Our results indicate that PON genotypes are stronger determinants of PON activity relative to the other potential modulators assessed. The relative impact of dietary components on PON activities remains to be established.
Low‐volume resistance exercise attenuates the decline in strength and muscle mass associated with immobilization
Authors: Oates Bryan R. , Glover Elisa I. , West Daniel W. , Fry Jessica L. , Tarnopolsky Mark A. , Phillips Stuart M. 
Published: July 2010

AbstractWe determined the effectiveness of low‐volume resistance exercise (EX) for the attenuation of loss of muscle mass and strength during leg immobilization. Men (N = 5) and women (N = 12, age 24 ± 5 years, body mass index 25.4 ± 3.6 kg/m2) were divided into two groups: exercise (EX; n = 12) and control (CON; n = 5). Subjects wore a knee brace on one leg that prevented weight bearing for 14 days. Resistance exercise (EX; 80% of maximal) was performed by the immobilized limb every other day. Immobilization induced a significant reduction (P < 0.05) in muscle fiber and thigh cross‐sectional area (CSA), isometric knee extensor, and plantarflexor strength in the CON (P < 0.01) but not in the EX group. There were significant losses in triceps surae CSA in the CON and EX groups (P < 0.05), but the losses were greater in CON subjects (P < 0.01). A minimal volume (140 contractions in 14 days) of resistive exercise is an effective countermeasure against immobilization‐induced atrophy of the quadriceps femoris but is only partially effective for the triceps surae. Muscle Nerve, 2010
Clinicians' views on the feasibility of surgical randomized trials in urogynecology: Results of a questionnaire survey
Authors: Bakali Evangelia , Pitchforth Emma , Tincello Douglas G. , Kenyon Sara , Slack Mark , Toozs‐Hobson Philip , Mayne Christopher , Jones David R. , Taylor David 
Published: July 2010

AbstractAimsTo survey the views of clinicians (urologists and gynecologists) about a proposed randomized surgical trial comparing two approaches for the treatment of women with urinary incontinence and vaginal prolapse.MethodsA questionnaire survey nested within a pilot randomized controlled trial of colposuspension versus anterior repair plus TVT (CARPET1) for women with incontinence and anterior vaginal prolapse. Members of the UK Continence Society, British Society of Urogynaecology, and International Continence Society were sent a single electronic mailing of semi‐structured questionnaires containing closed and open questions and free text response boxes. Free text responses were analyzed using a thematic qualitative analysis.ResultsOne hundred fifty‐seven questionnaires were returned, from a potential total of 400 from UK and 1,700 international respondents. Fifty‐eight percent thought the trial ethical, 44% desirable, and 47% feasible. Thirty‐three percent would recruit to the full study, and 22% would enroll themselves or their partner. Analysis of free text responses identified three themes impacting participation: issues of patient choice and consent; clinicians' views of perceived benefit and complications of the two arms; and issues about the chosen trial design.ConclusionsThis study highlights the difference between collective and individual equipoise and their impact upon surgical trials. Clinicians held strong views preventing them from regarding the study favorably. Difficulty with relinquishing control over choice of procedure appeared central. These findings support the growing evidence in favor of detailed qualitative pilot work for surgical trials. The role of expertise‐based randomization deserves further consideration. Neurourol. Urodyn. 30:69–74, 2011. © 2010 Wiley‐Liss, Inc.
Mechanisms involved in the nitric oxide independent inhibitory neurotransmission to the pig urinary bladder neck
Authors: Martínez‐Saénz Ana , Barahona María Victoria , Orensanz Luis M. , Recio Paz , Bustamante Salvador , Benedito Sara , Carballido Joaquín , García‐Sacristán Albino , Prieto Dolores , Hernández Medardo 
Published: July 2010

AbstractAimsThe current study investigates the mechanisms involved in nitric oxide (NO)‐independent, nonadrenergic, noncholinergic (NANC) inhibitory neurotransmission to the pig urinary bladder neck.MethodsUrothelium‐denuded strips were mounted in organ baths containing physiological saline solution (PSS) at 37°C for isometric force recordings. The relaxations to electrical field stimulation (EFS) were carried out on strips treated with guanethidine, atropine and NG‐nitro‐L‐arginine, to block noradrenergic neurotransmission, muscarinic receptors and NO synthase, respectively, and precontracted with phenylephrine.ResultsEFS (1–16 Hz) produced frequency‐dependent relaxations which were abolished by the blockade of neuronal voltage‐activated Na+ channels. Nonselective and selective inhibition of COX and COX‐1, respectively, and blockade of Na+–K+ ATPase reduced the EFS‐induced relaxations. However, blockade of COX‐2, soluble guanylyl cyclase, large‐, intermediate‐ and small‐conductance Ca2+‐activated K+ channels, ATP‐dependent K+ channels, voltage‐gated K+ channels, cAMPc‐dependent protein kinase (PKA) and cGMP‐dependent protein kinase (PKG) failed to modify the nerve‐mediated relaxations.ConclusionsThe NO‐independent inhibitory neurotransmission to the pig urinary bladder neck is mediated, in part, through prostanoids release from a COX‐1 pathway, and through activation of the Na+–K+ ATPase. PKA and PKG pathways and postjunctional K+ channels do not appear to be involved in the NO‐independent nerve‐mediated relaxations. Neurourol. Urodyn. 30:151–157, 2011. © 2010 Wiley‐Liss, Inc.
Accuracy of post‐void residual urine volume measurement using a portable ultrasound bladder scanner with real‐time pre‐scan imaging
Authors: Park Yong Hyun , Ku Ja Hyeon , Oh Seung‐June 
Published: July 2010

AbstractAimsTo evaluate whether the bladder scanner with real‐time pre‐scan imaging (RPI) is superior to the conventional bladder scanner in measuring post‐void residual urine (PVR) volume.MethodsSixty‐seven patients with voiding dysfunction were subjected to PVR volume measurements. The PVR volume was measured three times by two experienced examiners using bladder scanners with (BioCon‐500, Mcube Technology, Seoul, Korea) or without (BVI‐3000 BladderScan, Verathon, WA) RPI. Immediately after the procedure, urethral catheterization was performed to obtain true volume. The accuracy and variability of measurements were compared between the two devices and correlation coefficients were obtained.ResultsThe Pearson correlation coefficients between the PVR volume measured by each device and the true volume were 0.932 for the bladder scanner without RPI and 0.950 for the bladder scanner with RPI. The bladder scanner without RPI tended to overestimate the true volume in moderate volume ranges (>100 ml) by a mean percentage of differences of volume (PDV) of 16.3%, while the bladder scanner with RPI underestimated the true volume in the whole volume range by a mean PDV of −14.1% (P < 0.001). Repeated measures ANOVA showed no significant interobserver variability (P = 0.977 for the bladder scanner without RPI and P = 0.853 for the bladder scanner with RPI) or intraobserver variability (P = 0.660 for the bladder scanner without RPI and P = 0.271 for the bladder scanner with RPI).ConclusionsOur results showed that exact pointing to the bladder prior to actual measurement of bladder volume with RPI seems to reduce the variability of the measured values. Neurourol. Urodynam. 30:335–338, 2011. © 2010 Wiley‐Liss, Inc.