bluuebunny/crossref_metadata_2025_split huggingface dataset:
Digoxin use and the risk of cancers of the corpus uteri, ovary and cervix
Authors: Biggar Robert J. , Wohlfahrt Jan , Melbye Mads 
Published: September 2011

AbstractDigoxin is a phyto‐estrogen capable of inducing hormonal effects. Use has been associated with increased risk of breast cancer, an estrogen‐sensitive malignancy. The incidence of corpus uteri (uterus) cancer is also strongly increased with exposure to estrogens. Therefore, we evaluated whether digoxin use might also increase its incidence. In all women in Denmark, we identified digoxin users from 1995 through 2008 using a nationwide pharmacy registry system. Cancer occurrence was obtained from Danish Cancer Registry. Relative risk was determined using incidence risk ratios (RR) and 95% confidence intervals (CIs) relative to non‐users after adjustment for age‐ and calendar‐time. For ovarian and cervical cancers, RRs in users and non‐users were similarly evaluated, these cancers representing gynecological cancers with weak or no associations to estrogen exposure. Of 2.1 million women, 104,648 (4.9%) had digoxin exposure and 137,493 6.5% had exposure to angina drugs but not digoxin during the study period. For uterus cancer, the RR was increased in current digoxin users (1.48, 95% CI: 1.32–1.65; N = 350). Incidence was marginally increased in former users. For ovary and cervix cancers, RRs in current digoxin users were 1.06 (95% CI: 0.92–1.22; N = 207) and 1.00 (95% CI: 0.79–1.25; N = 81), respectively. We examined risks in women using angina drugs but not digoxin to determine whether being under cardiac care affected risk. Among women using angina drugs only, RRs for uterus, ovary or cervix cancers were not statistically significant. We conclude that women currently using digoxin, a phyto‐estrogen, have an increased risk of developing uterus cancers.
Synthesis of novel folate conjugated fluorescent nanoparticles for tumor imaging
Authors: Hou Jie , Zhang Qi , Li Xia , Tang Yu , Cao Mei‐rong , Bai Fang , Shi Qian , Yang Cui‐hong , Kong De‐ling , Bai Gang 
Published: September 2011

AbstractA novel folate fluorescent nanoconjugate was synthesized and used for detection of cancer cells overexpressing the folate receptor (FR). The folate conjugate (PCMS‐NA‐FA) was synthesized by conjugating folic acid (FA) and 4‐ethylnyl‐N‐ethyl‐1, 8‐naphthalimide (NA) to the polychloromethylstyrene (PCMS) functionalized with azido group (PCMS‐N3) through click reaction. The obtained conjugate had clear structure and could form PCMS‐NA‐FA nanoparticles with particle size around 86 nm in aqueous solution. Ability of PCMS‐NA‐FA targeting to cancerous cells was investigated by comparing the uptake of the nanoparticles by human adenocarcinoma HeLa cells and by non‐FR expressing human lung carcinoma A549 cells. Specificity of the PCMS‐NA‐FA nanoparticles targeting on FRs was verified with cellular uptake inhibition assay, in which HeLa cells were incubated with both nanoconjugate and free FA. In addition, the specificity was also confirmed by the collocation of the immunofluorescence staining of anti‐FR and the cellular uptake of the PCMS‐NA‐FA nanoparticles. Furthermore, the organ distribution of this folate nanoconjugate was studied on HeLa cell‐bearing mice via frozen slicing, and the results showed that the folate nanoparticles were preferentially accumulated in the tumor site rather than other tissues, indicating the desired specificity for tumor targeting and imaging. All these findings suggested that this practical synthetic strategy can potentially facilitate the preparation of multifunctional imaging probe in biology and diagnosis of disease. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
The roles of connective tissue growth factor and integrin‐linked kinase in high glucose‐induced phenotypic alterations of podocytes
Authors: Dai Hou‐Yong , Zheng Min , Lv Lin‐Li , Tang Ri‐Ning , Ma Kun‐Ling , Liu Dan , Wu Min , Liu Bi‐Cheng 
Published: September 2011

AbstractEmerging evidence has suggested that podocytes undergo epithelial–mesenchymal transition (EMT) in diabetic nephropathy (DN). Connective tissue growth factor (CTGF) and integrin‐linked kinase (ILK) are involved in the progression of DN. However, the underlying mechanisms of EMT are not well understood. The study aimed to investigate the roles of CTGF and ILK in high glucose‐induced phenotypic alterations of podocytes and determine whether ILK signaling is downstream of CTGF. The epithelial marker of nephrin and the mesenchymal marker of desmin were investigated by real‐time RT‐PCR and Western blotting. The results demonstrated that podocytes displayed a spreading, arborized morphology in normal glucose, whereas they had a cobblestone morphology in high glucose conditions, accompanied by decreased nephrin expression and increased desmin expression, suggesting podocytes underwent EMT. In response to high glucose, CTGF and ILK expression in podocytes were increased in a dose‐ and time‐dependent manner, whereas the increase did not occur in the osmotic control. Furthermore, the inhibition of CTGF with anti‐CTGF antibody prevented the phenotypic transition, as demonstrated by the preservation of epithelial morphology, the suppression of high glucose‐induced desmin overexpression and the restoration of nephrin. Of note, the upregulation of ILK induced by high glucose was partially blocked by the inhibition of CTGF. In summary, these findings suggested that CTGF and ILK were involved in high glucose‐induced phenotypic alterations of podocytes. ILK acted as a downstream kinase of CTGF and high glucose‐induced ILK expression might occur through CTGF‐dependent and ‐independent pathways. J. Cell. Biochem. 113: 293–301, 2012. © 2011 Wiley Periodicals, Inc.
Down‐regulation of the cavin family proteins in breast cancer
Authors: Bai Lin , Deng Xiaoli , Li Qian , Wang Miao , An Wei , A Deli , Gao Zhuo , Xie Yuntao , Dai Yifan , Cong Yu‐Sheng 
Published: September 2011

AbstractCaveolae are abundant membrane domain on the cell surface of many mammalian cell types and are implicated in a wide range of physiological processes. The caveolae structural protein caveolin‐1 is often mutated or deregulated in cancer, and cavin family protein serum deprivation response factor‐related gene product that binds to C‐kinase (SRBC) has been found to be epigenetically inactivated in lung, breast, and gastric cancer. Both caveolin‐1 and SRBC have been proposed to function as tumor suppressors. Polymerase 1 and transcript release factor (PTRF) is the essential component for caveolae formation. The regulation of PTRF expression in cancer has not been characterized. We report here that the cavin family protein PTRF, SRBC and serum deprivation response protein were down regulated in breast cancer cell lines and breast tumor tissue. We further show that down‐regulation of PTRF in breast cancer cells was associated with the promoter methylation. As caveolin‐1 and cavin family proteins are required for caveolae formation and function, the reported tumor suppression function of caveolin‐1 and SRBC may be due to the deregulation of caveolae and its down‐stream signaling. Thus, the caveolae is a potential therapeutic target and the expression of cavin family proteins could be a useful prognostic indicator of breast cancer progression. J. Cell. Biochem. 113: 322–328, 2012. © 2011 Wiley Periodicals, Inc.
Physiological loading of tendons induces scleraxis expression in epitenon fibroblasts
Authors: Mendias Christopher L. , Gumucio Jonathan P. , Bakhurin Konstantin I. , Lynch Evan B. , Brooks Susan V. 
Published: September 2011

AbstractScleraxis is a basic helix–loop–helix transcription factor that plays a central role in promoting fibroblast proliferation and matrix synthesis during the embryonic development of tendons. Mice with a targeted inactivation of scleraxis (Scx−/−) fail to properly form limb tendons, but the role that scleraxis has in regulating the growth and adaptation of tendons of adult organisms is unknown. To determine if scleraxis expression changes in response to a physiological growth stimulus to tendons, we subjected adult mice that express green fluorescent protein (GFP) under the control of the scleraxis promoter (ScxGFP) to a 6‐week‐treadmill training program designed to induce adaptive growth in Achilles tendons. Age matched sedentary ScxGFP mice were used as controls. Scleraxis expression was sparsely observed in the epitenon region of sedentary mice, but in response to treadmill training, scleraxis was robustly expressed in fibroblasts that appeared to be emerging from the epitenon and migrating into the superficial regions of tendon fascicles. Treadmill training also led to an increase in scleraxis, tenomodulin, and type I collagen gene expression as measured by qPCR. These results suggest that in addition to regulating the embryonic formation of limb tendons, scleraxis also appears to play an important role in the adaptation of adult tendons to physiological loading. © 2011 Orthopaedic Research Society. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:606–612, 2012
Role of angiogenesis after muscle derived stem cell transplantation in injured medial collateral ligament
Authors: Nishimori Makoto , Matsumoto Tomoyuki , Ota Shusuke , Kopf Sebastian , Mifune Yutaka , Harner Christopher , Ochi Mitsuo , Fu Freddie H. , Huard Johnny 
Published: September 2011

AbstractWe performed this study to investigate the therapeutic role of vascular endothelial growth factor (VEGF) in medial collateral ligament (MCL) healing. Murine muscle derived stem cells (MDSCs) obtained via the preplate technique were retrovirally transduced to express: (1) VEGF and nLacZ (MDSC‐VEGF), (2) soluble fms‐like tyrosine kinase‐1 (sFLT1, a VEGF‐specific antagonist) and nLacZ (MDSC‐sFLT1), and (3) nLacZ (MDSC‐nLacZ). After transecting the MCL of immunodeficient rats, 5 × 105 cells of each of the transduction groups list above were transplanted into the MCL injury site. A control group was injected with phosphate‐buffered saline (PBS) only. Immunohistochemical staining demonstrated that there were more Isolectin B4 and β‐galactosidase double positive cells in the rats transplanted with MDSC‐VEGF transduced cells than the other groups at week 1. Capillary density was significantly higher in the MDSC‐VEGF group than the other groups at week 2; however, there were no significant differences in the biomechanical assessment between the MDSC‐VEGF and MDSC‐nLacZ groups. On the other hand, the MDSC‐sFLT1 group revealed a lower capillary density than the other two groups and the functional ligament healing of the MDSC‐sFLT1 group was significantly decreased compared to the other groups when assessed biomechanically. The findings of the present study suggest that angiogenesis plays a critical role in the healing process of injured MCL. © 2011 Orthopaedic Research Society. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:627–633, 2012
Lysine392, a K63‐linked ubiquitination site in NEMO, mediates inflammatory osteoclastogenesis and osteolysis
Authors: Alhawagri Muhammad , Yamanaka Yasuhiro , Ballard Dean , Oltz Eugene , Abu‐Amer Yousef 
Published: September 2011

AbstractPMMA particles released from bone implants are considered major contributor to osteolysis and subsequent implant failure. Although the ensuing inflammatory response has been described, the mechanisms underlying PMMA particulate‐induced osteolysis remain enigmatic. In previous studies, we have established that activation of Nuclear factor kappa‐B (NF‐κB) and MAP kinase pathways plays a central role in the pathogenesis of inflammatory osteolysis. Specifically, we have shown that impeding IKK complex assembly, and thus subsequent NF‐κB activation, dampens particle‐induced osteolysis. The IKK complex consists of IKKα, IKKβ, and IKKγ, also known as NEMO. NEMO has no catalytic activity and serves as a scaffold protein facilitating assembly and distal activation of NF‐κB signaling. In fact, blocking binding of NEMO with IKKα/β abolishes NF‐κB activity. In the current study, we identify Lysine 392 residue in NEMO as crucial mediator of PMMA particle‐induced inflammatory osteoclastogenesis and osteolysis. Using mice in which NEMO‐K392R mutation has been introduced, we provide evidence that PMMA‐induced osteoclasts and osteolytic responses are impaired. Furthermore, we show that this impairment is likely due to poor activation of NF‐κB and Erk, but not other MAP kinases. Our findings suggest that NEMO Lysine392, a well‐established K63‐linked polyubiquitination site, is an important mediator of PMMA‐induced osteolysis. Therefore, this NEMO motif should be considered as a target to combat PMMA particle‐induced osteolysis. © 2011 Orthopaedic Research Society. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:554–560, 2012
Holocene changes in precipitation seasonality in the western Mediterranean Basin: a multi‐species approach using δ13C of archaeobotanical remains
Authors: Aguilera M. , Ferrio J. P. , Pérez G. , Araus J. L. , Voltas J. 
Published: September 2011

AbstractPrecipitation has been of utmost importance in shaping the evolution of landscapes and human settlements in the Mediterranean. However, information on seasonal precipitation patterns through the Holocene is scarce. This study attempts to quantify the evolution of seasonal precipitation in the East Iberian Peninsula (5000 BC to AD 600) based on the carbon isotope composition (δ13C) of archaeobotanical remains. Data on Holm oak, Aleppo pine and small‐grain cereals were combined, and precipitation was inferred from models relating present‐day records to the δ13C of modern samples. Subsequently, charred grains were used as a proxy for ancient moisture during April–May, whereas oak and pine charcoals provided complementary rainfall estimates for September–December and January–August, respectively. The results reveal aridity changes throughout the Holocene in the western Mediterranean. Past spring–summer precipitation was consistently higher than at present. In contrast, autumn and early winter precipitation showed stronger fluctuations, particularly during the first millennium BC, and often exhibited values below those of the present. The high contribution of autumn precipitation to the annual water budget, typical of the present Mediterranean climate, was definitively established at the beginning of the current era. This study shows how a combination of species holding complementary environmental signals can contribute to a wider knowledge of local precipitation dynamics. Copyright © 2011 John Wiley & Sons, Ltd.
A One Pot, One Step Method for the Preparation of Clickable Hydrogels by Photoinitiated Polymerization
Authors: Yilmaz Gorkem , Kahveci Muhammet U. , Yagci Yusuf 
Published: September 2011

AbstractCurrent preparation methods for hydrogels based on redox or photopolymerization of water soluble monomers are simple to use, and flexible, but have the drawback of requiring additional modification steps for tuning or introducing properties for specific purposes. We have devised a simple and rapid synthetic strategy to prepare hydrogels possessing reactive sites to incorporate any molecules of interest by “Click Chemistry”. The strategy is based on the use of propargyl acrylamide (PAm) as comonomer together with acrylamide (AAm) and N,N′‐methylene bisacrylamide (BAAm) as crosslinker in photoinitiated polymerization. With the selective reactivity of photochemically generated free radicals towards acrylic function of PAm, hydrogels with clickable acetylene groups can be prepared in one pot, one step manner. Based on the acetylene functionality, any molecule possessing azide groups can be conjugated onto hydrogel by “Click Chemistry” as demonstrated on the example of fluoroscent azide functional pyrene.
Pediatric Asthma: Natural History, Assessment, and Treatment
Authors: Herzog Ronit , Cunningham‐Rundles Susanna 
Published: September 2011

AbstractWheezing and childhood asthma are not synonymous but rather comprise a heterogeneous group of conditions that have different outcomes over the course of childhood. Most infants who wheeze have a transient condition associated with diminished airway function at birth and have no increased risk of asthma later in life. However, children with persistent wheezing throughout childhood and frequent exacerbations represent the main challenge today. Studying the natural history of asthma is important for the understanding and accurate prediction of the clinical course of different phenotypes. To date, a great improvement has been achieved in reducing the frequency of asthma symptoms. However, neither decreased environmental exposure nor controller treatment, as recommended by the recent National Asthma Education And Prevention Program, can halt the progression of asthma in childhood or the development of persistent wheezing phenotype. This review focuses on the recent studies that led to the current understanding of asthma phenotypes in childhood and the recommended treatments. Mt Sinai J Med 78:645–660, 2011. © 2011 Mount Sinai School of Medicine
Treatment of Asthma and Food Allergy With Herbal Interventions From Traditional Chinese Medicine
Authors: Li Xiu‐Min 
Published: September 2011

AbstractPrevalence of asthma and allergy has increased over the past 2–3 decades in Westernized countries. Despite increased understanding of the pathogenesis of asthma and allergic diseases, control of severe asthma is still difficult. Asthma is also associated with a high prevalence of anxiety, particularly in adolescents. There is no effective treatment for food allergy. Food allergy is often associated with severe and recalcitrant eczema. Novel approaches for treatment of asthma and food allergy and comorbid conditions are urgently needed. Traditional Chinese medicine, used in Asia for centuries, is beginning to play a role in Western healthcare. There is increasing scientific evidence supporting the use of traditional Chinese medicine for asthma treatment. Since 2005, several controlled clinical studies of “antiasthma” herbal remedies have been published. Among the herbal medicines, antiasthma herbal medicine intervention is the only antiasthma traditional Chinese medicine product that is a Food and Drug Administration investigational new drug that has entered clinical trials in the United States. Research into the effects and mechanisms of action of antiasthma herbal medicine intervention in animal models is actively being pursued. Research on traditional Chinese medicine herbal medicines for treating food allergy is rare. The herbal intervention Food Allergy Herbal Formula‐2 is the only Food and Drug Administration botanical investigational new drug under investigation as a multiple food allergy therapy. This review article discusses promising traditional Chinese medicine interventions for asthma, food allergy, and comorbid conditions, and explores their possible mechanisms of action. Mt Sinai J Med 78:697–716, 2011. © 2011 Mount Sinai School of Medicine
Fasciculation potentials in amyotrophic lateral sclerosis and the diagnostic yield of the Awaji algorithm
Authors: Higashihara Mana , Sonoo Masahiro , Imafuku Ichiro , Fukutake Toshio , Kamakura Keiko , Inoue Kiyoharu , Hatanaka Yuki , Shimizu Teruo , Tsuji Shoji , Ugawa Yoshikazu 
Published: September 2011

AbstractIntroduction: The role of fasciculation potentials (FPs) in the diagnosis of amyotrophic lateral sclerosis (ALS) has been underrated. The Awaji algorithm has restored the value of FPs. Our aim was to test the diagnostic yield of the Awaji algorithm, with consideration of FPs. Methods: Subjects consisted of 139 consecutive ALS patients retrospectively enrolled over 5 years. At presentation we evaluated the diagnostic categories using the revised El Escorial Criteria (R‐EEC) and the Awaji algorithm. Results: The percentage of patients classified as confirmed ALS, clinically probable (laboratory‐supported), or higher was 43% using the R‐EEC and 37% using the Awaji algorithm. Thirteen patients with upper motor neuron signs only in one body region showed a decrease in their category using the Awaji algorithm. FPs were observed in 89% of ALS patients and were frequent in proximal muscles. Conclusion: The sensitivity of the Awaji algorithm is lower than that of the R‐EEC. Muscle Nerve, 2012
The interprotein scoring noises in glide docking scores
Authors: Wang Wei , Zhou Xi , He Wanlin , Fan Yi , Chen Yuzong , Chen Xin 
Published: September 2011

AbstractSmall molecule drugs are rarely selective enough to interact solely with their designated targets. Unintended “off‐target” interactions often lead to side effects, but also serendipitously lead to new therapeutic uses. Identification of the off‐targets of a compound is therefore of significant value to the evaluation of its developmental potential. In computational biology, the strategy of “reverse docking” has been introduced to predict the targets of a compound, which uses a compound to virtually screen a library of proteins, reversing the bait and prey in “normal” docking screenings. The present study shows that, in reverse docking, additional optimization of the scoring function may help to improve the target prediction accuracy. In a case study with the Glide scores, we found that only 57% of the ligand–protein relationships could be correctly identified in a library of 58 complexes whose crystal binding conformations were all able to be accurately reproduced. This was likely a result of the constant over‐ or under‐estimation of the scores for specific proteins. In other words, there were interprotein noises in the Glide scores. Introducing a correction term based on protein characteristics improved the target‐prediction accuracy by 27% (57–72%). It is our hope that this focused discussion on the Glide scores would invite further efforts to characterize and normalize this type of interprotein noises in all docking scores, so that better target prediction accuracy can be achieved with the strategy of reverse docking. Proteins 2012; © 2011 Wiley Periodicals, Inc.
Doppler radar observations of non‐occluding, cyclic vortex genesis within a long‐lived tornadic storm over southern England
Authors: Clark M. R. 
Published: September 2011

AbstractOn 3 November 2009 a long‐lived tornadic storm developed close to the apex of a small frontal wave moving eastwards over southern England. Ten tornadoes and several instances of non‐tornadic wind damage occurred along a narrow path extending for over 120 km. The storm passed within 5 km of two of the radars in the Met Office's network, providing an opportunity for detailed observation. Initial development was in the form of an intense segment of line convection at the northern flank of the frontal wave and associated deepening surface mesolow (diameter 60–70 km). The line evolved rapidly; the southern portion bowed out to form a transient ‘S’‐shaped echo before dissipating. The northern section persisted, leaving a hook‐shaped storm which became quasi‐steady in overall echo shape.Radars revealed the cyclic development of five discrete low‐level mesovortices (diameter 1–4 km) between 1130 and 1330 UTC, along a zone of intense cyclonic vertical vorticity at the southeastern edge of the storm. These vortices intensified rapidly (typically from initial detection to maximum observed differential velocity in ∼10 min), some attaining low‐level differential velocities exceeding 40 m s−1. However, significant differential velocities (>20 m s−1) were not observed above 2.5 km above ground level, and no persistent mid‐level mesocyclone was present. The cyclic behaviour was unusual in that vortices were ‘non‐occluding’, moving southeastwards relative to the storm (to the right of the storm motion vector), away from the core. This is in contrast to the more commonly observed evolution of vortex occlusion (by storm downdraughts) and subsequent leftward and rearward storm‐relative movement during decay. Copyright © 2011 British Crown copyright, the Met Office. Published by JohnWiley & Sons Ltd.