bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving the quality of maternity services in Nepal through accelerated implementation of essential interventions by healthcare professional associations
Authors: Spira Cintia , Dhital Rolina , Jacob Sue , Dangal Ganesh , Gurung Geeta , Prasad Shrestha Laxman , Prasad Bista Krishna , Bajracharya Kiran , Bajrachayra Lata , Baral Gehanath , Maiya Kaway Nani , Rushawn Hamid , Cooper Peter , Day‐Stirk Frances , Berrueta Mabel , Gibbons Luz , García‐Elorrio Ezequiel , Belizán José M. 
Published: September 2018

AbstractObjectiveTo assess whether the implementation of a package of activities through the joint action of three international healthcare professional associations (HCPAs) increased the use of essential interventions (EIs) for delivery and neonatal care.MethodsA noncontrolled pre‐intervention versus post‐intervention study was conducted from June 13 to December 13, 2016, among women older than 18 years of age, who had delivered at one of two urban tertiary hospitals in Nepal.ResultsThe study included 9252 women. Minimal change was found after the implementation of EIs that were used frequently at baseline (e.g. social support during delivery in the emergency room, and promotion and support for early initiation of breastfeeding). By contrast, an increase was recorded for some EIs that had not been used regularly at baseline. For example, the rate of timely administration of prophylactic antibiotics before cesarean delivery increased from 0.0% (0/496) to 94.0% (409/435) at one hospital. Nonetheless, some EIs with low use at baseline did not show improvement after implementation (e.g. kangaroo mother care).ConclusionThe present study strengthened previous findings regarding the uptake of EIs following joint promotion by HCPAs in low‐income settings.
First‐in‐Asian Phase I Study of the Anti‐Fibroblast Growth Factor 23 Monoclonal Antibody, Burosumab: Safety and Pharmacodynamics in Adults With X‐linked Hypophosphatemia
Authors: Cheong Hae Il , Yoo Han‐Wook , Adachi Masanori , Tanaka Hiroyuki , Fujiwara Ikuma , Hasegawa Yukihiro , Harada Daisuke , Sugimoto Maiko , Okada Yosuke , Kato Masaki , Shimazaki Ryutaro , Ozono Keiichi , Seino Yoshiki 
Published: September 2018

ABSTRACTX‐linked hypophosphatemia (XLH) is a disease caused by abnormally elevated FGF23 levels, which cause persistent hypophosphatemia accompanied by subsequent reduction in bone mineralization that presents as rickets or osteomalacia. Burosumab is a fully human monoclonal antibody targeting FGF23 that is under development for the treatment of FGF23‐related hypophosphatemia including XLH. The safety, tolerability, and proof of concept of burosumab have been evaluated in patients with XLH in previous studies conducted in countries outside of Asia. The objective of this study was to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and expression of anti‐drug antibodies in Japanese and Korean adults with XLH. This was a multicenter, sequential dose‐escalation, open‐label, single‐dose study. This study began with cohort 1 (s.c. dose of burosumab 0.3 mg/kg), after which the dose was escalated sequentially in cohort 2 (s.c. dose of burosumab 0.6 mg/kg) and cohort 3 (s.c. dose of burosumab 1.0 mg/kg). The PK of burosumab were linear within the dose range of 0.3 to 1.0 mg/kg. The PD effects such as serum phosphorus concentration, serum 1,25[OH]2D3 concentration, and ratio of tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR) were elevated after a single s.c. administration. The area under the receiver‐operating characteristic curve from 0 to t (AUC0–t) values calculated using the change from baseline values of serum phosphorus, serum 1,25(OH)2D3, and TmP/GFR were correlated with the AUC0–t of burosumab. Furthermore, no serious adverse events (AEs), deaths, remarkable increase or decrease in the corrected calcium or intact PTH levels, or signs of nephrocalcinosis or its worsening were observed after treatment. Some AEs and drug‐related AEs were observed; however, there were no clinically meaningful tendencies. The positive effects and acceptable safety profile seen in this study are encouraging for Japanese and Korean patients with XLH. © 2018 The Authors JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
TLR4 Promotes and DAP12 Limits Obesity‐Induced Osteoarthritis in Aged Female Mice
Authors: Kalaitzoglou Evangelia , Lopes Erika Barboza Prado , Fu Yao , Herron Jacquelyn C , Flaming Josiah M , Donovan Elise L , Hu Yanqing , Filiberti Adrian , Griffin Timothy M , Humphrey Mary Beth 
Published: September 2018

ABSTRACTAging and female sex are the strongest risk factors for nontraumatic osteoarthritis (OA); whereas obesity is a modifiable risk factor accelerating OA. Prior studies indicate that the innate immune receptor toll‐like receptor 4 (TLR4) mediates obesity‐induced metabolic inflammation and cartilage catabolism via recognition of damage‐associated molecular patterns and is increased with aging in OA joints. TLR4 responses are limited by innate immunoreceptor adapter protein DNAX‐activating protein of 12kDA (DAP12). We undertook this study to test the hypothesis that TLR4 promotes, whereas DAP12 limits, obesity‐accelerated OA in aged female mice. We fed 13‐ to 15‐month‐old female WT, TLR4 KO, and DAP12 KO mice a high‐fat diet (HFD) or a control diet for 12 weeks, and changes in body composition, glucose tolerance, serum cytokines, and insulin levels were compared. Knee OA was evaluated by histopathology and μCT. Infrapatellar fat pads (IFPs) were analyzed by histomorphometry and F4/80+ crown‐like structures were quantified. IFPs and synovium gene expression were analyzed using a targeted insulin resistance and inflammation array. All HFD‐treated mice became obese, but only WT and TLR4 KO mice developed glucose intolerance. HFD induced cartilage catabolism in WT and DAP12 KO female mice, but not in TLR4 KO mice. Gene‐expression analysis of IFPs and synovium showed significant differences in insulin signaling, adipokines, and inflammation between genotypes and diets. Unlike young mice, systemic inflammation was not induced by HFD in the older female mice independent of genotype. Our findings support the conclusion that TLR4 promotes and DAP12 limits HFD‐induced cartilage catabolism in middle‐aged female mice. © 2018 The Authors JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
Phosphoinositide‐dependent kinase 1–associated glycolysis is regulated by miR‐409‐3p in clear cell renal cell carcinoma
Authors: Wang Yongjun , He Yanfa , Bai Hongzhong , Dang Yi , Gao Jiangyan , Lv Pei 
Published: September 2018

AbstractClear cell renal cell carcinoma (ccRCC) is the most popular kidney cancer in adults. Metabolic shift toward aerobic glycolysis is a fundamental factor for ccRCC therapy. MicroRNAs (miRNAs) are thought to be important regulators in ccRCC development and progression. Phosphoinositide‐dependent kinase 1 (PDK1) is required for metabolic activation; however, the role of PDK1‐induced glycolytic metabolism regulated by miRNAs is unclear in ccRCC. So, the purpose of the current study is to elucidate the underlying mechanism in ccRCC cell metabolism mediated by PDK1. Our results revealed that miR‐409‐3p inhibited glycolysis by regulating PDK1 expression in ccRCC cells. We also found that miR‐409‐3p was regulated by hypoxia. Our results indicated that PDK1 facilitated ccRCC cell glycolysis, regulated by miR‐409‐3p in hypoxia.
Integrin alpha x stimulates cancer angiogenesis through PI3K/Akt signaling–mediated VEGFR2/VEGF‐A overexpression in blood vessel endothelial cells
Authors: Wang Jingshu , Yang Lina , Liang Fan , Chen Yaping , Yang Gong 
Published: September 2018

AbstractIntegrin alpha x (ITGAX), a member of the integrin family, usually serves as a receptor of the extracellular matrix. Recently, accumulating evidence suggests that ITGAX may be involved in angiogenesis in dendritic cells. Herein, we report a direct role of ITGAX in angiogenesis during tumor development. Overexpression of ITGAX in human umbilical vein endothelial cells (HUVECs) enhanced their proliferation, migration, and tube formation and promoted xenograft ovarian tumor angiogenesis and growth. Further study showed that overexpression of ITGAX activated the PI3k/Akt pathway, leading to the enhanced expression of c‐Myc, vascular endothelial growth factor‐A (VEGF‐A), and VEGF receptor 2 (VEGFR2), whereas, the treatment of cells with PI3K inhibitor diminished these effects. Besides, c‐Myc was observed to bind to the VEGF‐A promoter. By Co‐Immunoprecipitation (Co‐IP) assay, we manifested the interaction between ITGAX and VEGFR2 or the phosphorylated VEGFR2. Immunostaining of human ovarian cancer specimens suggested that endothelial cells of micro–blood vessels displayed strong expression of VEGF‐A, c‐Myc, VEGFR2, and the PI3K signaling molecules. Also, overexpression of ITGAX in HUVECs could stimulate the spheroid formation of ovarian cancer cells. Our study uncovered that ITGAX stimulates angiogenesis through the PI3K/Akt signaling–mediated VEGFR2/VEGF‐A overexpression during cancer development.
Matrix stiffness mediates stemness characteristics via activating the Yes‐associated protein in colorectal cancer cells
Authors: Tan Fengbo , Huang Yan , Pei Qian , Liu Heli , Pei Haiping , Zhu Hong 
Published: September 2018

AbstractMatrix stiffness is an essential physical microenvironment in solid cancer. However, its influence on cancer stemness still remains elusive. Colorectal cancer (CRC) cell line HCT‐116 was cultured in the matrix with various stiffness. The siYAP was applied to detect the changes of stemness markers. The cancer stemness markers, Yes‐associated protein (YAP), Lamin A/C and downstream protein molecules, and their activation were measured after the treatment with anti‐β1‐integrin and FAK inhibitors. In CRC tissue samples, collagen deposition and the expression of α‐SMA and CD133 were detected. The study found that the expression level of stemness markers and Lamin A/C increased as the matrix stiffness raised and was regulated by YAP activation in CRC stem cells. Inhibition of β1‐integrin and FAK activation in a high stiffness cell culture medium significantly decreased the activation of YAP, PI3K, and AKT. Collagen was highly deposited in the CRC invasive tumor front (ITF), and the expression of CD133 was higher in ITF compared with normal tissue and the tumor cells. Moreover, the expression level of α‐SMA was positively correlated with CD133 expression level. Together, our results suggest that activation of YAP in CRC plays an important role in the promotion of cancer stem cell properties by extracellular matrix stiffness in CRC.
Autophagy in osteoporosis: Relation to oxidative stress
Authors: Ezzat Sara , Louka Manal L , Zakaria Zeiad M , Nagaty Magda M , Metwaly Radwan G 
Published: September 2018

AbstractImpaired autophagy and oxidative stress are implicated in the development of many diseases. This study aimed to investigate the involvement of autophagy represented by autophagy‐related gene 7 (Atg7) and oxidative stress represented by superoxide dismutase 2 (SOD2) gene expression and enzyme activity in the pathogenesis of osteoporosis. Atg7 and SOD2 gene relative expression were evaluated by SYBR green quantitative real‐time‐polymerase chain reaction in the osteoporotic group (n = 26) versus the osteoporosis free group (n = 14). SOD2 enzyme activity was evaluated by colorimetric method in both study groups. Both Atg7 and SOD2 relative expression showed highly significant decrease (P < 0.01) between both groups. However, SOD2 enzyme activity showed no significant difference between the two groups. There was a significant direct correlation between Atg7 and SOD2 gene expression in both study groups. Atg7 relative expression showed significant (
P < 0.01) direct correlation with vitamin D serum levels and body mass index in osteoporotic group. In conclusion, both genes are involved in the pathogenesis of osteoporosis and this could be amenable to future therapeutic intervention.
LncRNA HOTAIR functions as a competing endogenous RNA to upregulate SIRT1 by sponging miR‐34a in diabetic cardiomyopathy
Authors: Gao Lu , Wang Xiaofang , Guo Sen , Xiao Lili , Liang Cui , Wang Zheng , Li Yapeng , Liu Yuzhou , Yao Rui , Liu Yuan , Zhang Yanzhou 
Published: September 2018

AbstractThe HOX transcript antisense RNA (HOTAIR) long noncoding RNA (lncRNA), a highly abundant and conserved imprinted gene, has been implicated in many essential biological processes and diseases. However, to date, the significance of HOTAIR in diabetic cardiomyopathy (DCM) has never been investigated. The current study was designed to determine whether DCM can be regulated by HOTAIR and to elucidate the related mechanism. In vivo, streptozotocin (STZ) was injected intraperitoneally to induce type 1 diabetes in mice. Cardiomyocyte specific HOTAIR overexpression was achieved using an adeno‐associated virus system 12 weeks after STZ injection. In vitro, H9c2 were used to explore the potential molecular mechanism of HOTAIR in the regulation of high‐glucose‐induced cardiomyocyte injury. Luciferase reporter assay and RNA immunoprecipitation (RIP) were performed to explore the relationship between HOTAIR, microRNA‐34a (miR‐34a), and Sirtuin 1 (SIRT1). HOTAIR expression was significantly decreased in diabetic mice hearts. Knockdown of HOTAIR in high glucose‐induced H9c2 resulted in increased oxidative injury, inflammation, and apoptosis in vitro. Cardiomyocyte‐specific overexpression of HOTAIR improved cardiac function, decreased oxidative stress and inflammation, and attenuated myocyte death in mice treated with STZ. Mechanistically, the expression of SIRT1/forkhead box protein O1 was significantly increased in the HOTAIR‐overexpressing hearts compared with the control hearts treated with STZ. Moreover, we found HOTAIR functioned as a molecular sponge of miR‐34a in H9c2 and SIRT1 was identified as a target of miR‐34a. Furthermore, the protective effects of HOTAIR on DCM was abolished in SIRT1 deficiency mice in vivo. HOTAIR protected against DCM via activation of the SIRT1 expression by sponging miR‐34a.
Ex vivo magnifying endoscopic observation of bile duct mucosa using narrowband imaging
Authors: Ishida Yusuke , Okabe Yoshinobu , Yasumoto Makiko , Naito Yoshiki , Nakama Yohei , Kitasato Yuhei , Ishikawa Hiroto , Hisaka Toru , Tsuruta Osamu , Torimura Takuji 
Published: September 2018

AbstractBackgroundDetailed endoscopic findings of the bile duct mucosa have not been fully established. This fundamental ex vivo study assesses the relationship between magnified endoscopic findings and pathological findings of the bile duct mucosa.MethodsForty‐one surgically resected common bile duct mucosae were investigated. Each common bile duct was cut open longitudinally for ex vivo endoscopic observation. A magnifying endoscope commonly used for the gastrointestinal tract was used, using both white light imaging and narrowband imaging. After pathological diagnosis, the association between the magnifying endoscopic findings and histopathology was evaluated.ResultsTotally, 39 non‐neoplastic mucosae and 13 neoplastic mucosae were evaluated. In 13 non‐neoplastic mucosae without inflammation, an oval‐shaped depressed area and a fine, regular network of microvessels were observed. These findings were not clearly seen or not seen at all in the non‐neoplastic mucosae with inflammation. Although vessels with loop‐like structure were observed on all eight papillary tumors of 13 neoplastic mucosae, no characteristic vessels were seen on the other five.ConclusionsIshida and colleagues assessed the association between magnifying endoscopic findings and histopathological findings of the bile duct mucosa ex vivo. Oval‐shaped, depressed areas and a fine, regular network of microvessels are characteristic features of normal bile duct mucosa, while loop structures may be indicative of a type of tumor vessel.
Picture level control method for bright regions of HDR images in power management of large AMOLED displays
Authors: Okada Takuya , Usui Takenobu , Yamamoto Toshihiro , Onoye Takao , Fujisaki Yoshihide 
Published: September 2018

AbstractHerein, a picture control method designed to facilitate power management of large active‐matrix organic‐light‐emitting‐diode displays is proposed. In this method, Hybrid Log‐Gamma (HLG) pictures are presented simply by multiplying the upper half of the picture level by the gain corresponding to the power suppression. HLG is a standard for high‐dynamic‐range images. The controlled picture is processed by nominal luminance transformation, as well as by color conversion from red–green–blue into hue–saturation–value (HSV) imagery. Results obtained via simulations show that high‐contrast HLG pictures can be better simulated by our proposed method than by currently used conventional methods. The simulation results also demonstrate that when the picture is presented using the proposed power consumption management method, both the dark and bright regions show less deterioration. In addition, through an examination of image histograms created to elucidate detail descriptions of simulated pictures in the red–green–blue and HSV color spaces, we found that using HSV color conversion in conjunction with the proposed method mitigates chromaticity shift and that the feasibility of HSV color conversions could be quantitatively clarified by the evaluation of color differences defined by the Euclidean distance in a uniform color space.
Light quantity, not photoperiod terminates diapause in the crustacean Daphnia
Authors: Ślusarczyk M. , Flis S. 
Published: September 2018

AbstractWhile light controls dormancy occurrence in various groups of organisms, it may play different roles in its initiation and termination. Seasonally changing photoperiod is frequently used to announce cyclical events and trigger diapause initiation in advance of seasonal changes. A similar role for photoperiod has often been uncritically extended to diapause termination. In the present study we investigated the role of photoperiod and light quantity in diapause termination of resting eggs of a freshwater crustacean. In a few tests, a cohort of resting eggs of Daphnia magna were incubated under various light conditions. A short‐day photoperiod appeared as successful as a long day or artificial one in reactivating resting eggs. The hatching proportion was more related to total light energy applied than to its temporal pattern. The hatching proportion increased asymptotically from 0% reported after 6 h of light exposition or shorter, to 32% after 48 h of total light period of moderate intensity (55 μmol m−2 s−1). Longer light exposition did not increase hatching success considerably. A 15 times lower light intensity (3.5 vs. 55 μmol m−2 s−1) applied for a given period of time (96 h) resulted in a 3 times lower hatching success. Our results challenge the common opinion of the decisive role of photoperiod in diapause termination and support the alternative light‐energy threshold hypothesis. It seems that the resting eggs of D. magna do not monitor seasonal changes of the photoperiod but reactivate after completion of the refractory period and accumulation of a certain amount of light energy dose.
Appendectomy and risk of Parkinson's disease in two large prospective cohorts of men and women
Authors: Palacios Natalia , Hughes Katherine C. , Cereda Emanuele , Schwarzschild Michael A. , Ascherio Alberto 
Published: September 2018

ABSTRACT
Background: Prior work on appendectomy and PD has produced mixed results. In this study we examined whether history of self‐reported appendectomy was related to risk of incident Parkinson's disease in the Nurses’ Health Study and the Health Professionals Follow‐up Study.
Methods: We used the Cox proportional hazards model to estimate the hazard ratio of Parkinson's disease associated with self‐report of appendectomy in men and women. Among women, we estimated the hazard ratio of Parkinson's disease associated with appendectomy for appendicitis and incidental appendectomy.
Results: In pooled analyses, self‐report of any appendectomy was not related to Parkinson's disease risk: the hazard ratio of Parkinson's disease comparing participants who reported any appendectomy with those who did not was 1.08 (95% confidence interval, 0.94‐1.23). In women, appendectomy for appendicitis, but not incidental appendectomy, was associated with a modestly elevated risk of Parkinson's disease (hazard ratio, 1.23 [95% confidence interval, 1.00‐1.50]).
Conclusions: Overall, this study suggests limited to no association between appendectomy and Parkinson's disease risk. © 2018 International Parkinson and Movement Disorder Society
3D high‐resolution imaging of 2‐hydroxyglutarate in glioma patients using DRAG‐EPSI at 3T in vivo
Authors: An Zhongxu , Tiwari Vivek , Baxter Jeannie , Levy Michael , Hatanpaa Kimmo J. , Pan Edward , Maher Elizabeth A. , Patel Toral R. , Mickey Bruce E. , Choi Changho 
Published: September 2018

PurposeTo develop 3D high‐resolution imaging of 2‐hydroxyglutarate (2HG) at 3T in vivo.MethodsEcho‐planar spectroscopic imaging with dual‐readout alternated‐gradients (DRAG‐EPSI), which was recently reported for 2D imaging of 2HG at 7T, was tested for 3D imaging of 2HG at 3T. The frequency drifts and acoustic noise induced by DRAG‐EPSI were investigated in comparison with conventional EPSI. Four patients with IDH‐mutant gliomas were enrolled for 3D imaging of 2HG and other metabolites. A previously reported 2HG‐tailored TE 97‐ms PRESS sequence preceded the DRAG‐EPSI readout gradients. Unsuppressed water, acquired with EPSI, was used as reference for multi‐channel combination, eddy‐current compensation, and metabolite quantification. Spectral fitting was conducted with the LCModel using in‐house basis sets.ResultsWith gradient strength of 4 mT/m and slew rate of 20 mT/m/ms, DRAG‐EPSI produced frequency drifts smaller by 5.5‐fold and acoustic noise lower by 25 dB compared to conventional EPSI. In a 19‐min scan, 3D DRAG‐EPSI provided images of 2HG with precision (CRLB <10%) at a resolution of 10 × 10 × 10 mm3 for a field of view of 240 × 180 × 80 mm3. 2HG was estimated to be 5 mM in a pre‐treatment patient. In 3 post‐surgery patients, 2HG estimates were 3–6 mM, and the 2HG distribution was different from the water‐T2 image pattern or highly concentrated in the post‐contrast enhancing region.ConclusionTogether with 2HG‐optimized PRESS, DRAG‐EPSI provides an effective tool for reliable 3D high‐resolution imaging of 2HG at 3T in vivo.