bluuebunny/crossref_metadata_2025_split huggingface dataset:
Astroglial Cx30 sustains neuronal population bursts independently of gap‐junction mediated biochemical coupling
Authors: Pannasch Ulrike , Dossi Elena , Ezan Pascal , Rouach Nathalie 
Published: February 2019

AbstractAstroglial networks mediated by gap junction channels contribute to neurotransmission and promote neuronal coordination. Connexin 30, one of the two main astroglial gap junction forming protein, alters at the behavioral level the reactivity of mice to novel environment and at the synaptic level excitatory transmission. However, the role and function of Cx30 at the neuronal network level remain unclear. We thus investigated whether Cx30 regulates neuronal population bursts and associated convulsive behavior. We found in vivo that Cx30 is upregulated by kainate‐induced seizures and that it regulates in turn the severity of associated behavioral seizures. Using electrophysiology ex vivo, we report that Cx30 regulates aberrant network activity via control of astroglial glutamate clearance independently of gap‐junction mediated biochemical coupling. Altogether, our results indicate that astroglial Cx30 is an important player in orchestrating neuronal network activity.
Metformin promotes survivin degradation through AMPK/PKA/GSK‐3β‐axis in non–small cell lung cancer
Authors: Luo Zhuang , Chen Wei , Wu Wenjuan , Luo Wei , Zhu Tingting , Guo Gang , Zhang Liyan , Wang Chu , Li Min , Shi Shaoqing 
Published: February 2019

AbstractMetformin, a first‐line antidiabetic drug, has been reported with anticancer activities in many types of cancer. However, its molecular mechanisms remain largely unknown. As a member of inhibitor of apoptosis proteins, survivin plays an important role in the regulation of cell death. In the present study, we investigated the role of survivin in metformin‐induced anticancer activity in non–small cell lung cancer in vitro. Metformin mainly induced apoptotic cell death in A549 and H460 cell lines. It remarkably suppressed the expression of survivin, decreased the stability of this protein, then promoted its proteasomal degradation. Moreover, metformin greatly suppressed protein kinase A (PKA) activity and induced its downstream glycogen synthase kinase 3β (GSK‐3β) activation. PKA activators, both 8‐Br‐cAMP and forskolin, significantly increased the expression of survivin. Consistently both GSK‐3β inhibitor LiCl and siRNA restored the expression of survivin in lung cancer cells. Furthermore, metformin induced adenosine 5′‐monophosphate‐activated protein kinase (AMPK) activation. Suppression of the activity of AMPK with Compound C reversed the degradation of survivin induced by metformin, and meanwhile, restored the activity of PKA and GSK‐3β. These results suggest that metformin kills lung cancer cells through AMPK/PKA/GSK‐3β‐axis–mediated survivin degradation, providing novel insights into the anticancer effects of metformin.
miR‐148a‐3p regulates proliferation and apoptosis of bovine muscle cells by targeting KLF6
Authors: Song Chengchuang , Yang Jiameng , Jiang Rui , Yang Zhaoxin , Li Hui , Huang Yongzhen , Lan Xianyong , Lei Chuzhao , Ma Yun , Qi Xinglei , Chen Hong 
Published: February 2019

AbstractSkeletal muscle development is regulated by a series of regulatory factors, and also including noncoding RNA, especially microRNAs (miRNAs). Recently, miR‐148a has been found to be involved in murine C2C12 differentiation by targeting ROCK1. However, the function of miR‐148a‐3p for the proliferation and apoptosis of bovine muscle cells has not been determined. In this study, we found that miR‐148a‐3p was highly expressed in fetal bovine skeletal muscle and exhibited a decreasing trend in muscle cells during its growth phase. Functional studies indicated that gain of miR‐148a‐3p inhibited the proliferation of bovine muscle cells and promoted apoptosis. Conversely, interference with miR‐148a‐3p inhibitor promoted muscle cell proliferation and inhibited its apoptosis. Mechanistically, KLF6 was confirmed as a new potential target gene of miR‐148a‐3p by TargetScan software prediction and the dual‐luciferase assay verification. Additionally, after a gain or loss of KLF6, the function of KLF6 for muscle cell proliferation and apoptosis was opposite to that of miR‐148a‐3p. Collectively, these findings proposed a novel avenue whereby miR‐148a‐3p impeded bovine myoblast cell proliferation and promoted apoptosis through the posttranscriptional downregulation of KLF6.
Tumor‐derived exosomes: Implication in angiogenesis and antiangiogenesis cancer therapy
Authors: Aslan Cynthia , Maralbashi Sepideh , Salari Farhad , Kahroba Houman , Sigaroodi Faraz , Kazemi Tohid , Kharaziha Pedram 
Published: February 2019

AbstractTumor cells utilize different strategies to communicate with neighboring tissues for facilitating tumor progression and invasion, one of these strategies has been shown to be the release of exosomes. Exosomes are small nanovesicles secreted by all kind of cells in the body, especially cancer cells, and mediate cell to cell communications. Exosomes play an important role in cancer invasiveness by harboring various cargoes that could accelerate angiogenesis. Here first, we will present an overview of exosomes, their biology, and their function in the body. Then, we will focus on exosomes derived from tumor cells as tumor angiogenesis mediators with a particular emphasis on the underlying mechanisms in various cancer origins. Also, exosomes derived from stem cells and tumor‐associated macrophages will be discussed in this regard. Finally, we will discuss the novel therapeutic strategies of exosomes as drug delivery vehicles against angiogenesis.
Vitexin suppresses RANKL‐induced osteoclastogenesis and prevents lipopolysaccharide (LPS)‐induced osteolysis
Authors: Jiang Jiawei , Jia Yewei , Lu Xuanyuan , Zhang Tan , Zhao Kangxian , Fu Ziyuan , Pang Cong , Qian Yu 
Published: February 2019

AbstractOsteolytic diseases are characterized by an increase in the number and/or activity of bone‐resorbing osteoclasts. Identification of natural compounds that can suppress osteoclast formation and function is crucial for the prevention and treatment of osteolytic diseases. Vitexin, a naturally‐derived flavonoid extracted from various medicinal plant species, demonstrates a broad range of pharmacological properties including anticancer and anti‐inflammatory effects. Here in this study, we showed that vitexin exerts antiosteoclastogenic effects by directly inhibiting receptor activator of nuclear factor‐κB ligand (RANKL)‐induced osteoclast formation and bone resorption in vitro and protected against lipopolysaccharide (LPS)‐induced inflammatory osteolysis in vivo. Vitexin suppressed the early activation of ERK and p38 MAPK pathways in response to RANKL thereby attenuating the downstream induction of c‐Fos and NFATc1, and abrogating the expression of osteoclast marker genes. Collectively, these results provide evidence for the therapeutic application of vitexin in the treatment of osteoclast‐mediated bone lytic diseases.
FOXE1 supports the tumor promotion of Gli2 on papillary thyroid carcinoma by the Wnt/β‐catenin pathway
Authors: Ma Jiancang , Huang Xin , Li Zongyu , Shen Yawei , Lai Jingyue , Su Qinghua , Zhao Jun , Xu Jinkai 
Published: February 2019

AbstractPapillary thyroid carcinoma (PTC) is a common malignancy in thyroid tissue. However, the molecular mechanism of PTC tumor progression remains unknown. The hedgehog (Hh) pathway is thought to play a key role during PTC development. Here we investigate the effects of glioma‐associated oncogene protein‐2 (Gli2), an important transcription factor of the Hh‐signaling pathway, on PTC. Gli2 and forkhead box E1 (FOXE1) protein levels were upregulated in tissues of PTC patients and PTC cell lines. Using the PTC cell line TPC‐1, we show that Gli2 small interfering RNA (siRNA) reduces cell proliferation, migration, and invasion; whereas overexpression of FOXE1 produces the opposite effects. Moreover, Gli2 siRNA inhibited the expression of genes implicated in the Wnt/β‐catenin pathway and that FOXE1 overexpression produces the opposite effects. Thus, it was indicated that Gli2 promoted the proliferation, migration, and invasion of TPC‐1 cells by activating Wnt/β‐catenin and FOXE1 is involved in this process. Xenograft models of PTC were also constructed, the results showed that Gli2 siRNA reduced the rate of tumor growth, FOXE1 levels, and the expression of the Wnt/β‐catenin pathway but FOXE1 overexpression reversed that effects. In conclusion, this study demonstrates that Gli2 promotes the growth of PTC tumors and TPC‐1 cell proliferation, migration, and invasion by activating the Wnt/β‐catenin pathway via FOXE1.
Susceptibility‐weighted imaging in malignant melanoma brain metastasis
Authors: Schwarz Daniel , Niederle Thomas , Münch Philipp , Hielscher Thomas , Hassel Jessica C. , Schlemmer Heinz‐Peter , Platten Michael , Winkler Frank , Wick Wolfgang , Heiland Sabine , Delorme Stefan , Bendszus Martin , Bäumer Philipp , Breckwoldt Michael O. 
Published: February 2019

BackgroundThe value of cerebral susceptibility‐weighted imaging (SWI) in malignant melanoma (MM) patients remains controversial and the effect of melanin on SWI is not well understood.PurposeTo systematically analyze the spectrum of intracerebral findings in MM brain metastases (BM) on SWI and to determine the diagnostic value of SWI.Study TypeRetrospective.Population/SubjectsIn all, 100 patients with melanoma BM (69 having received radiotherapy [RT] and 31 RT‐naïve) and a control group of 100 melanoma patients without BM were included. For detailed analysis of signal characteristics, 175 metastases were studied.Field Strength/SequenceGradient echo SWI sequence at 1.5, 3.0, and 9.4 T.AssessmentSignal characteristics from melanotic and amelanotic BMs on SWI with a focus on blooming artifacts were analyzed, as well as the presence and longitudinal dynamics of isolated SWI blooming artifacts in patients with and without BM.Statistical TestsChi‐squared and Student's t‐test were used for contingency table measures and group data of signal and clinical characteristics, respectively.ResultsMelanotic and amelanotic metastases did not show significant differences of SWI blooming artifacts (38% vs. 43%, P = 0.61). Most metastases without an initial SWI artifact developed a signal dropout during follow‐up (80%; 65/81). Isolated SWI artifacts were detected more frequently in patients with BM (20 vs. 9, P = 0.03), of which the majority were found in patients who had received RT (17 vs. 3, P = 0.08). None of these isolated SWI blooming artifacts turned into overt metastases over time (median follow‐up: 8.5 months). Similar findings persisted as remnants of successfully treated metastases (88%; 7/8).Data ConclusionWe conclude that SWI provides little additional diagnostic benefit over standard T1‐weighted imaging, as melanin content alone does not cause diagnostically relevant SWI blooming. Signal transition of SWI may rather indicate secondary phenomena like microbleeding and/or metal scavenging. Our results suggest that isolated SWI artifacts do not constitute vital tumor tissue but represent unspecific microbleedings, RT‐related parenchymal changes or posttherapeutic remnants of former metastatic lesions.Level of Evidence: 3Technical Efficacy Stage: 5J. Magn. Reson. Imaging 2019;50:1251–1259.
In vitro injection of osteoporotic cadaveric femurs with a triphasic calcium‐based implant confers immediate biomechanical integrity
Authors: Stroncek John D. , Shaul Jonathan L. , Favell Dominique , Hill Ronald S. , Huber Bryan M. , Howe James G. , Bouxsein Mary L. 
Published: February 2019

ABSTRACTCurrent pharmaceutical therapies can reduce hip fractures by up to 50%, but compliance to treatment is low and therapies take up to 18 months to reduce risk. Thus, alternative or complementary approaches to reduce the risk of hip fracture are needed. The AGN1 local osteo‐enhancement procedure (LOEP) is one such alternative approach, as it is designed to locally replace bone lost due to osteoporosis and provide immediate biomechanical benefit. This in vitro study evaluated the initial biomechanical impact of this treatment on human cadaveric femurs. We obtained 45 pairs of cadaveric femurs from women aged 77.8 ± 8.8 years. One femur of each pair was treated, while the contralateral femur served as an untreated control. Treatment included debridement, irrigation/suction, and injection of a triphasic calcium‐based implant (AGN1). Mechanical testing of the femora was performed in a sideways fall configuration 24 h after treatment. Of the 45 pairs, 4 had normal, 16 osteopenic, and 25 osteoporotic BMD T‐scores. Altogether, treatment increased failure load on average by 20.5% (p < 0.0001). In the subset of osteoporotic femurs, treatment increased failure load by 26% and work to failure by 45% (p < 0.01 for both). Treatment did not significantly affect stiffness in any group. These findings provide evidence that local delivery of the triphasic calcium‐based implant in the proximal femur is technically feasible and provides immediate biomechanical benefit. Our results provide strong rationale for additional studies investigating the utility of this approach for reducing the risk of hip fracture. © 2019 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society.
High performance LPF with negligible group delay using circular resonator and transfer function analysis
Authors: Rahmatinezhad Seyedeh Mitra , Makki Seyed Vahab Al‐Din , Mousavi Seyed Mohammad Hadi 
Published: February 2019

AbstractUsing circular and rectangular resonators, a new design of a compact microstrip lowpass filter (LPF) with negligible losses is proposed and fabricated. The proposed LPF has a 3 dB cut‐off frequency at 1.375 GHz with an adjusting range of 14.5%; moreover, the suggested configuration leads to a competitive roll‐off rate of 189 dB/ GHz and a negligible group delay of 0.47 ns. Attenuator cells have capability to produce numerous transmission zeros (TZs) at high frequencies; consequently, an ultra‐wide stopband (14 fc) with high suppression level (25 dB) is successfully obtained. Furthermore, the LPF has a small size of 0.067λg × 0.134λg (λg is the guided wavelength at 1.375 GHz). The transfer function is also calculated to adjust the location of the main TZs and the cut‐off frequency. Finally, an acceptable similarity between the simulated results and the tested ones verifies the simulation results.
A new toroidal metamaterial phase shifter
Authors: Shafaee Meisam , Razavi Seyed Mohammad Javad , Hamidi Emad 
Published: February 2019

AbstractIn this paper, the design of a rectangular waveguide metamaterial (MTM) phase shifter will be introduced in X band. The main disadvantages of the class of waveguide MTM phase shifters include high insertion loss (about 10 dB) and high DC magnetic bias field requirement (6‐7 kOe), that treated in the proposed phase shifter scheme by using toroidal shape ferrite core in conjunction with metalized parallel microstrip lines and implementing the multi‐section matching network, that leads to 3.2 dB insertion loss and a simple bias mechanism such as conventional toroidal phase shifter without consisting any high reluctance air‐gap, which could be implemented by no need of any feather coil system or higher current values. The results of simultaneous ENG and MNG design procedure for 288° differential phase shift with the 2 cm ferrite core length, shows 4 times compactness of proposed phase shifter in comparison with conventional toroidal phase shifter.
Disruption of O‐GlcNAc homeostasis during mammalian oocyte meiotic maturation impacts fertilization
Authors: Zhou Luhan T. , Romar Raquel , Pavone Mary Ellen , Soriano‐Úbeda Cristina , Zhang John , Slawson Chad , Duncan Francesca E. 
Published: February 2019

AbstractMeiotic maturation and fertilization are metabolically demanding processes, and thus the mammalian oocyte is highly susceptible to changes in nutrient availability. O‐GlcNAcylation—the addition of a single sugar residue (O‐linked β‐N‐acetylglucosamine) on proteins—is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins. O‐GlcNAcylation is mediated by O‐GlcNAc transferase (OGT), which adds O‐GlcNAc onto proteins, and O‐GlcNAcase (OGA), which removes it. Here we investigated O‐GlcNAcylation dynamics in bovine and human oocytes during meiosis and determined the developmental sequelae of its perturbation. OGA, OGT, and multiple O‐GlcNAcylated proteins were expressed in bovine cumulus oocyte complexes (COCs), and they were localized throughout the gamete but were also enriched at specific subcellular sites. O‐GlcNAcylated proteins were concentrated at the nuclear envelope at prophase I, OGA at the cortex throughout meiosis, and OGT at the meiotic spindles. These expression patterns were evolutionarily conserved in human oocytes. To examine O‐GlcNAc function, we disrupted O‐GlcNAc cycling during meiotic maturation in bovine COCs using Thiamet‐G (TMG), a highly selective OGA inhibitor. Although TMG resulted in a dramatic increase in O‐GlcNAcylated substrates in both cumulus cells and the oocyte, there was no effect on cumulus expansion or meiotic progression. However, zygote development was significantly compromised following in vitro fertilization of COCs matured in TMG due to the effects on sperm penetration, sperm head decondensation, and pronuclear formation. Thus, proper O‐GlcNAc homeostasis during meiotic maturation is important for fertilization and pronuclear stage development.
Outcomes in the elderly patient following enhanced recovery pathways for elective lower‐limb arthroplasty surgery
Authors: U Edmond Chun Ying , Starks Ian 
Published: February 2019

AbstractIntroductionEnhanced recovery pathways (ERPs) have been shown to reduce both morbidity and mortality, as well as length of stay, in very elderly patients undergoing joint replacement surgery. However, their impact on patient‐reported outcome measures (PROMs) in this vulnerable cohort of patients has not previously been investigated.MethodsOxford Hip and Knee Scores were collected pre‐ and postoperatively for patients undergoing joint replacement surgery at Wrexham Maelor Hospital, along with data on patient demographics.ResultsOf the 646 who had total hip replacements, 32 (4.95%) were aged 85 years or over, and of the 875 who had total knee replacements, 39 (4.46%) were aged 85 years or over. Similarly to younger patients, those over the age of 85 years saw a benefit in the outcome at 6 months and 24 months following elective hip and knee arthroplasty on an ERP. This was reflected by a significant increase in the outcome scores at 6 months postoperatively in both age groups undergoing either a total hip replacement or total knee replacement.ConclusionsWe found no detrimental effect of ERPs on PROMs data in older patients. In fact, these patients saw a similar benefit in outcome following elective hip and knee arthroplasty as the younger cohort.
Exposure to phthalate‐containing prescription drugs and the risk of colorectal adenocarcinoma: A Danish nationwide case‐control study
Authors: Ennis Zandra Nymand , Pottegård Anton , Ahern Thomas Patrick , Hallas Jesper , Damkier Per 
Published: February 2019

AbstractPurposeSome drug products contain phthalates as excipients, and in vitro studies have demonstrated that phthalates interfere with cellular mechanisms involved in colorectal cancer development. We therefore examined the association between cumulative phthalate exposure from drug products and risk of colorectal adenocarcinomas.MethodsWe used the Danish Cancer Registry to identify all patients with incident colorectal adenocarcinoma from 2008 to 2015 (n = 25 814). Each cancer case was matched to ten population controls. Linking information from Danish registers, we quantified cumulative phthalate exposure to the ortho‐phthalates diethyl phthalate (DEP) and dibutyl phthalate (DBP) as well as enteric phthalate polymers from orally administered drugs. The association between cumulative phthalate exposure and colorectal cancer was estimated using conditional logistic regression.ResultsCumulative exposure to ortho‐phthalates exceeding 500 mg was associated with lower odds of colorectal cancer diagnosis (ORadj = 0.89; 95% CI, 0.81‐0.96). Similar associations were observed for all DEP exposure exceeding 500 mg. Subgroup analysis excluding NSAID users, demonstrated that ortho‐phthalate exposure was positively associated with colorectal cancer (ORadj = 1.26; 95% CI, 1.05‐1.51).ConclusionWe found an apparent overall protective effect of cumulative phthalate exposure from drug excipients for colorectal adenocarcinoma. Omitting NSAID users reversed the signal and suggested a slightly increased risk associated with high cumulative ortho‐phthalate exposure.
Modelling and forecasting PV production in the absence of behind‐the‐meter measurements
Authors: Landelius Tomas , Andersson Sandra , Abrahamsson Roger 
Published: February 2019

AbstractThis paper deals with hourly day‐ahead prediction of the net electricity load at nine photovoltaic installations in a Swedish regional electricity network. The objective of the study was to develop, test, and evaluate a set of methods to predict the contribution of PV power to the grid without knowing the production and consumption “behind‐the‐meter.” An indirect and a direct approach for prediction of the net load were evaluated. For the indirect approach, a model of the gross production was first estimated based on the open‐source software PVLIB. The model was then used to predict the net load given a forecast of the gross consumption. Since we lacked a model of the latter, we used a “perfect forecast,” in terms of measured gross consumption, to estimate the performance of this approach. In the direct approach, a model of the net load was estimated using either linear regression or an artificial neural network. Here, the model was used for prediction of the net load without any information about the gross consumption. Both approaches rely on information from a numerical weather prediction model together with net load measurements from the previous day. Forecasts using the indirect approach with perfect information about the gross consumption resulted in a normalized (with installed nominal power) RMSEn of 11%. The direct approach with the artificial neural network also resulted in an RMSEn of 11%, even though it did not have any information from behind the meter. Linear regression had an RMSEn of 12%.
Protein Composition Reflects Extracellular Vesicle Heterogeneity
Authors: Vagner Tatyana , Chin Andrew , Mariscal Javier , Bannykh Serguei , Engman David M. , Di Vizio Dolores 
Published: February 2019

AbstractExtracellular vesicles (EVs) are membrane‐enclosed particles that are released by virtually all cells from all living organisms. EVs shuttle biologically active cargo including protein, RNA, and DNA between cells. When shed by cancer cells, they function as potent intercellular messangers with important functional consequences. Cells produce a diverse spectrum of EVs, spanning from small vesicles of 40–150 nm in diameter, to large vesicles up to 10 μm in diameter. While this diversity was initially considered to be purely based on size, it is becoming evident that different classes of EVs, and different populations within one EV class may harbor distinct molecular cargo and play specific functions. Furthermore, there are considerable cell type‐dependent differences in the cargo and function of shed EVs. This review focuses on the most recent proteomic studies that have attempted to capture the EV heterogeneity by directly comparing the protein composition of different EV classes and EV populations derived from the same cell source. Recent studies comparing protein composition of the same EV class(es) derived from different cell types are also summarized. Emerging approaches to study EV heterogeneity and their important implications for future studies are also discussed.