bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dysregulated N6‐methyladenosine methylation writer METTL3 contributes to the proliferation and migration of gastric cancer
Authors: Liu Tong , Yang Sheng , Sui Jing , Xu Si‐Yi , Cheng Yan‐ping , Shen Bo , Zhang Yan , Zhang Xiao‐mei , Yin Li‐hong , Pu Yue‐pu , Liang Ge‐yu 
Published: June 2019

AbstractAccumulating evidence implies that N6‐methyladenosine (m6A) methylation participated in the tumorigenesis of gastric cancer (GC). Here we synthetically analyzing the prognostic value and expression profile of seven m6A methylation‐relevant genes through silico analysis of sequencing data downloaded from The Cancer Genome Atlas, Kaplan–Meier plotter, and Gene Expression Omnibus database. We explored the methyltransferase‐like 3 (METTL3) expression in GC cell line and tumor tissues by reverse transcription quantitative polymerase chain reaction and western blot analysis. The m6A methylation status of total RNA was measured by m6A RNA methylation quantification kit. Small interfering RNA was used to establish METTL3 knockdown cell lines. We also measure the proliferation and migration capability GC cell. Furthermore, we detect the epithelial cell mesenchymal transition marker and m6A methylation level after METTL3 knock down. Our result revealed that METTL3 was significantly increased in GC tissues compared with control in big crowd data sets. Survival analysis showed that METTL3 serve as a poor prognostic factor for GC patients. The expression level of METTL3 gradually increased with the progress of tumor stage and grade. GFI1 is an important transcription factor associated with METTL3. We verified the up‐trend of METTL3 in messenger RNA and protein expression and observed a significant increase in the m6A methylation status of total RNA in the GC cells and tissues. METTL3 knockdown inhibited total RNA m6A methylation level, as well as cell proliferation and migration capacity. Moreover, METTL3 knockdown decreased α‐smooth muscle actin. Taken together, our finding revealed that m6A methylation writer METTL3 serve as an oncogene in tumorigenesis of GC.
DJ‐1 regulates tyrosine hydroxylase expression through CaMKKβ/CaMKIV/CREB1 pathway in vitro and in vivo
Authors: Xu Xingyun , Wang Rui , Hao Zongbing , Wang Guanghui , Mu Chenchen , Ding Jianqing , Sun Wanping , Ren Haigang 
Published: June 2019

AbstractLack of dopamine production and neurodegeneration of dopaminergic neurons in the substantia nigra are considered as the major characteristics of Parkinson's disease, a prevalent movement disorder worldwide. DJ‐1 mutation leading to loss of its protein functions is a genetic factor of PD. In this study, our results illustrated that DJ‐1 can directly interact with Ca2+/calmodulin‐dependent protein kinase kinase β (CaMKKβ) and modifies the cAMP‐responsive element binding protein 1 (CREB1) activity, thus regulates tyrosine hydroxylase (TH) expression. In Dj‐1 knockout mouse substantia nigra, the levels of TH and the phosphorylation of CREB1 Ser133 are significantly decreased. Moreover, Dj‐1 deficiency suppresses the phosphorylation of CaMKIV (Thr196/200) and CREB1 (Ser133), subsequently inhibits TH expression in vitro. Furthermore, Knockdown of Creb1 abolishes the effects of DJ‐1 on TH regulation. Our data reveal a novel pathway in which DJ‐1 regulates CaMKKβ/CaMKIV/CREB1 activities to facilitate TH expression.
Characterization and tentative identification of new flunitrazepam metabolites in authentic human urine specimens using liquid chromatography‐Q exactive‐HF hybrid quadrupole‐Orbitrap‐mass spectrometry (LC‐QE‐HF‐MS)
Authors: Qin Shiyang , Xin Guobin , Wang Yuanfeng , Qiao Jing , Zhang Wenfang , Xu Duoqi , Xu Zizhen , Liu Yongtao , Zhang Ying , Lu Jianghai 
Published: June 2019

AbstractFlunitrazepam (FNZ) is a potent hypnotic, sedative, and amnestic drug used to treat severe insomnia. In our recent study, FNZ metabolic profiles were investigated carefully. Six authentic human urine samples were purified using solid phase extraction (SPE) without enzymatic hydrolysis, and urine extracts were then analyzed by liquid chromatography‐Q exactive‐HF hybrid quadrupole‐Orbitrap‐mass spectrometry (LC‐QE‐HF‐MS), using the full scan positive ion mode and targeted MS/MS (ddms2) technique to make accurate mass measurements. There were 25 metabolites, including 13 phase I and 12 phase II metabolites, which were detected and tentatively identified by LC‐QE‐HF‐MS. In addition, nine previously unreported phase II glucuronide conjugates and four phase I metabolites are reported here for the first time. Eight metabolic pathways, including N‐reduction and O‐reduction, N‐glucuronidation, O‐glucuronidation, mono‐hydroxylation and di‐hydroxylation, demethylation, acetylation, and combinations, were implicated in this work, and 2‐O‐reduction together with dihydroxylation were two novel metabolic pathways for FNZ that were identified tentatively. Although 7‐amino FNZ is widely considered to be the primary metabolite, a previously unreported metabolites (M12) can also serve as a potential biomarker for FNZ misuse.
Exploring two contrasting surface‐active exopolysaccharides from a single strain of Ochrobactrum utilizing different hydrocarbon substrates
Authors: Sengupta Dipanjan , Datta Sriparna , Biswas Dipa 
Published: June 2019

AbstractDuring production and characterization of exopolysaccharides (EPS) of Ochrobactrum pseudintermedium C1, it was observed that an experimental change in the basic hydrocarbon type of substrate for bacterial utilization led to elicitation of different surface‐active properties in the EPS produced. In the sugar substrate, it elicited surfactant property, while in oil substrates it elicited emulsifying property, which indicated that the EPS might be different. Consequently, attention was focused on a detailed analysis of this substrate‐specific EPS. Utilizing waste sugar, edible, and mineral oil substrates, EPS produced in each situation was characterized. Besides estimating surface activity and thermostability, each substrate‐specific EPS was analyzed by Fourier‐transform infrared spectroscopy, gas chromatography‐mass spectroscopy, 1H‐nuclear magnetic resonance, and matrix‐assisted laser desorption/ionization—time of flight mass spectroscopy to find any structural difference. The results were significantly contrasting although the similarity in molecular mass suggested a basic similarity in polysaccharide structure. Morphological differences were also evident both macroscopically and microscopically with scanning electron microscopy. As the surface‐active property of EPS was dependent on the substrate utilized, their structural differences might account for it. These diverse surface activities of EPS produced by a single bacterial strain simply by changing the nature of substrate would also augment their bioapplications. Moreover, utilization of waste and easily available substrates should make such applications convenient, ecofriendly, and cost‐worthy.
Non‐Invasive Ultrasound Quantification of Scar Tissue Volume Identifies Early Functional Changes During Tendon Healing
Authors: Ackerman Jessica E. , Studentsova Valentina , Myers Marlin , Buckley Mark R. , Richards Michael S. , Loiselle Alayna E. 
Published: June 2019

ABSTRACTTendon injuries are very common and disrupt the transmission of forces from muscle to bone, leading to impaired function and quality of life. Successful restoration of tendon function after injury is a challenging clinical problem due to the pathological, scar‐mediated manner in which the tendons heal. Currently, there are no standard treatments to modulate scar tissue formation and improve tendon healing. A major limitation to the identification of therapeutic candidates has been the reliance on terminal endpoint metrics of healing in pre‐clinical studies, which require a large number of animals and result in destruction of the tissue. To address this limitation, we have identified quantification of scar tissue volume (STV) from ultrasound (US) imaging as a longitudinal, non‐invasive metric of tendon healing. STV was strongly correlated with established endpoint metrics of gliding function including gliding resistance and metatarsophalangeal (MTP) flexion angle. However, no associations were observed between STV and structural or material properties. To define the sensitivity of STV to identify differences between functionally discrete tendon healing phenotypes, we utilized S100a4 haploinsufficient mice (S100a4GFP/+), which heal with improved gliding function relative to wild‐type (WT) littermates. A significant decrease in STV was observed in S100a4GFP/+ repairs, relative to WT at day 14. Taken together, these data suggest US quantification of STV as a means to facilitate the rapid screening of biological and pharmacological interventions to improve tendon healing, and identify promising therapeutic targets, in an efficient, cost‐effective manner. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2476–2485, 2019
Plasma Citrulline Concentrations in Neonates With or Without Gastrointestinal Disease During Periods of Parenteral and Enteral Nutrition
Authors: Herrera Oscar R. , Talati Ajay J. , Helms Richard A. 
Published: June 2019

AbstractIntroductionCitrulline is synthesized primarily in enterocytes. Retrospective work revealed higher plasma concentrations in patients without gastrointestinal (GI) disease than in those with GI disease, regardless of bowel resection, leading us to speculate whether it could be used as a marker of gut function prospectively. Our purpose was to analyze plasma citrulline in these patients, comparing a period of exclusive parenteral nutrition (PN) vs both PN and enteral nutrition (PN/EN).MethodsPremature neonates were included in this study. Plasma samples were collected during 2 periods, PN and PN/EN. They were classified into groups: patients without GI disease (Group 1), patients with GI disease without resection (Group 2), and patients with GI disease and resection (Group 3). Plasma was analyzed by high‐performance liquid chromatography and tandem mass spectrometry (LC‐MS/MS). Data were described as median with ranges.ResultsFifty patients were recruited for this study, from which 164 samples were obtained and analyzed by LC‐MS. Median plasma citrulline concentrations were 12.3 (5.6–39.4) µmol/L, 14.9 (6.8–39.8) µmol/L, and 10.8 (2.0–23.6) µmol/L for Groups 1, 2, and 3, respectively. After Bonferroni correction, only Group 3 had a significantly different median from the others. No differences were observed within periods of nutrition (PN vs PN/EN). Postconceptual age (PCA), among others, was assessed to determine differences for which the former demonstrated significance.ConclusionPremature neonates with bowel resection had lower plasma citrulline concentrations, confirming its role as gut mass marker, though without differences during transitional feeding. PCA may affect expression of this protein.
Changes in the extent and distribution of urban land cover in the Democratic People's Republic of Korea (North Korea) between 1987 and 2010
Authors: Kang Sangjun , Choi Jinmu , Yoon Hyejin , Choi Woonsup 
Published: June 2019

AbstractLargely due to data unavailability, the spatial pattern of urban growth in North Korea has been rarely studied. This study explored urban changes in North Korea and provided their plausible causes. The present study used satellite‐based land cover data sets produced by the government of South Korea to examine the extent and distribution of urban land cover in North Korea between the late 1980s (1987–1989) and late 2000s (2008–2010) at the municipal level. The urban expansion intensity index (UEII) was calculated for two 10‐year intervals, and the spatial autocorrelation of UEII values was examined. Major findings from the study are summarized as follows: (a) the capital city Pyongyang's dominance continued without any obvious sign of slowing down, (b) economic development districts do not appear to have much influence on urban land cover changes, and (c) the extent of urban land cover slightly decreased in much of the country between the late 1990s (1997–1999) and late 2000s (2008–2010). The results and discussion in this study suggest internal migration and stagnant economy as probably important causes for the phenomena.
Robust pCASL perfusion imaging using a 3D Cartesian acquisition with spiral profile reordering (CASPR)
Authors: Greer Joshua S. , Wang Xinzeng , Wang Yiming , Pinho Marco C. , Maldjian Joseph A. , Pedrosa Ivan , Madhuranthakam Ananth J. 
Published: June 2019

PurposeTo improve the robustness of arterial spin‐labeled measured perfusion using a novel Cartesian acquisition with spiral profile reordering (CASPR) 3D turbo spin echo (TSE) in the brain and kidneys.MethodsThe CASPR view ordering followed a pseudo‐spiral trajectory on a Cartesian grid, by sampling the center of k‐space at the beginning of each echo train of a segmented 3D TSE acquisition. With institutional review board approval and written informed consent, 14 normal subjects (9 brain and 5 kidneys) were scanned with pCASL perfusion imaging using 3D CASPR and compared against 3D linear TSE (brain and kidneys), the established 2D EPI and 3D gradient and spin echo perfusion (brain), and 2D single‐shot turbo spin‐echo perfusion (kidneys). The SNR and the quantitative perfusion values were compared among different acquisitions.Results3D CASPR TSE achieved robust perfusion across all slices compared to 3D linear TSE in the brain and kidneys. Compared to 2D EPI, 3D CASPR TSE showed higher SNR across the brain (P < 0.01), and exhibited good agreement (36.4 ± 4.7 and 36.9 ± 5.3 mL/100 g/min with 2D EPI and 3D CASPR, respectively), and with 3D gradient and spin echo (27.9 ± 7.2 mL/100 g/min). Compared to a single slice 2D single‐shot turbo spin‐echo acquisition, 3D CASPR TSE achieved robust perfusion across the entire kidneys in similar scan time with comparable quantified perfusion values (154.1 ± 74.6 and 151.7 ± 70.6 mL/100 g/min with 2D single‐shot turbo spin‐echo and 3D CASPR, respectively).ConclusionThe CASPR view ordering with 3D TSE achieves robust arterial spin‐labeled perfusion in the brain and kidneys because of the sampling of the center of k‐space at the beginning of each echo train.
Numerical modeling of rock failure under dynamic loading with polygonal elements
Authors: Saksala Timo , Jabareen Mahmood 
Published: June 2019

SummaryPolygonal finite elements are gaining an increasing attention in the computational mechanics literature, but their application in rock mechanics is very rare. This paper deals with numerical modeling of rock failure under dynamic loading based on polygonal finite elements. For this end, a damage‐viscoplastic constitutive model for rock based on the Mohr‐Coulomb criterion with the Rankine criterion as a tensile cutoff is employed and implemented with the polygonal finite element method. Moreover, the mineral mesostructure or rock is described by randomly mapping groups of polygonal elements representing the constituent minerals into a global mesh and assigning these groups with the corresponding mineral material properties. The performance of the polygonal elements is compared with that of the linear and quadratic triangular and bilinear quadrilateral elements in numerical simulations of controlled shear band formation under uniaxial compression and lateral splitting failure in the dogbone tension test. Numerical simulations of uniaxial tension and compression tests as well as dynamic Brazilian disc test under increasing loading rates demonstrate that the present approach predicts the correct failure modes as well as the dynamic increase in strength of rock.
Development of Obesity Competencies for Medical Education: A Report from the Obesity Medicine Education Collaborative
Authors: Kushner Robert F. , Horn Deborah B. , Butsch W. Scott , Brown Joshua D. , Duncan Katherine , Fugate Colony S. , Gorney Carol , Grunvald Eduardo L. , Igel Leon I. , Pasarica Magdalena , Pennings Nicholas , Soleymani Taraneh , Velazquez Amanda 
Published: June 2019

ObjectiveObesity Medicine Education Collaborative (OMEC) was formed to develop obesity‐focused competencies and benchmarks that can be used by undergraduate and graduate medical education program directors. This article describes the developmental process used to create the competencies.MethodsFifteen professional organizations with an interest in obesity collaborated to form OMEC. Using the six Core Competencies of the Accreditation Council for Graduate Medical Education as domains and as a guiding framework, a total of 36 group members collaborated by in‐person meetings, email exchange, and conference calls. An iterative process was used by each working subgroup to develop the competencies and assessment benchmarks. The initial work was subsequently externally reviewed by 19 professional organizations.ResultsThirty‐two competencies were developed across the six domains. Each competency contains five descriptive measurement benchmarks for evaluator rating.ConclusionsThis set of OMEC obesity‐focused competencies is the first evaluation tool developed to be used within undergraduate and graduate medical training programs for both formative and summative assessments. Routine and more robust assessment is expected to increase the competence of health care providers to assess, prevent, and treat obesity. In addition to dissemination, the competencies and benchmarks will need to undergo evaluation for further validity and practicality.
Maternal BMI‐Increasing Genetic Risk Score and Fetal Weights among Diverse US Ethnic Groups
Authors: Shrestha Deepika , Rahman Mohammad L. , Hinkle Stefanie N. , Workalemahu Tsegaselassie , Tekola‐Ayele Fasil 
Published: June 2019

ObjectiveAssociations between maternal genetic risk for obesity and fetal weight were examined at the end of the first (13 weeks 6 days), second (27 weeks 6 days), and third (40 weeks 0 days) trimesters of pregnancy among four race/ethnic groups in the US.MethodsFor 603 white, 591 black, 535 Hispanic, and 216 Asian women, maternal genetic risk score (GRS) was calculated as the sum of 189 BMI‐increasing alleles and was categorized into high or low GRS. Associations between GRS (continuous and categorical) and estimated fetal weight were tested overall and stratified by prepregnancy BMI, gestational weight gain (GWG), and fetal sex.ResultsHigh GRS compared with low GRS was associated with increased fetal weight at the end of the second (β: 22.7 g; 95% CI: 2.4‐43.1; P = 0.03) and third trimesters (β: 88.3 g; 95% CI: 9.0‐167.6; P = 0.03) among Hispanic women. The effect of GRS was stronger among Hispanic women with normal prepregnancy weight, adequate first trimester GWG, or inadequate second trimester GWG (P < 0.05). Among Asian women, high GRS was associated with increased weight among male fetuses but decreased weight among female fetuses (P < 0.05).ConclusionsMaternal obesity genetic risk was associated with fetal weight with potential effect modifications by maternal prepregnancy BMI, GWG, and fetal sex.
Molecular pathology of the luminal class of urothelial tumors
Authors: Bernardo Carina , Eriksson Pontus , Marzouka Nour‐al‐dain , Liedberg Fredrik , Sjödahl Gottfrid , Höglund Mattias 
Published: June 2019

AbstractMolecular subtypes of urothelial carcinoma may be divided into luminal and nonluminal tumors. Nonluminal tumors are composed of cases with basal/squamous‐like or small cell/neuroendocrine features, with a consensus on the molecular characteristics of the respective subtype. In contrast, luminal tumors are more disparate with three to five suggested subtypes and with definitions that do not always cohere. To resolve some of these disparities we assembled a cohort of 344 luminal tumors classified as urothelial‐like (Uro), with the subtypes UroA, UroAp, UroB, and UroC, or genomically unstable (GU) according to the LundTax system. Cases were systematically analyzed by immunohistochemistry using antibodies for proteins representing important biological processes or cellular states: KRT5, EGFR, and CDH3 for the integrity of a basal cell layer; CCNB1, Ki67, and FOXM1 for proliferation; FGFR3 and ERBB2 for receptor tyrosine kinase status; CCND1, CDKN2A(p16), RB1, and E2F3 for cell cycle regulation; PPARG, GATA3, and TP63 for the differentiation regulatory system; and KRT20 and UPK3 for the differentiation readout. We show that Uro tumors form one, albeit heterogenous, group characterized by FGFR3, CCND1, and RB1 expression, but low or absence of CDKN2A(p16) and ERBB2 expression. The opposite expression pattern is observed in GU cases. Furthermore, Uro tumors are distinguished from GU tumors by showing a high RB1/p16 expression ratio. Class defining characteristics were independent of pathological stage and growth pattern, and thus intrinsic. In Uro tumors, proliferation was limited to a well‐defined single layer of basal‐like cells in UroA tumors but occurred throughout the tumor parenchyma, independent of the basal layer, in the more progressed UroAp and UroC tumors. A similar change in proliferation topology was not observed in GU. We conclude that luminal urothelial carcinomas consist, at the molecular pathology level, of two major subtypes, the larger heterogenous Uro and the biologically distinct GU subtype. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Upregulation of the Glutaminase II Pathway Contributes to Glutamate Production upon Glutaminase 1 Inhibition in Pancreatic Cancer
Authors: Udupa Sunag , Nguyen Stephanie , Hoang Giang , Nguyen Tu , Quinones Addison , Pham Khoa , Asaka Ryoichi , Nguyen Kiet , Zhang Cissy , Elgogary Amira , Jung Jin G. , Xu Qingguo , Fu Jie , Thomas Ajit G. , Tsukamoto Takashi , Hanes Justin , Slusher Barbara S. , Cooper Arthur J. L. , Le Anne 
Published: June 2019

AbstractThe targeting of glutamine metabolism specifically via pharmacological inhibition of glutaminase 1 (GLS1) has been translated into clinical trials as a novel therapy for several cancers. The results, though encouraging, show room for improvement in terms of tumor reduction. In this study, the glutaminase II pathway is found to be upregulated for glutamate production upon GLS1 inhibition in pancreatic tumors. Moreover, genetic suppression of glutamine transaminase K (GTK), a key enzyme of the glutaminase II pathway, leads to the complete inhibition of pancreatic tumorigenesis in vivo unveiling GTK as a new metabolic target for cancer therapy. These results suggest that current trials using GLS1 inhibition as a therapeutic approach targeting glutamine metabolism in cancer should take into account the upregulation of other metabolic pathways that can lead to glutamate production; one such pathway is the glutaminase II pathway via GTK.
A density functional theory study on the superacidity of sulfuric, fluorosulfuric, and triflic acid derivatives with two cyclopentadiene rings: ion pairs formation in the gas phase
Authors: Valadbeigi Younes , Vianello Robert 
Published: June 2019

AbstractThe gas phase acidity of organosulfuric acid derivatives with two cyclopentadiene rings replacing the doubly‐bonded oxygen atoms was computationally assessed using the B3LYP DFT functional and 6–311++G(d,p) basis set. Introduced five‐membered rings increased the acidity through the delocalization of the excess negative charge in conjugates bases and by providing positions to accommodate electron withdrawing substituents such as F and CN. The calculated enthalpies of deprotonation (∆Hacid) of polycyanated systems were as low as 227.8 to 263.2 kcal mol–1 indicating exceptional superacidity. Substitution of one OH moiety by F or CF3 groups offered additional acidifying effect by preventing prototropic tautomerism in the neutral acids that acts towards lowering the acidity. The designed systems spontaneously protonated H2O and NH3 in the gas phase and produced stable ion pair clusters.