bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long noncoding RNA RMRP promotes proliferation and invasion via targeting miR‐1‐3p in non–small‐cell lung cancer
Authors: Wang Yi , Luo Xigang , Liu Yang , Han Guanying , Sun Dapeng 
Published: May 2019

AbstractThe long noncoding RNA component of mitochondrial RNA‐processing endoribonuclease (lncRNA RMRP) plays an important role in tumor development. In the present study, we determined the regulatory function of RMRP in non–small‐cell lung cancer (NSCLC). The NSCLC tissues and the adjacent nontumor tissues were collected for the study. The RMRP expression was detected by quantitative real time‐PCR in NSCLC and lung cancer cell lines. The functional validation experiments were performed to determine the role of RMRP on NSCLC progression. In addition, we identified the downstream target miRNAs for RMRP. The results showed that RMRP was elevated in NSCLC tissues and cell lines. High RMRP expression was closely associated with advanced stage for the clinical features and low overall survival in NSCLC patients. Functional assay showed that loss of RMRP markedly inhibited cell proliferation, migration, and invasion. Flow cytometry assay demonstrated that the inhibition of RMRP dramatically induced cell cycle arrest in the G0/G1 phase. Moreover, we found that the role of RMRP on NSCLC cell progression was modulated by the inhibition of miR‐1‐3p. Collectively, our results demonstrated that the “RMRP‐miR‐1‐3p” axis might promote NSCLC progression. Hence, these investigations will provide a therapeutic target and strategy for the treatment of NSCLC progression.
Genome‐wide microRNA screening reveals miR‐582‐5p as a mesenchymal stem cell‐specific microRNA in subchondral bone of the human knee joint
Authors: Wang Pinger , Dong Rui , Wang Baoli , Lou Zhaohuan , Ying Jun , Xia Chenjie , Hu Songfeng , Wang Weidong , Sun Qi , Zhang Peng , Ge Qinwen , Xiao Luwei , Chen Di , Tong Peijian , Li Ju , Jin Hongting 
Published: May 2019

AbstractEmerging evidence suggests that microRNAs (miRNAs) may be pathologically involved in osteoarthritis (OA). Subchondral bone (SCB) sclerosis is accounted for the knee osteoarthritis (KOA) development and progression. In this study, we aimed to screen the miRNA biomarkers of KOA and investigated whether these miRNAs regulate the differentiation potential of mesenchymal stem cells (MSCs) and thus contributing to SCB. We identified 48 miRNAs in the blood samples in KOA patients (n = 5) through microarray expression profiling detection. After validation with larger sample number, we confirmed hsa‐miR‐582‐5p and hsa‐miR‐424‐5p were associated with the pathology of SCB sclerosis. Target genes prediction and pathway analysis were implemented with online databases, indicating these two candidate miRNAs were closely related to the pathways of pluripotency of stem cells and pathology of OA. Surprisingly, mmu‐miR‐582‐5p (homology of hsa‐miR‐582‐5p) was downregulated in osteogenic differentiation and upregulated in adipogenic differentiation of mesenchymal progenitor C3H10T1/2 cells, whereas mmu‐mir‐322‐5p (homology of hsa‐miR‐424‐5p) showed no change through the in vitro study. Supplementing mmu‐miR‐582‐5p mimics blocked osteogenic and induced adipogenic differentiation of C3H10T1/2 cells, whereas silencing of the endogenous mmu‐miR‐582‐5p enhanced osteogenic and repressed adipogenic differentiation. Further mechanism studies showed that mmu‐miR‐582‐5p was directly targeted to Runx2. Mutation of putative mmu‐miR‐582‐5p binding sites in Runx2 3′ untranslated region (3′UTR) could abolish the response of the 3′UTR‐luciferase construct to mmu‐miR‐582‐5p supplementation. Generally speaking, our data suggest that miR‐582‐5p is an important biomarker of KOA and is able to regulate osteogenic and adipogenic differentiation of MSCs via targeting Runx2. The study also suggests that miR‐582‐5p may play a crucial role in SCB sclerosis of human KOA.
LncRNA LINC01857 promotes growth, migration, and invasion of glioma by modulating miR‐1281/TRIM65 axis
Authors: Hu Guozhang , Liu Naijie , Wang Han , Wang Yue , Guo Zhigang 
Published: May 2019

AbstractThe great importance of long noncoding RNAs (lncRNAs) has been acknowledged in tumorigenesis gradually. LncRNA LINC01857 is a novel lncRNA and has been reported to promote breast cancer progression. However, the biological roles of LINC01857 in glioma are not explored. In the present research, LINC01857 levels were found to be upregulated in glioma. In addition, LINC01857 expression is negatively correlated with survival rate in glioma patients. Functional investigation revealed that LINC01857 downregulation impaired glioma proliferation and invasiveness. Furthermore, LINC01857 knockdown led to repressed growth of glioma in vivo. We found that LINC01857 could be a sponge for miR‐1281 and inhibits its level to upregulate TRIM65 expression. What's more, we showed that miR‐1281 mimics also attenuated tumor cell proliferation, migration, and invasion. And rescue assays demonstrated that LINC01857 promotes glioma progression through modulating miR‐1281/TRIM65 pathway. Collectively, this study first demonstrated that a novel LINC01857/miR‐1281/TRIM65 signaling regulates glioma progression.
Design and construction of a recombinant lentiviral vector with specific tropism to human epidermal growth factor‐overexpressed cancer cells: Developing a new retargeting system for lentivirus vectors
Authors: Ebrahimabadi Sima , Shahbazi Majid , Akbari Mona , Golalipour Masoud , Farazmandfar Touraj 
Published: May 2019

AbstractBackgroundTargeting of specific tissues and cells by viruses is one of the challenges faced by researchers. Lentiviral vectors (LVs) are one of the most promising gene delivery systems in cancer gene therapy. Therefore, we aimed to design a novel lentiviral delivery system that expresses anti‐ human epidermal growth factor 2 (HER2) designed anykrin repeat protein (DARPin) on the vector envelope to create a pseudotyped lentivirus for targeting HER2‐positive cancer cells.MethodsA helper plasmid producing the viral vector envelope containing anti‐HER2 DARPin‐G3 was constructed. LV was produced by transfer vector containing green fluorescent protein (GFP) gene and helper plasmids in human embryonic kidney 293 cells. The human breast cancer cell lines SKBR3 (normal and with inhibited endocytosis) (HER2‐positive) and MDA‐MB‐231 (HER2‐negative) were transduced by the recombinant viral vector. The GFP‐based transduction rate was determined by flow cytometry and fluorescence microscopy.ResultsThe anti‐HER2 DARPin concentration in DARPin‐LVs was significantly higher than the envelope G glycoprotein of the vesicular stomatitis virus‐LVs (non‐anti‐HER2 control) (p < 0.0001). In flow cytometry assays, the percentage of transduction by recombinant LV was significantly higher in SKBR3 cells than in SKBR3 cells with inhibited endocytosis (p = 0.0074) and MDA‐MB‐231 cells (p = 0.0037). In fluorescence microscopy assays, the percentage of transduction by new LV was significantly higher in SKBR3 cells than in SKBR3 cells with inhibited endocytosis (p = 0.0026) and MDA‐MB‐231 cells (p = 0.0014).ConclusionsWe constructed a new recombinant LV with a defect in cell entry directly, containing an anti‐HER2 DARPin on the vector envelope with specific tropism to HER2 receptor on HER2‐positive cancer cells. We assumed that this viral vector transduces cells via an endocytosis‐dependent process.
Recognition and interaction of CphA from Aeromonas hydrophila with imipenem and biapenem by spectroscopic analysis in combination with molecular docking
Authors: Zhang Yeli , Bian Liujiao 
Published: May 2019

AbstractThe molecular recognition and interaction of CphA from Aeromonas hydrophila with imipenem (Imip) and biapenem (Biap) were studied by means of the combined use of fluorescence spectra and molecular docking. The results showed that both the fluorescence quenching of CphA by Imip and Biap were caused through the combined dynamic and static quenching, and the latter was dominating in the process; the microenvironment and conformational of CphA were altered upon the addition of Imip and Biap from synchronous and three‐dimensional fluorescence. The binding of CphA with Imip or Biap caused a conformational change in the loop of CphA, and through the conformational change, the loop opened the binding pocket of CphA to allow for an induced fit of the newly introduced ligand. In the binding of CphA with Imip, the whole molecule entered into the active pocket of CphA. The binding was driven by enthalpy change, and the binding force between them was mainly hydrogen bonding and Van der Waals force; whereas in the binding of CphA with Biap, only the beta‐lactam ring of Biap entered into the binding pocket of CphA while the side chain was located outside the active pocket. The binding was driven by the enthalpy change and entropy change together, and the binding force between them was mainly electrostatic interaction. This study provided an insight into the recognition and binding of CphA with antibiotics, which may be helpful for designing new substrate for beta‐lactamase and developing new antibiotics resistant to superbugs.
Deep learning enables automatic detection and segmentation of brain metastases on multisequence MRI
Authors: Grøvik Endre , Yi Darvin , Iv Michael , Tong Elizabeth , Rubin Daniel , Zaharchuk Greg 
Published: May 2019

BackgroundDetecting and segmenting brain metastases is a tedious and time‐consuming task for many radiologists, particularly with the growing use of multisequence 3D imaging.PurposeTo demonstrate automated detection and segmentation of brain metastases on multisequence MRI using a deep‐learning approach based on a fully convolution neural network (CNN).Study TypeRetrospective.PopulationIn all, 156 patients with brain metastases from several primary cancers were included.Field Strength1.5T and 3T. [Correction added on May 24, 2019, after first online publication: In the preceding sentence, the first field strength listed was corrected.]SequencePretherapy MR images included pre‐ and postgadolinium T1‐weighted 3D fast spin echo (CUBE), postgadolinium T1‐weighted 3D axial IR‐prepped FSPGR (BRAVO), and 3D CUBE fluid attenuated inversion recovery (FLAIR).AssessmentThe ground truth was established by manual delineation by two experienced neuroradiologists. CNN training/development was performed using 100 and 5 patients, respectively, with a 2.5D network based on a GoogLeNet architecture. The results were evaluated in 51 patients, equally separated into those with few (1–3), multiple (4–10), and many (>10) lesions.Statistical TestsNetwork performance was evaluated using precision, recall, Dice/F1 score, and receiver operating characteristic (ROC) curve statistics. For an optimal probability threshold, detection and segmentation performance was assessed on a per‐metastasis basis. The Wilcoxon rank sum test was used to test the differences between patient subgroups.ResultsThe area under the ROC curve (AUC), averaged across all patients, was 0.98 ± 0.04. The AUC in the subgroups was 0.99 ± 0.01, 0.97 ± 0.05, and 0.97 ± 0.03 for patients having 1–3, 4–10, and >10 metastases, respectively. Using an average optimal probability threshold determined by the development set, precision, recall, and Dice score were 0.79 ± 0.20, 0.53 ± 0.22, and 0.79 ± 0.12, respectively. At the same probability threshold, the network showed an average false‐positive rate of 8.3/patient (no lesion‐size limit) and 3.4/patient (10 mm3 lesion size limit).Data ConclusionA deep‐learning approach using multisequence MRI can automatically detect and segment brain metastases with high accuracy.Level of Evidence: 3Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:175–182.
Persistent easterly winds leading to precipitation in the Atlantic Coast of Patagonia
Authors: Agosta Eduardo A. , Martin Paula B. , Serio Leonardo A. 
Published: May 2019

AbstractThe relationship between daily precipitation and unusually persistent easterly wind recorded at station level along the coast of Eastern Patagonia is examined. Easterly wind events that persist for more than 20 h (E) are infrequent in Comodoro Rivadavia (CMR); but in about 80% of the times they do occur daily precipitation exceeds 1 mm. Although 2‐day persistent easterlies (2E) occur only about 1% of the time in CMR they are associated with 20% of the >75% percentile rain events. The occurrence of precipitation days (P ≥ 1 mm) during 2E events (P1&2E) is far from randomness for most stations. For daily P1&2E events in CMR, the convergence of westward moisture flux from the Atlantic is the key. Its daily frequency shifts towards Niño (44%), followed by Neutral 35 (32%), and Niña (25%) conditions. The probability of null precipitation days with westerlies was higher than 95% on average among the stations. The tropospheric circulation anomalous conditions associated with P1&2E events are characterized by a blocking‐like flow along 80–90°W, with anticyclonic anomalies near 60°–70°S and cyclonic anomalies in the mid‐latitudes. The strength of the anomalies is given by the meridional gradient of tropospheric circulation anomalies, stronger during the Niño phase. A P1&2E event at CMR is linked to active slow‐moving weather systems linked to tropospheric Rossby waves triggered by upper‐level tropospheric mass divergence anomalies in low latitudes. The source and trajectory these Rossby waves are different through ENSO phases. We have found that heavy precipitation over subtropical eastern Argentina during Niño precede CMR P1&2E events by 10 to 8 days. Daily P1&2E events contribute substantially to the mean precipitation total from April to June. The differential influence of the ENSO phases through the seasons of year is evident in such a contribution.
Synergistic effects triggered by simultaneous Toll‐like receptor‐2 and ‐3 activation in human periodontal ligament stem cells
Authors: Blufstein Alice , Behm Christian , Gahn Johannes , Uitz Oksana , Naumovska Ivana , Moritz Andreas , Rausch‐Fan Xiaohui , Andrukhov Oleh 
Published: May 2019

AbstractBackgroundAlthough periodontitis is associated with disruption of the host‐microbial homeostasis, viruses are currently discussed to influence disease progression. Viral pathogens are recognized by Toll‐like receptor (TLR)‐3, which engages a different signaling pathway than other TLRs. This study aimed to investigate the effect of TLR‐3 agonist polyinosinic:polycytidylic acid (Poly I:C) on the expression of inflammatory markers and bone metabolism proteins by human periodontal ligament stem cells (hPDLSCs) compared with TLR‐2 agonist Pam3CSK4, which mimics the effect of bacterial lipoproteins. To assess potential combined effects of bacterial and viral infections, hPDLSCs response to simultaneous TLR‐2 and TLR‐3 activation was investigated.MethodsHPDLSCs were stimulated with Poly I:C (0.0001‐1 µg/mL), Pam3CSK4 (1 µg/mL), and their combinations for 24 hours. Gene expression and protein levels of interleukin (IL)‐6, IL‐8, monocyte chemoattractant protein (MCP)‐1, and osteoprotegerin (OPG) were measured with qPCR and ELISA.ResultsProduction of IL‐6, IL‐8, MCP‐1, and OPG was significantly increased by Poly I:C or Pam3CSK4 to a similar extent. The levels of all inflammatory mediators induced by simultaneous stimulation with Poly I:C and Pam3CSK4 were significantly higher compared with single stimuli as well as to their summed response. Gene expression and protein levels of OPG were enhanced by Poly I:C, but by lesser extent than by Pam3CSK4. OPG levels upon simultaneous stimulation with Pam3CSK4 and Poly I:C were significantly lower compared with Pam3CSK4 stimulation alone.ConclusionsSimultaneous TLR‐2 and TLR‐3 activation synergistically triggers IL‐6, IL‐8, and MCP‐1 production, which was not observed for OPG. These findings suggest that TLR‐3 activation by viral infections might promote periodontitis progression.
Trend of surgery for orbital cellulitis: An analysis of state inpatient databases
Authors: Jiramongkolchai Pawina , Lander Daniel P. , Kallogjeri Dorina , Olsen Margaret A. , Keller Matthew , Schneider John S. , Lee Jake J. , Jiramongkolchai Kim , Piccirillo Jay F. 
Published: May 2019

Objectives/HypothesisTo evaluate the trend and factors associated with surgical management of orbital cellulitis.Study DesignRetrospective database study.MethodsStudy using the State Inpatient Databases (SIDs) from 2008 to 2015. Patients with an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD‐9‐CM) diagnosis code for orbital cellulitis were identified in the SIDs for the following states: Arkansas, Florida, Iowa, Maryland, Nebraska, New York, and Wisconsin. Surgery was defined as an ICD‐9‐CM procedure code for orbitotomy and/or functional endoscopic sinus surgery. The trend of surgery over time was evaluated using the Cochran‐Armitage test. Multivariable logistic regression models were used to identify patient‐ and hospital‐level factors associated with surgery.ResultsFrom 2008 to 2013, the number of hospitalizations for orbital cellulitis ranged from 1,349 to 1,574, but declined to 865 in 2014. From 2008 to 2015, the number of surgeries ranged from 103 to 154. For children (n = 3,041), age, ophthalmologic comorbidity, and conjunctival edema were significantly associated with surgery, whereas for adults (n = 7,961), male gender, private insurance, optic neuritis, and cranial nerves III/VI/VI palsy were associated with surgery.ConclusionsAlthough the number of inpatient hospitalizations for orbital cellulitis has markedly declined, the number of surgeries for orbital cellulitis has remained fairly stable, leading to an observed higher proportion of hospitalized patients undergoing surgery. Future directions include extending the time frame to the present day to assess current rates of hospitalization and surgery. Knowledge of surgical trends and patient‐ and hospital‐level characteristics associated with surgery may help improve management guidelines for and understanding of this vision‐threatening disease.Level of EvidenceNALaryngoscope, 130:567–574, 2020
Halophyte residue decomposition and microbial community structure in coastal soil
Authors: Chaudhary Doongar R. , Rathore Aditya P. , Jha Bhavanath 
Published: May 2019

AbstractSaltmarshes are known for higher primary productivity and play a crucial role in carbon‐sequestration, nutrient‐cycling, and ecological services; however, scarce information are available on halophyte residue mineralization and microbial community structure during decomposition. Soil microcosms with residues (1% w/w) of three dominant halophytes (Aeluropus lagopoides, Arthrocnemum indicum, and Suaeda nudiflora) and one control were incubated under laboratory conditions and sampled at 1, 5, 10, 20, 40, and 90 days to link the microbial community structure and residues decomposition in degraded coastal soil. Samples were subjected to identification of active microbial groups and residue mineralization using fatty acid methyl ester (FAME) and CO2 evolution methods, respectively. Biochemical composition of residues was also analyzed. Cumulative CO2 evolution was elevated in residue‐amended soils compared with control, and it was highest in Arthrocnemum followed by Suaeda, Aeluropus, and control soil. The Aeluropus residue decomposed slower than others due to its high C/N ratio and low protein content. The contents of total FAME and biomarker FAMEs of microbial groups (bacterial, fungal, and actinomycetes) responded positively to the residue amendments compared with control, which indicate the improvement in soil microbial biomass. Soils amended with Suaeda had the highest amount of total (76.8 nmol/g) and fungal FAMEs (6.7 nmol/g), and bacterial (28.6 nmol/g) and actinomycete (3.0 nmol/g) FAMEs were elevated in Arthrocnemum amended soil. At the same time, soils amended with Suaeda (6.2%), Arthrocnemum (28.4%), and control (15.4%) had the greatest abundance of fungal, Gram‐negative and Gram‐positive FAME biomarkers, respectively. The present study suggests that residue of halophyte species affected the abundance of fungal and bacterial biomarkers, and the microbial community structure.
An intuitionistic formula hierarchy based on high‐school identities
Authors: Brock‐Nannestad Taus , Ilik Danko 
Published: May 2019

AbstractWe revisit the notion of intuitionistic equivalence and formal proof representations by adopting the view of formulas as exponential polynomials. After observing that most of the invertible proof rules of intuitionistic (minimal) propositional sequent calculi are formula (i.e., sequent) isomorphisms corresponding to the high‐school identities, we show that one can obtain a more compact variant of a proof system, consisting of non‐invertible proof rules only, and where the invertible proof rules have been replaced by a formula normalization procedure. Moreover, for certain proof systems such as the G4ip sequent calculus of Vorob'ev, Hudelmaier, and Dyckhoff, it is even possible to see all of the non‐invertible proof rules as strict inequalities between exponential polynomials; a careful combinatorial treatment is given in order to establish this fact. Finally, we extend the exponential polynomial analogy to the first‐order quantifiers, showing that it gives rise to an intuitionistic hierarchy of formulas, resembling the classical arithmetical hierarchy, and the first one that classifies formulas while preserving isomorphism.
Physical Activity Improves Lipid and Weight‐Loss Outcomes After Metabolic Bariatric Surgery in Adolescents with Severe Obesity
Authors: Price Paula Holland , Kaizer Alexander M. , Daniels Stephen R. , Jenkins Todd M. , Inge Thomas H. , Eckel Robert H. 
Published: May 2019

ObjectiveThis study tested the hypothesis that physical activity improves cardiovascular disease–related lipids beyond that associated with weight loss in adolescents with severe obesity after metabolic/bariatric surgery (MBS).MethodsObjective activity monitor data from 108 participants of the Teen Longitudinal Assessment of Bariatric Surgery (Teen‐LABS) study from baseline to 3 years post MBS were used. Primary outcomes included absolute change in LDL cholesterol (LDL‐C) and non‐HDL cholesterol (non‐HDL‐C) from baseline. Baseline measurement, visit, surgical procedure, and percent change in iliac waist circumference or BMI from baseline in linear regression models were adjusted for use of generalized estimating equations. PROC TRAJ in SAS generated optimal activity trajectories based on individual step count.ResultsDespite low step counts and slow cadence, differences by activity trajectory were found. Greater absolute decreases in LDL‐C and non‐HDL‐C (−15 mg/dL [95% CI: −28 to −2], P  = 0.026; and −15 mg/dL [95% CI: −28 to −1], P  = 0.035), respectively, were associated with more activity. More activity was associated with greater resolution of triglycerides, LDL‐C, and non‐HDL‐C dyslipidemia and with greater weight loss 3 years post MBS.ConclusionsMore activity in adolescents was associated with improvements in cardiovascular disease–related lipid measures and weight loss after MBS.