bluuebunny/crossref_metadata_2025_split huggingface dataset:
NK cell and macrophages confer prognosis and reflect immune status in osteosarcoma
Authors: Yang Xianliang , Zhang Wenbin , Xu Panfeng 
Published: December 2018

AbstractOsteosarcoma (OS) is a common primary malignant bone tumor in young adolescents. About 30% of patients with OS have a recurrence, and the overall survival after OS recurrence is not good. In this study, we aimed to analyze and identify factors that influence prognosis after OS relapse. We retrieved the Gene Expression Omnibus data set and collected a series of transcriptome data with clinical information, including microRNA (miRNA) and messenger RNA (mRNA) expression profiles in recurrent OS. Upon comparison of the dysregulated genes of survival status in the recurrent OS samples, it was found that there were 268 differential expressed (DE) mRNAs and six DE miRNAs. These genes are related to pathways in cancer. We also predicted the interaction networks of these DE mRNAs and miRNAs. Further, we applied cibersort to estimate the proportion of immune cell types and we discovered that natural killer cells and macrophages have different abundance between good prognosis and poor prognosis. Our study indicates that for recurrent OS samples, there are several differences between these two groups, including gene expression and the status of immune activation. The immunity status is a candidate signature for disease prediction, prevention, and therapy choices.
Elevated expression of circular RNA circ_0008450 predicts dismal prognosis in hepatocellular carcinoma and regulates cell proliferation, apoptosis, and invasion via sponging miR‐548p
Authors: Zhang Juan , Chang Yuxia , Xu Lijun , Qin Lijie 
Published: December 2018

AbstractHepatocellular carcinoma (HCC) is one of the most frequent malignancies and a main cause of global cancer mortality. In the past decade, circular RNAs (circRNAs) have been proved to play key roles in various cancers. Previously, circ_0008450 was identified upregulated in HCC tissues by high‐throughput circRNA sequencing. In this study, quantitative real‐time polymerase chain reaction was used to evaluate the expression level of circ_0008450 in human HCC tumor and corresponding nontumor tissue samples, and the association between circ_0008450 expression and clinicopathologic features of patients with HCC was also analyzed. After that, the functions of circ_0008450 in biological behaviors of HCC cells were determined by cell counting kit‐8, colony formation, flow cytometry, and the transwell assays. The mechanism of circ_0008450 was explored by the bioinformatic analysis and dual‐luciferase reporter assay. The expression of circ_0008450 is upregulated in HCC tissue specimens and cell lines. Patients with a high circ_0008450 expression usually bear a lower 5‐year survival rate. Silencing of circ_0008450 in Huh‐7 cells inhibited cell viability, migration, and invasion, whereas cell apoptosis was increased. Conversely, its overexpression in HepG2 cells leads to absolutely inverse results. In addition, circ_0008450 was proved to be a sponge of miR‐548p. The oncogenic role of circ_0008450 was partially attributed to its suppression on miR‐548p. This study implies a new target for the treatment of HCC.
The influence of receptor activity–modifying protein‐1 overexpression on angiogenesis in mouse brain capillary endothelial cells
Authors: Zhang Qin , Guo Yanjun , Chen Huilu , Jiang Yixuan , Tang Haiyang , Gong Ping , Xiang Lin 
Published: December 2018

AbstractReceptor activity–modifying protein‐1 (RAMP1) is highly expressed in the heart and vasculature, indicating that it might be related to the vascular system. However, the effects of RAMP1 on angiogenesis and the intrinsic mechanisms underlying this process remain unclear. Here, we verified that RAMP1 is a critical regulator of angiogenesis in a mouse brain capillary endothelial cell line (bEnd.3). We first constructed a RAMP1 overexpression lentiviral vector system and stably transfected bEnd.3 cells. We further showed that RAMP1 overexpression could lead to bEnd.3 migration and capillary tube formation in Matrigel without exogenous calcitonin gene–related peptide (CGRP) treatment. At the same time, RAMP1 overexpression had little effect on proliferation. More importantly, vascular endothelial growth factor (VEGF) and CGRP expression levels were not significantly higher in RAMP1‐overexpressing cells than in control cells (P > 0.05), indicating that RAMP1 did not function through upregulating VEGF or CGRP expression in bEnd.3 cells. Strikingly, RAMP1 transfection increased adrenomedullin 2 (AM2) expression levels (
P < 0.05). Taken together, these data contribute to a better understanding of the molecular mechanisms of RAMP1 in angiogenesis.
Evaluation of vitamin D3 deficiency: A population‐based study in northeastern Iran
Authors: Esmaeili Seyed‐Alireza , Mohammadian Saeed , Radbakhsh Shabnam , Momtazi‐Borojeni Amir Abbas , Kheirmand Parizi Payam , Atabati Hadi , Mardani Fatemeh , Saburi Ehsan , Moghaddam Abbas Shapouri 
Published: December 2018

AbstractBackground and AimIn recent years, vitamin D deficiency has become a major worldwide problem that can exert harmful effects. The aim of the present study was to evaluate the sex‐ and age‐related prevalence of vitamin D deficiency in people from Mashhad, northeastern Iran.MethodsIn this cross‐sectional study conducted over a period of 1 year (2015‐2016), 7504 subjects who referred to Mashhad medical centers were randomly enrolled in the study. The study population was divided into four groups based on sex and age, as following: group 1, 6 to 18 years; group 2, 19 to 35 years; group 3, 36 to 50 years; and group 4, 51 to 65 years. Since vitamin D levels <10, 10 to 20, and 20 to 30 ng/mL are considered as severe, moderate, and mild deficiency, respectively, we used these criteria for categorizing our population.ResultsOf the total population in our study, 65.26% (4902; 57.81% of men and 72.07% of women) showed some degree of vitamin D deficiency. In addition, we found that vitamin D deficiency was common in all age groups (6‐18, 19‐35, 36‐50, and 51‐65 years), and more common in women (58.5%, 80.12%, 63.83%, and 88.44%, respectively) than men (41.66%, 59.86%, 44.97%, and 84.75%, respectively).ConclusionVitamin D deficiency is a major health problem in all age groups and is more common in women. This information would help to provide a progressive prevention program to maintain health and manage some of the vitamin‐related disorders and diseases that especially affect women.
Role of the transforming growth factor‐β signaling pathway in the pathogenesis of colorectal cancer
Authors: Soleimani Atena , Pashirzad Mehran , Avan Amir , Ferns Gordon A. , Khazaei Majid , Hassanian Seyed Mahdi 
Published: December 2018

AbstractThe transforming growth factor‐β (TGF‐β) signaling pathway plays an important role in cancer cell proliferation, growth, metastasis, and apoptosis. It has been shown that TGF‐β acts as a tumor suppressor in the early stages of the disease, and as a tumor promoter in its late stages. Mutations in the TGF‐β signaling components, the TGF‐β receptors and cytoplasmic signaling transducers, are frequently observed in colorectal carcinomas. Exploiting specific TGF‐β receptor agonist and antagonist with antitumor properties may be a way of controlling cancer progression. This review summarizes the regulatory role of TGF‐β signaling in the pathogenesis of colorectal cancer.
Outcomes among pregnant recently incarcerated women attending a reentry transitions clinic
Authors: Morse Diane S. , Wilson John L. , Driffill Nicole J. , Lauture Joloire , Khan Ali , King‐Turner Stella O. 
Published: December 2018

AbstractThis mixed methods retrospective case series and qualitative descriptive study describes pregnancy outcomes during the postincarceration period. A retrospective case series via electronic medical record chart review from a subset of women attending a postincarceration primary care clinic with a condition of interest (pregnancy) described demographics, substance use, diagnoses, and pregnancy outcomes. We compared 27 pregnant to 79 nonpregnant women and contextualized quantitative data with qualitative descriptive vignettes. Twenty‐seven women completed 29 pregnancies (2 women with 2 deliveries each), all of which were unplanned; there were 11 live births, 8 pregnant at study closure, 7 miscarriages, and 3 terminations. Although substance use history was high, rates were higher among nonpregnant women (92% vs 74%). Among the 5 births, 4 tested positive for substance use during pregnancy. All 11 infants had pregnancy or delivery complications. Although 7 of the 10 pregnant women with live births had prior pregnancy complications, only 4 were placed in a special care obstetrics clinic. Although unplanned pregnancies were common, most births did not demonstrate maternal substance use. All live births had pregnancy or delivery complications, but few were accepted to specialist prenatal care, suggesting potential considerations for recently incarcerated women.
Systemic Tofacitinib Concentrations in Adult Patients With Atopic Dermatitis Treated With 2% Tofacitinib Ointment and Application to Pediatric Study Planning
Authors: Purohit Vivek S. , Ports William C. , Wang Cunshan , Riley Steve 
Published: December 2018

AbstractAtopic dermatitis is a chronic eczematous, pruritic, inflammatory skin condition affecting children and adults. Tofacitinib is a Janus kinase inhibitor. The efficacy, safety, and pharmacokinetics of 2% tofacitinib ointment twice daily have been evaluated in a 4‐week phase 2a multisite randomized, double‐blind, vehicle‐controlled, parallel‐group study (NCT02001181) in adult patients with mild to moderate atopic dermatitis and 2% to 20% body surface area (BSA) involvement. Tofacitinib ointment demonstrated significantly greater efficacy versus vehicle for all efficacy end points and had an acceptable safety profile. Predose and postdose pharmacokinetic samples were collected in week 2 and week 4. The objective of this analysis was to assess if predicted mean tofacitinib concentrations with topical application at higher treated BSA across age groups would exceed relevant concentration thresholds based on oral doses of tofacitinib. In this analysis, the pharmacokinetic concentrations were characterized using a linear mixed‐effects model. The model was used to predict concentrations for adults with higher (>20%) treatable BSA. Adult concentrations were used to extrapolate concentrations to a pediatric population (2 to 17 years) using allometric principles. The predicted systemic concentrations for 2% tofacitinib ointment in both adult and pediatric populations at treated BSA ≤50% for a mild to moderate atopic dermatitis population did not exceed those reported for the 10th percentile of observed oral tofacitinib 5‐mg twice‐daily doses in patients with moderate to severe plaque psoriasis. The methodology described will enable analysis and prediction of systemic concentrations for topical agents.
An LDHa single allele CHO cell mutant exhibits altered metabolic state and enhanced culture performance
Authors: Wilkens Camila A , Vishwanathan Nandita , Baltes Nicholas J , Lucero Alicia T , Hu Wei‐Shou , Gerdtzen Ziomara P 
Published: December 2018

AbstractBACKGROUNDReducing lactate production in animal cell cultures has been reported to improve cell culture performance and productivity of recombinant protein. A novel genome editing tool, CRISPR/Cas, has been used widely to induce double‐strand breaks in the genome and introduce targeted mutations efficiently.RESULTSIn the present work, we used a publicly available human‐codon optimized CRISPR/Cas system to introduce mutations in one of the LDHa gene copies to obtain an LDHa single‐allele knockout Chinese hamster ovary (CHO) cell clone to analyze its effect over cell metabolism. Fed‐batch cultures were conducted in order to evaluate the culture performance of mutant cells. Results show that cell growth was reduced and metabolism was modified by the LDHa single‐allele knockout, whereas specific protein rate and volumetric production were greatly enhanced. Additionally, the first in‐depth analysis of the metabolic effects of LDHa single allele knockout is presented.CONCLUSIONBy using CRISPR/Cas we were able to knock down LDHa, showing improved culture productivity. Metabolic flux analysis revealed higher fluxes in the TCA cycle in the mutant cell than in the parental cell, indicating that LDHa mutant cells have an enhanced energy metabolism, which can be attributed mainly to a higher catabolism of amino acids. © 2018 Society of Chemical Industry
Supercritical fluid extraction for enhancing polyphenolic compounds production from olive waste extracts
Authors: Caballero Ashley S , Romero‐García Juan M , Castro Eulogio , Cardona Carlos A 
Published: December 2018

AbstractBACKGROUNDA number of residues are produced during the olive oil extraction process, such as crushed pits, olive leaves, pomace and exhaust olive pomace. In addition, pruning of olive trees results in a huge amount of biomass. All of these lignocellulosic materials constitute a source of energy and chemicals that can be used as raw materials in biorefineries. Among them, antioxidants are of particular interest due to their potential applications in pharmaceutical and food industry.RESULTSSupercritical fluid extraction (SFE) was applied on three different olive residues – pruning biomass, leaves and exhaust pomace. In this, 60% ethanol was used as cosolvent at three different pressure levels, 200, 250 and 300 bar. The best conditions for each residue were determined and compared with conventional extraction. Results show that 300 bar was the best pressure for SFE in terms of antioxidant activity of the extracts. The main polyphenolic compounds also were identified, among which hydroxytyrosol, chlorogenic acid, caffeic acid and ferulic acid were present.CONCLUSIONSFE at 300 bar proved to be the best option for obtaining a high‐activity antioxidant extract from olive leaves, exhaust pomace and pruning biomass, with hydroxytyrosol the prominent compound detected. This procedure could be integrated in a biorefinery based on olive‐derived biomass. © 2018 Society of Chemical Industry
Embryogenesis and early larval development in wild‐caught Levantine scraper,Capoeta damascina(Valenciennes, 1842)
Authors: Zadmajid Vahid , Sørensen Sune Riis , Butts Ian Anthony Ernest 
Published: December 2018

AbstractLevantine scraper,Capoeta damascinais a candidate species for future stock assessments, conservation studies, and hatchery efforts. Herein, we documented embryonic and early larval development, from egg activation to the exogenous feeding period, using morphological and histological landmarks. Embryos were obtained by in vitro fertilization from hormonally induced wild‐caught broodstock, and subsequent development was monitored at temperatures coinciding with native conditions. Embryonic development from fertilization to hatch lasted ~105–110 hr. Larvae emerged with unpigmented eyes and body morphology, as well as an undifferentiated digestive tract. The mouth was closed at hatch by the oropharyngeal membrane and opened by the early endogenous feeding period. Trabeculae cartilage, quadrate bone, and Meckel's cartilage of the endoskeleton were present during the endogenous feeding period. During this period, the larvae underwent considerable changes in craniofacial morphology, locomotion, and organogenesis of the digestive tract. The cartilaginous floor of the neurocranium developed and the first four ceratobranchials appeared simultaneously at the end of endogenous feeding period. The digestive tract was differentiated into buccopharynx, esophagus, and small intestine during the endogenous feeding period. The intestinal valve and numerous longitudinal folds at the posterior region of the intestine formed together by the endo–exogenous feeding period. Major developmental events in retinogenesis occurred during the endogenous feeding period. When larvae entered exogenous feeding the mouth was fully‐functional. Additionally, liver size and eye diameter increased. Our analysis of embryonic and early larval development in Levantine scraper aligned with other freshwater fishes.
Increased perfusion in dynamic gadolinium‐enhanced MRI correlates with areas of bone repair and of bone necrosis in patients with Kienböck's disease
Authors: Müller Gunilla , Månsson Sven , Müller Markus F. , Johansson Martin , Björkman Anders 
Published: December 2018

BackgroundOsteonecrosis of the lunate, Kienböck's disease, can lead to fragmentation of the lunate, carpal collapse, and severe osteoarthritis. Since the etiology of Kienböck's disease is impaired circulation, a diagnostic method capable of assessing perfusion would be valuable. Recent studies have suggested that dynamic contrast‐enhanced (DCE) MR examinations at 3 T can assess perfusion in healthy carpal bones.PurposeTo evaluate the use of DCE‐MR for assessing perfusion in the lunate bone in patients with Kienböck's disease. Furthermore, to compare perfusion with histopathology with a focus on bone viability.Study TypeProspective case–control study.PopulationFourteen patients with Kienböck's disease and a control group of 19 healthy subjects.Field Strength: 3 T with T1‐weighted fat‐saturated contrast‐enhanced gradient echo series.AssessmentFeatures of the enhancement curves from the DCE‐MR examinations, time to peak (TTP), maximum slope (MS), and maximum enhancement (ME) assessed by a radiologist. Six of 14 patients were surgerized with lunate excision, allowing comparison between features of the enhancement curves and histopathology.Statistical TestsMann–Whitney U‐test. P < 0.05 was considered a statistically significant difference.ResultsPatients with Kienböck's disease showed significantly higher and faster perfusion parameters compared with the control group, the mean value of the TTP in patients was 126.73 sec, in controls 189.79 sec (P = 0.024), ME in patients 173.55 AU, in controls 28.46 AU (P < 0.001), and MS in patients 5.04 AU, in controls 1.06 AU (P < 0.001). When compared with histopathology, increased perfusion was seen in areas of bone formation but also in necrosis. Areas of normal bone showed low perfusion.Data ConclusionDCE‐MRI at 3 T can diagnose altered perfusion in patients with Kienböck's disease. Increased perfusion cannot definitely be used as a marker of bone viability.Level of Evidence: 1Technical Efficacy: Stage 3J. Magn. Reson. Imaging 2019;50:481–489.
TNF‐α enhances apoptosis by promoting chop expression in nucleus pulposus cells: role of the MAPK and NF‐κB pathways
Authors: Zhang Jian , Wang Xiaolin , Liu Hui , Li Zemin , Chen Fan , Wang Hua , Zheng Zhaomin , Wang Jianru 
Published: December 2018

ABSTRACTCHOP has been shown to be involved in AF cells apoptosis and disc degeneration in a rat model. The aim of this study was to investigate the regulatory effects of TNF‐α on C/EBP homologous protein (CHOP) and the role of CHOP in nucleus pulposus (NP) cell apoptosis. The effects of TNF‐α on chop were measured by qPCR, Western blot, and immunofluorescence. TNF receptor involvement was analyzed by small interfering RNA (siRNA), Western blotting, immunofluorescence, and qPCR. The effects of NF‐κB and MAPK on TNF‐α‐mediated chop promoter activity were studied using siRNAs, Western blotting, immunofluorescence, and qPCR. The regulatory effects of TNF‐α‐induced CHOP on Bcl‐2 and Bax were studied using siRNAs, Western blotting, immunofluorescence, and qPCR. Flow cytometric and TUNEL analyses were performed to investigate the effects of chop on NP cell apoptosis. Increased CHOP expression was observed in NP cells after TNF‐α treatment. Treatment of cells with TNF receptor, NF‐κB, and ERK/JNK‐MAPK inhibitors or siRNAs abolished the effects of cytokines on CHOP expression. Pharmacological siRNA knockdown of chop promoted Bax, decreased Bcl‐2, and attenuated TNF‐α‐mediated cell apoptosis. During intervertebral disc degeneration (IVDD), TNF‐α binds to TNF receptors and controls the JNK/ERK‐MAPK, and NF‐κB signaling pathways in NP cells, increasing CHOP expression. This change up‐regulates the pro‐apoptotic protein Bax and down‐regulates the anti‐apoptosis protein Bcl‐2, inducing cell apoptosis. This study suggests a potential therapeutic target for controlling the inflammatory‐induced apoptosis associated with IVDD. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
Determination of acidic drugs in biological and environmental matrices by membrane‐based dual emulsification liquid‐phase microextraction followed by high‐performance liquid chromatography
Authors: Moradi Peyman , Asghari Alireza 
Published: December 2018

AbstractA simple method is introduced providing a highly clean microextraction for the determination of some anti‐inflammatory drugs as the model analytes in human urine and environmental matrices. This method is based upon the implementation of two consecutive emulsification liquid‐phase microextractions, which are separated by a syringe filtration step. In this method, the organic extraction solvent (dihexyl ether) is dispersed into the aqueous sample solution (20 mL), and the resulting cloudy mixture is passed through a hydrophilic polytetrafluoroethylene syringe filter. By this action, the extraction phase containing the analytes and many interfering species that could be transferred into the organic phase is retained behind the hydrophilic membrane. The filter is then detached from the syringe and attached to another syringe containing an aqueous solution (pH 12.0, 150 μL), and by the in‐syringe dispersion of the organic phase into the aqueous phase, the analytes are selectively back‐extracted into the aqueous phase. The developed method is centrifuge‐free and very simple, and provides a high sample clean‐up in a few minutes. Under the optimized experimental conditions, the developed method provided a linearity in the range of 2.0–2000 ng/mL, a low limit of detection (0.5 ng/mL), and enrichment factors of 47–53.
The Effects of Dual‐Task Cognitive Interference and Environmental Challenges on Balance in Huntington's Disease
Authors: Purcell Nicollette L. , Goldman Jennifer G. , Ouyang Bichun , Bernard Bryan , O'Keefe Joan A. 
Published: December 2018

ABSTRACTBackgroundHuntington's disease (HD) is characterized by chorea, balance and gait impairments, and cognitive deficits, which increase fall risk. Dual task (DT) and environmentally challenging paradigms reflect balance related to everyday life. Furthermore, the impact of cognitive deficits on balance dysfunction and falls in HD is unknown.ObjectiveTo determine the impact of DT interference, sensory feedback, and cognitive performance on balance and falls in HD.MethodsSeventeen participants with HD (55 ± 9.7 years) and 17 age‐matched controls (56.5 ± 9.3 years) underwent quantitative balance testing with APDM inertial sensors. Postural sway was assessed during conditions of manipulated stance, vision, proprioception, and cognitive demand. The DT was a concurrent verbal fluency task. Neuropsychological assessments testing multiple cognitive domains were also administered.ResultsHD participants exhibited significantly greater total sway area, jerk, and variability under single‐task (ST) and DT conditions compared to controls (P = 0.0002 – < 0.0001). They also demonstrated greater DT interference with vision removed for total sway area (P = 0.01) and variability (P = 0.02). Significantly worse postural control was observed in HD with vision removed and reduced proprioception (P = 0.001 – 0.01). Decreased visuospatial performance correlated with greater total sway and jerk (P = 0.01; 0.009). No balance parameters correlated with retrospective falls in HD.ConclusionsHD participants have worse postural control under DT, limited proprioception/vision, and greater DT interference with a narrowed base and no visual input. These findings may have implications for designing motor and cognitive strategies to improve balance in HD.