bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of aberrant circulating miRNAs in Parkinson's disease plasma samples
Authors: Chen Lei , Yang Junxiu , Lü Jinhui , Cao Shanshan , Zhao Qian , Yu Zuoren 
Published: February 2018

AbstractObjectiveTo detect the aberrant expression of circulating miRNAs and explore the potential early diagnostic biomarkers in patients with Parkinson's disease (PD).MethodsPlasma samples were collected from 25 treatment‐naïve PD‐diagnosed patients and 25 healthy controls followed by a real‐time PCR‐based miRNA screening analysis of neuron disease‐related miRNAs.ResultsA subset of miRNAs with aberrant expression levels in the plasma of PD‐diagnosed patients were identified including upregulation of miR‐27a and downregulation of let‐7a, let‐7f, miR‐142‐3p, and miR‐222 with the AUC values more than 0.8 derived from the receiver operating characteristic curves.ConclusionsThe high sensitivity and specificity of the circulating miRNAs may enable early diagnosis of PD. The study provides a group of novel miRNA candidates for detecting PD.
Prognostic variables for temporal lobe injury after intensity modulated‐radiotherapy of nasopharyngeal carcinoma
Authors: Feng Mei , Huang Yecai , Fan Xigang , Xu Peng , Lang Jinyi , Wang Dian 
Published: February 2018

AbstractTo determine predictive factors for temporal lobe injury (TLI) in nasopharyngeal carcinoma patient (NPC) treated with intensity‐modulated radiation therapy (IMRT). A total of 695 NPC cases treated with IMRT were retrospectively analyzed. TLI was diagnosed on MRI images. Volume‐dose histograms for 870 evaluable temporal lobes were analyzed, and the predictive factors for the occurrence of TLI was evaluated. Receiver operating characteristic curve (ROC) and Logistic regression analysis was used to determine volume‐dose parameters that predict temporal lobe injury (TLI). Univariate and multivariate analysis were used to analyze the predictive factors for TLI. The radiation dose‐tolerance model of temporal lobe was calculated by logistic dose‐response model. The median follow‐up time was 73 months. A total of 8.5% patients were diagnosed with TLI. Among all the volume‐dose parameters, logistic regression model showed D2cc (the dose Gray delivered to 2 cubic centimeter volume) was an only independent predictive factor. Multivariate analysis showed D2cc of temporal lobe, fraction size of prescription, T stage, and chemotherapy were the independent predictive factors for TLI. Logistic dose‐response model has indicated the TD5/5 and TD50/5 of D2cc are 60.3 Gy and 76.9 Gy, respectively. D2cc of temporal lobe, fraction size of prescription, T stage, and chemotherapy were the possible independent predictive factors for TLI after IMRT of NPC. Biologic effective doses (TD5/5 and TD50/5) of D2cc are considered to prevent TLI.
Establishment and characterization of in vivo orthotopic bioluminescent xenograft models from human osteosarcoma cell lines in Swiss nude and NSG mice
Authors: Marques da Costa Maria Eugenia , Daudigeos‐Dubus Estelle , Gomez‐Brouchet Anne , Bawa Olivia , Rouffiac Valerie , Serra Massimo , Scotlandi Katia , Santos Conceição , Geoerger Birgit , Gaspar Nathalie 
Published: February 2018

AbstractOsteosarcoma is one of the most common primary bone tumors in childhood and adolescence. Metastases occurrence at diagnosis or during disease evolution is the main therapeutic challenge. New drug evaluation to improve patient survival requires the development of various preclinical models mimicking at best the complexity of the disease and its metastatic potential. We describe here the development and characteristics of two orthotopic bioluminescent (Luc/mKate2) cell‐derived xenograft (CDX) models, Saos‐2‐B‐Luc/mKate2‐CDX and HOS‐Luc/mKate2‐CDX, in different immune (nude and NSG mouse strains) and bone (intratibial and paratibial with periosteum activation) contexts. IVIS SpectrumCT system allowed both longitudinal computed tomography (CT) and bioluminescence real‐time follow‐up of primary tumor growth and metastatic spread, which was confirmed by histology. The murine immune context influenced tumor engraftment, primary tumor growth, and metastatic spread to lungs, bone, and spleen (an unusual localization in humans). Engraftment in NSG mice was found superior to that found in nude mice and intratibial bone environment more favorable to engraftment compared to paratibial injection. The genetic background of the two CDX models also led to distinct primary tumor behavior observed on CT scan. Saos‐2‐B‐Luc/mKate2‐CDX showed osteocondensed, HOS‐Luc/mKate2‐CDX osteolytic morphology. Bioluminescence defined a faster growth of the primary tumor and metastases in Saos‐2‐B‐Luc/mKate2‐CDX than in HOS‐Luc/mKate2‐CDX. The early detection of primary tumor growth and metastatic spread by bioluminescence allows an improved exploration of osteosarcoma disease at tumor progression, and metastatic spread, as well as the evaluations of anticancer treatments. Our orthotopic models with metastatic spread bring complementary information to other types of existing osteosarcoma models.
Retracted: LncRNA HOTAIR influences cell growth, migration, invasion, and apoptosis via the miR‐20a‐5p/HMGA2 axis in breast cancer
Authors: Zhao Wenyan , Geng Donghua , Li Shuqiang , Chen Zhaofu , Sun Ming 
Published: February 2018

AbstractTo study the regulatory effect of lncRNA HOTAIR/miR‐20a‐5p/HMGA2 axis on breast cancer (BC) cell growth, cell mobility, invasiveness, and apoptosis. The microarray data of lncRNAs and mRNAs with differential expression in BC tissues were analyzed in the Cancer Genome Atlas (TCGA) database. LncRNA HOX transcript antisense RNA (lncRNA HOTAIR) expression in BC was assessed by qRT‐PCR. Cell viability was confirmed using MTT and colony formation assay. Cell apoptosis was analyzed by TdT‐mediated dUTP nick‐end labeling (TUNEL) assay. Cell mobility and invasiveness were testified by transwell assay. RNA pull‐down and dual luciferase assay were used for analysis of the correlation between lncRNA HOTAIR and miR‐20a‐5p, as well as relationship of miR‐20a‐5p with high mobility group AT‐hook 2 (HMGA2). Tumor xenograft study was applied to confirm the correlation of lncRNA HOTAIR/miR‐20a‐5p/HMGA2 axis on BC development in vivo. The expression levels of the lncRNA HOTAIR were upregulated in BC tissues and cells. Knockdown lncRNA HOTAIR inhibited cell propagation and metastasis and facilitated cell apoptosis. MiR‐20a‐5p was a target of lncRNA HOTAIR and had a negative correlation with lncRNA HOTAIR. MiR‐20a‐5p overexpression in BC suppressed cell growth, mobility, and invasiveness and facilitated apoptosis. HMGA2 was a target of miR‐20a‐5p, which significantly induced carcinogenesis of BC. BC cells progression was mediated by lncRNA HOTAIR via affecting miR‐20a‐5p/HMGA2 in vivo. LncRNA HOTAIR affected cell growth, metastasis, and apoptosis via the miR‐20a‐5p/HMGA2 axis in breast cancer.
Epiconus syndrome induced only in the erect standing position in a patient with L1 compression fracture: a representative case report
Authors: Kubota Kenji , Abe Koki , Orita Sumihisa , Inage Kazuhide , Suzuki Miyako , Sato Jun , Fujimoto Kazuki , Shiga Yasuhiro , Kanamoto Hirohito , Inoue Masahiro , Kinoshita Hideyuki , Norimoto Masaki , Umimura Tomotaka , Takahashi Kazuhisa , Ohtori Seiji 
Published: February 2018

Key Clinical MessageIn daily practice, when CT or MRI does not show a pathological lesion in a patient with persistent abnormal neurological signs, it is important to obtain imaging studies of the spine in dynamic position.
Safety profile of avelumab in patients with advanced solid tumors: A pooled analysis of data from the phase 1 JAVELIN solid tumor and phase 2 JAVELIN Merkel 200 clinical trials
Authors: Kelly Karen , Infante Jeffrey R. , Taylor Matthew H. , Patel Manish R. , Wong Deborah J. , Iannotti Nicholas , Mehnert Janice M. , Loos Anja H. , Koch Helga , Speit Isabell , Gulley James L. 
Published: February 2018

BACKGROUNDAntibodies targeting the programmed death‐ligand 1 (PD‐L1)/programmed cell death protein 1 (PD‐1) checkpoint may cause adverse events (AEs) that are linked to the mechanism of action of this therapeutic class and unique from those observed with conventional chemotherapy.METHODSPatients with advanced solid tumors who were enrolled in the phase 1 JAVELIN Solid Tumor (1650 patients) and phase 2 JAVELIN Merkel 200 (88 patients) trials received avelumab, a human anti–PD‐L1 IgG1 antibody at a dose of 10 mg/kg every 2 weeks. Treatment‐related AEs (TRAEs) were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0). In post hoc analyses, immune‐related AEs (irAEs) were identified via an expanded AE list and medical review, and infusion‐related reactions (IRRs) occurring ≤2 days after infusion and symptoms occurring ≤1 day after infusion and resolving ≤2 days after onset were identified based on prespecified Medical Dictionary for Regulatory Activities (MedDRA) terms.RESULTSOf the 1738 patients analyzed, grade ≥3 TRAEs occurred in 177 (10.2%); the most common were fatigue (17 patients; 1.0%) and IRR (10 patients; 0.6%). TRAEs led to discontinuation in 107 patients (6.2%) and death in 4 patients (0.2%). Grade ≥3 irAEs occurred in 39 patients (2.2%) and led to discontinuation in 34 patients (2.0%). IRRs or related symptoms occurred in 439 patients (25.3%; grade 3 in 0.5% [9 patients] and grade 4 in 0.2% [3 patients]). An IRR occurred at the time of first infusion in 79.5% of 439 patients who had an IRR, within the first 4 doses in 98.6% of 439 patients who had an IRR, and led to discontinuation in 35 patients (2.0%).CONCLUSIONSAvelumab generally was found to be well tolerated and to have a manageable safety profile. A minority of patients experienced grade ≥3 TRAEs or irAEs, and discontinuation was uncommon. IRRs occurred mainly at the time of first infusion, and repeated events were infrequent. Cancer 2018;124:2010‐7. © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Efferent projections of excitatory and inhibitory preBötzinger Complex neurons
Authors: Yang Cindy F. , Feldman Jack L. 
Published: February 2018

AbstractThe preBötzinger Complex (preBötC), a compact medullary region essential for generating normal breathing rhythm and pattern, is the kernel of the breathing central pattern generator (CPG). Excitatory preBötC neurons in rats project to major breathing‐related brainstem regions. Here, we provide a brainstem connectivity map in mice for both excitatory and inhibitory preBötC neurons. Using a genetic strategy to label preBötC neurons, we confirmed extensive projections of preBötC excitatory neurons within the brainstem breathing CPG including the contralateral preBötC, Bötzinger Complex (BötC), ventral respiratory group, nucleus of the solitary tract, parahypoglossal nucleus, parafacial region (RTN/pFRG or alternatively, pFL/pFV), parabrachial and Kölliker‐Füse nuclei, as well as major projections to the midbrain periaqueductal gray. Interestingly, preBötC inhibitory projections paralleled the excitatory projections. Moreover, we examined overlapping projections in the pons in detail and found that they targeted the same neurons. We further explored the direct anatomical link between the preBötC and suprapontine brain regions that may govern emotion and other complex behaviors that can affect or be affected by breathing. Forebrain efferent projections were sparse and restricted to specific nuclei within the thalamus and hypothalamus, with processes rarely observed in cortex, basal ganglia, or other limbic regions, e.g., amygdala or hippocampus. We conclude that the preBötC sends direct, presumably inspiratory‐modulated, excitatory and inhibitory projections in parallel to distinct targets throughout the brain that generate and modulate breathing pattern and/or coordinate breathing with other behaviors, physiology, cognition, or emotional state.
Overview of the Baculovirus Expression System
Authors: Chambers Adam C. , Aksular Mine , Graves Leo P. , Irons Sarah L. , Possee Robert D. , King Linda A. 
Published: February 2018

AbstractThis unit provides information on the replication cycle of insect baculovirus to provide an understanding of how this virus has been adapted for use as an expression vector for recombinant proteins in insect cells. We provide an overview of the virus structure and its unique bi‐phasic replication cycle, which has been exploited in developing the virus as an expression vector. We also review the development of the baculovirus expression vector system (BEVS), from the mid‐1980s to the present day in which the BEVS is now an established tool for the production of a range of recombinant proteins and multi‐protein complexes including virus‐like particles. We describe advances made to the BEVS to allow the rapid and easy production of recombinant viruses and developments to improve protein yield. We finish by describing the application of recombinant BacMam as vectors for the delivery of genes into mammalian and human cells. © 2018 by John Wiley & Sons, Inc.
Protein Detection in Gels Using Fixation
Authors: Beer Lynn A. , Speicher David W. 
Published: February 2018

AbstractThe most commonly used types of gels for separating proteins are SDS gels, either in a 1‐D format or as the second dimension of various 2‐D separations, and the most common methods of visualizing proteins in these gels use protein binding dyes after fixing the proteins in the gel matrix. In recent years, there has been a continuing trend away from preparing staining solutions in the laboratory to using commercially available kits, which are convenient, save time, have defined shelf lives, and may provide greater reproducibility than stains formulated in research laboratories. In general, when using commercial kits, satisfactory results can be readily obtained by following the manufacturer's protocols. This unit reviews commonly used fixation‐based stains and provides a number of manual formulations with staining protocols for those who prefer such staining methods. © 2018 by John Wiley & Sons, Inc.
Identification and functional analysis of a novel G310D variant in the insulin‐like growth factor 1 receptor (IGF1R) gene associated with type 2 diabetes in American Indians
Authors: Muller Yunhua L. , Skelton Graham , Piaggi Paolo , Chen Peng , Nair Anup , Kobes Sayuko , Hsueh Wen‐Chi , Knowler William C. , Hanson Robert L. , Baier Leslie J. , Bogardus Clifton 
Published: February 2018

AbstractAimsInsulin‐like growth factor 1 receptor (IGF1R) is involved in cell growth and glucose homeostasis. In the current study, the IGF1R locus was analysed as a candidate gene for type 2 diabetes (T2D) in American Indians.Materials and methodsWhole genome sequence data from 335 American Indians identified 3 novel missense variants in IGF1R. The associations of IGF1R variants with T2D, age of T2D onset and birth weight were analysed in a population‐based sample of 7701 American Indians.ResultsA novel glycine‐to‐aspartic acid substitution (G310D) in IGF1R was identified, which associated with T2D in a sex‐specific manner (Psex interaction = 0.02). In women, the aspartic acid (D) allele (frequency = 0.034) was associated with increased risk for T2D (n = 4292, P = 2.0 × 10−5 adjusted for age, birth year, and the first 5 genetic principal components; odds ratio [OR] = 2.23 [1.54‐3.23] per risk allele) and an earlier age of T2D onset (n = 4292, P = 2 × 10−4, hazard rate ratio = 1.45 [1.20‐1.75], Psex interaction = 0.05). Female carriers of the D‐allele also had lower birth weight (n = 1313, β = −163 g, P = .006, Psex interaction = 0.008). Among 85 siblings discordant for G310D, carriers of the D‐allele had shorter stature as compared with carriers of the G‐allele (β = −1.6 cm, P = .001, within family model). The G310D variant was functionally studied in vitro, where the D‐allele had a 22% increase (P = .0005) in FOXO1‐induced transcriptional activity, due to decreased activation of the PI3K/AKT pathway mediated through reduced IGF1R activity.ConclusionA unique G310D variant in IGF1R, which occurs in 6% American Indians, may impair IGF1R signalling pathways, thereby increasing the risk of T2D.
Adult spinal opioid receptor μ1 expression after incision is altered by early life repetitive tactile and noxious procedures in rats
Authors: van den Hoogen Nynke J. , van Reij Roel RI , Patijn Jacob , Tibboel Dick , Joosten Elbert A. J. 
Published: February 2018

ABSTRACTClinical and experimental data suggests that noxious stimulation at critical stages of development results in long‐term changes on nociceptive processing in later life. Here, we use an established, well‐documented rat model of repetitive noxious procedures closely mimicking the clinical situation in the NICU. In order to understand molecular changes underlying the long‐term consequences of repetitive stimulation of the developing nociceptive system the present study aims to analyze the presence of the µ‐opioid‐receptor‐1 (OPRM1). Neonatal rats received either four needle pricks per day in the left hind‐paw from postnatal day 0–7 as a model of procedural pain in infancy. Control pups were handled in the same way but were instead tactile stimulated, or were left undisturbed. At the age of 8 weeks, all animals received an ipsilateral hind‐paw incision as a model for post‐operative pain, and mechanical sensitivity was tested at multiple time‐points. Before, and 1 or 5 days post‐incision, spinal cord tissue was collected for immunostaining of opioid receptor OPRM1. Semi‐quantitative immunocytochemical analysis of superficial laminae in lumbar spinal dorsal horn revealed that: (1) early life repetitive tactile or noxious procedures do not alter baseline levels of OPRM1 staining intensity and (2) early life repetitive tactile or noxious procedures lead to a decrease in OPRM1 staining intensity 5 days after incision in adulthood compared to undisturbed controls. We conclude that early life repetitive tactile or noxious procedures affect the intensity of OPRM1‐immunoreactivity in the lumbar superficial spinal cord dorsal horn after adulthood injury, without affecting baseline intensity. © 2018 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc. Develop Neurobiol 78: 417–426, 2018
Timing of precipitation in an arid environment: Effects on population performance of a large herbivore
Authors: Heffelfinger Levi J. , Stewart Kelley M. , Bush Anthony P. , Sedinger James S. , Darby Neal W. , Bleich Vernon C. 
Published: February 2018

AbstractClimate models predict that shifts in temperature and precipitation patterns are likely to occur across the globe. Changing climate will likely have strong effects on arid environments as a result of increased temperatures, increasing frequency and intensity of droughts, and less consistent pulses of rainfall. Therefore, understanding the link between patterns of precipitation, temperature, and population performance of species occupying these environments will continue to increase in importance as climatic shifts occur within these natural ecosystems. We sought to evaluate how individual, maternal, population, and environmental, particularly temperature and precipitation, level factors influence population performance of a large herbivore in an arid environment. We used mule deer (Odocoileus hemionus) as a representative species and quantified juvenile survival to test hypotheses about effects of environmental factors on population performance. Precipitation events occurring in mid‐ to late‐pregnancy (January–April) leading to spring green‐up, as indexed by normalized difference in vegetation index, had the strongest positive effect on juvenile survival and recruitment. In addition, larger neonates had an increased probability of survival. Our findings indicate that timing and amount of precipitation prior to parturition have strong influences on maternal nutritional condition, which was passed on to young. These results have important implications for understanding how animal populations may benefit from timing of precipitation during spring and prior to parturition, especially in arid environments.
What determines prey selection in owls? Roles of prey traits, prey class, environmental variables, and taxonomic specialization
Authors: Comay Orr , Dayan Tamar 
Published: February 2018

AbstractEcological theory suggests that prey size should increase with predator size, but this trend may be masked by other factors affecting prey selection, such as environmental constraints or specific prey preferences of predator species. Owls are an ideal case study for exploring how predator body size affects prey selection in the presence of other factors due to the ease of analyzing their diets from owl pellets and their widespread distributions, allowing interspecific comparisons between variable habitats. Here, we analyze various dimensions of prey resource selection among owls, including prey size, taxonomy (i.e., whether or not particular taxa are favored regardless of their size), and prey traits (movement type, social structure, activity pattern, and diet). We collected pellets of five sympatric owl species (Athene noctua, Tyto alba, Asio otus, Strix aluco, and Bubo bubo) from 78 sites across the Mediterranean Levant. Prey intake was compared between sites, with various environmental variables and owl species as predictors of abundance. Despite significant environmental impacts on prey intake, some key patterns emerge among owl species studied. Owls select prey by predator body size: Larger owls tend to feed on wider ranges of prey sizes, leading to higher means. In addition, guild members show both specialization and generalism in terms of prey taxa, sometimes in contrast with the expectations of the predator–prey body size hypothesis. Our results suggest that while predator body size is an important factor in prey selection, taxon specialization by predator species also has considerable impact.