bluuebunny/crossref_metadata_2025_split huggingface dataset:
Updated protocols for the detection of Sotatercept and Luspatercept in human serum
Authors: Reichel Christian , Gmeiner Günter , Walpurgis Katja , Thevis Mario 
Published: September 2018

AbstractWe recently published two protocols for the detection of Sotatercept (ACE‐011, ACVR2A‐Fc) and Luspatercept (ACE‐536, ACVR2B‐Fc) in human serum. Both methods used covalently immobilized antibodies on agarose beads for immunoprecipitation and SAR‐PAGE/Western blotting for detection. Disadvantages were the relatively high amount of antibody required per sample (10 μg) and the need of a secondary antibody for the final detection. The updated protocols overcome these limitations by antigen–antibody complex formation in solution followed by capture of the complex with anti‐antibody‐coated magnetic beads. They also omit the secondary antibody incubation step by usage of biotinylated primary antibodies, which can be directly incubated with streptavidin‐HRP. Thus, the new protocols are faster, simpler, and cheaper and offer comparable sensitivities.
Shifting the conservation paradigm: a synthesis of options for renovating nature under climate change
Authors: Prober Suzanne M. , Doerr Veronica A. J. , Broadhurst Linda M. , Williams Kristen J. , Dickson Fiona 
Published: September 2018

AbstractChanges in Earth's climate are accelerating, prompting increasing calls to ensure that investments in ecological restoration and nature conservation accommodate such changes. To acknowledge this need, we propose the term “ecological renovation” to describe ecological management and nature conservation actions that actively allow for environmental change. To evaluate and progress the development of ecological renovation and related intervention options in a climate change context, we reviewed the literature and established a typology of options that have been proposed. We explored how these options address emerging principles underpinning climate‐adapted conservation goals and whether the balance of approaches reflected in our typology is likely to be sufficient given expected rapid rates of climate change. Our typology recognizes a matrix of 23 intervention option types arranged on the basis of underpinning ecological mechanisms (“ameliorate changing conditions” or “build adaptive capacity”) on one axis, and the nature of the tools used to manipulate them (“low regrets” or “climate targeted”) on the other. Despite a burgeoning literature since 2008, we found that the majority of effort has consistently focused on low‐regrets adaptation approaches that aim to build adaptive capacity. This is in many ways desirable, but a paradigm shift enabling greater attention to climate‐targeted approaches is likely to be needed as climate change accelerates. When assessed against five emerging principles for setting nature conservation goals in a changing climate, only one option type could deliver to all five, and we identified a conflict between climate‐targeted options and “wildness” values that calls for deeper evaluation. Importantly, much of the inference in the 473 reviewed studies was drawn from ecological reasoning and modeling, with only 16% offering new empirical evidence. We also noted significant biases toward North America and Europe, forest ecosystems, trees, and vertebrates. To address these limitations and help shift the paradigm toward humans as “renovators” rather than “restorers” of a prior world, we propose that ecological researchers contribute by (1) informing societal discourse toward adapting nature conservation goals to climate change, (2) adjusting and upscaling conservation planning to accommodate this suite of climate‐adapted goals, and (3) reconceptualizing experimental approaches to increase empirical evidence and expedite innovation of tools to address change.
The relationship between invader abundance and impact
Authors: Sofaer Helen R. , Jarnevich Catherine S. , Pearse Ian S. 
Published: September 2018

AbstractThe impacts of invasive species generally increase with their abundance, but the form of invader abundance–impact relationships remain poorly described. We highlight the utility of abundance–impact curves for three questions. First, abundance–impact relationships can clarify whether prevention and management should focus on the species likely to become abundant or those likely to cause large impacts per individual. Second, comparing abundance–impact relationships between native and exotic species can reveal any systematic differences in their effects on ecological systems. Third, identifying any thresholds in the relationship between invader impact and abundance can be used to select management targets and design invasive species control strategies. With increasing extent and resolution of datasets of invasive organisms worldwide, we now have the opportunity to explore in detail the form and context dependence of the abundance–impact relationship. Doing so provides opportunities to improve the prediction of invader impact, to better understand the differences between exotic and resident organisms, and to scale the impacts of invasive species from localities to ranges.
Statistical harmonization and uncertainty assessment in the comparison of satellite and radiosonde climate variables
Authors: Finazzi F. , Fassò A. , Madonna F. , Negri I. , Sun B. , Rosoldi M. 
Published: September 2018

AbstractSatellite product validation is a key to ensure the delivery of quality products for climate and weather applications. To do this, a fundamental step is the comparison with other instruments, such as radiosonde. This is especially true for essential climate variables such as temperature and humidity.Thanks to a functional data representation, this paper uses a likelihood‐based approach that exploits the measurement uncertainties in a natural way. In particular, the comparison of temperature and humidity radiosonde measurements collected within the network of the Universal Rawinsonde Observation Program (RAOB) and the corresponding atmospheric profiles derived from the infrared atmospheric sounding interferometer aboard MetOp‐A and MetOp‐B satellites is developed with the aim of understanding the vertical smoothing mismatch uncertainty.Moreover, conventional RAOB functional data representation is assessed by means of a comparison with radiosonde reference measurements given by the Global Climate Observing System (GCOS) Reference Upper‐Air Network (GRUAN), which provides high‐resolution fully traceable radio‐sounding profiles. In this way, the uncertainty related to coarse vertical resolution, or sparseness, of the conventional RAOB is assessed.It has been found that the uncertainty of vertical smoothing mismatch averaged along the profile is 0.50 K for temperature and 0.16 g/kg for water‐vapor mixing ratio. Moreover, the uncertainty related to RAOB sparseness, averaged along the profile, is 0.29 K for temperature and 0.13 g/kg for water‐vapor mixing ratio.
The Validity of Inferences From Locally Developed Assessments Administered Globally
Authors: Oliveri María Elena , Lawless René 
Published: September 2018

AbstractIn this paper, we first examine the challenges of score comparability associated with the use of assessments that are exported. By exported assessments, we mean assessments that are developed for domestic use and are then administered in other countries in either the same or a different language. Second, we provide suggestions to better support their valid and fair use. We illustrate these issues in the context of higher education assessments that are designed to serve different purposes—inform admissions decisions and assess student learning outcomes within one country (e.g., the United States) that are later used in other countries. In higher education, the use of exported assessments is on the rise due to increases in globalization, student mobility, and cross‐national comparisons of student achievement. An increase in the use of exported assessments leads to more diverse test‐taker populations and requires special attention due to possible sources of construct‐irrelevant variance, which may threaten the score‐based inferences made for various populations. Irrelevant sources of variance may emerge due to differences in opportunity to learn, curricular exposure, and lack of familiarity with the cultural references used in the assessments that are exported.
KMT2A (MLL) rearrangements observed in pediatric/young adult T‐lymphoblastic leukemia/lymphoma: A 10‐year review from a single cytogenetic laboratory
Authors: Peterson Jess F. , Baughn Linda B. , Pearce Kathryn E. , Williamson Cynthia M. , Benevides Demasi Jonna C. , Olson Renee M. , Goble Tony A. , Meyer Reid G. , Greipp Patricia T. , Ketterling Rhett P. 
Published: September 2018

AbstractT‐lymphoblastic leukemia/lymphoma (T‐ALL/LBL) accounts for approximately 15% of pediatric and 25% of adult ALL. While the underlying frequency of KMT2A (MLL) gene rearrangements has been identified in approximately 4‐8% of T‐ALL/LBL cases, a paucity of literature is available to characterize further the KMT2A rearrangements in pediatric/young adult T‐ALL/LBL. A 10‐year retrospective review was performed to identify KMT2A rearrangements in specimens sent for T‐ALL/LBL fluorescence in situ hybridization studies in patients under the age of 30 years. Of 806 T‐ALL/LBL FISH studies performed on unique individuals, 27 (3.3%) harbored KMT2A rearrangements. Nineteen patients were male and eight were female (M:F ratio, 2.4:1) with ages ranging from 1 to 20 years (mean 12, median 12). Of the 27 cases, nine (33%) had KMT2A/MLLT1 fusions, eight (30%) had KMT2A/AFDN fusions, two (7%) had KMT2A/ELL fusions, and one (4%) had a KMT2A/MLLT10 fusion. In addition, five (19%) had KMT2A rearrangements with unidentified gene fusion partners and two (7%) had 3’KMT2A deletions. Our results indicate that MLLT1 and AFDN account for the majority (63%) of KMT2A gene partners in pediatric/young adult T‐ALL/LBL, while no KMT2A/AFF1 or KMT2A/MLLT3 fusions were observed despite their common identification in B‐ALL and acute myeloid leukemia, respectively. In addition to diagnostic and prognostic value, detecting specific KMT2A fusions may also be of clinical importance in the era of targeted therapies.
Natives as international medical graduates: A nationwide analysis in Taiwan
Authors: Chu Feng‐Yuan , Chao Yin‐Mei , Chou Li‐Fang , Chen Tzeng‐Ji 
Published: September 2018

SummaryIntroductionInternational medical graduates (IMGs) play an important role in many Western countries because of globalization and physician shortages. While the IMGs investigated in most studies were immigrants, few studies have considered the situation in which people native to a given country have studied medicine abroad and then returned to practice in their home country. To illustrate that situation, our study aimed to investigate practicing IMGs in Taiwan by comparing practicing physicians' nationalities to the countries in which the medical schools the IMGs graduated from are located.MethodsData were obtained from the annual official statistics released by the Taiwan Medical Association from 1998 to 2017.ResultsThe number of practicing IMGs in Taiwan increased from 834 (3.1% of 26,991 physicians) in 1998 to 1,733 (3.7% of 46,452) in 2017. Their medical schools were distributed across 37 countries, with graduates of schools in the Philippines (n = 550), Poland (n = 420), and Myanmar (n = 364) accounting for 77.0% of all practicing IMGs in 2017. However, only 29, 0, and 253 physicians were themselves Filipinos, Polish, and Myanmarese, respectively.ConclusionMost of the practicing IMGs in Taiwan are native Taiwanese. The real impact of IMGs in health policy‐making and the existing quota system of admissions to medical schools thus deserve further investigations.
Upregulated long noncoding RNA LINC01296 indicates a dismal prognosis for pancreatic ductal adenocarcinoma and promotes cell metastatic properties by affecting EMT
Authors: Yuan Qihua , Zhang Yuxia , Feng Lijun , Jiang Yuehong 
Published: September 2018

AbstractBackgroundPancreatic ductal adenocarcinoma (PDAC) is a fatal disease that responds poorly to chemotherapy and radiotherapy and whose incidence has increased worldwide. Long noncoding RNAs have been demonstrated to play important roles in cancer initiation and progression. Long intergenic non‐coding RNA 01296 (LINC01296) has been reported to be upregulated in several malignancies, but the clinical relevance and biological role of LINC01296 in PDAC are still unclear.MethodsRT‐qPCR was performed to evaluate the expression of LINC01296 in 85 pared PDAC tissue samples and a panel of PDAC cell lines. The clinical value and prognostic role of LINC01296 in patients with PDAC were further explored. Furthermore, we explored the functional roles of LINC01296 depletion in PANC‐1 and SW1990 cells, including cell proliferation, apoptosis, migration, invasion, and epithelial‐to‐mesenchymal transition (EMT).ResultsLINC01296 was enhanced in PDAC tissues and cell lines, and this overexpression was correlated with advanced tumor stages and positive lymph node metastasis in patients with PDAC. In addition, upregulation of LINC01296 was an independent prognostic predictor for patients with PDAC after surgery. Moreover, silencing of LINC01296 followed by treatment with small interfering RNAs suppressed cell proliferation and promoted cell apoptosis by affecting the Bcl‐2/caspase‐3 pathway. Importantly, LINC01296 attenuation impaired the migratory and invasive potential partly by reversing EMT.ConclusionsOverall, our work may help to develop a novel prognostic biomarker and therapeutic target for PDAC.
Microarray‐based analysis of whole‐genome DNA methylation profiling in early detection of breast cancer
Authors: Li Shao‐Ying , Wu Hua‐Cong , Mai Hui‐Fen , Zhen Jian‐Xin , Li Gui‐Sen , Chen Shao‐Jun 
Published: September 2018

AbstractEmerging evidence indicated that changes in DNA methylation early in breast cancer (BC) development might be clinically relevant for therapeutic decisions. Through analysis of whole‐genome gene expression microarray and DNA methylation microarray, we explored genes with abnormal DNA methylation in BC for early detection. Firstly, human BC tissues and adjacent non‐cancerous tissues were collected from nine BC patients. Gene expression microarray sequencing was conducted for identifying differentially expressed genes and DNA methylation microarray sequencing for differentially methylated genes in BC. Differentially expressed genes and methylated genes in BC were further explored using the Cancer Genome Atlas database. The correlation between DNA methylation and gene expression was illustrated by multiple comparisons. In other 60 clinical samples, methylation specific polymerase chain reaction (PCR) and reverse transcription quantitative PCR were applied for the methylation of HOXA4 and IGF1 genes in BC and adjacent non‐cancerous tissues. In total, 1680 upregulated genes and 1249 downregulated genes were determined in BC. Chromosome 16 and 17 showed more differentially methylated genes, and DNA methylation level was increased in BC tissues in each gene region. Chromosome 19 showed more differentially methylated genes, and DNA methylation level was increased in BC tissues in the exoniensis 1, untranslated region‐5 and transcriptional start site 200 gene regions. In other 60 clinical samples, HOXA4 and IGF1 in BC tissues presented increased DNA methylation and decreased gene expression in BC. MCF7 cells treated with RG108 showed decreased HOXA4 and IGF1 expressions. It was estimated that HOXA4 and IGF1 were identified with increased DNA methylation and decreased gene expression in BC, which may serve as biomarkers in early BC detection.
LINC00657 expedites neuropathic pain development by modulating miR‐136/ZEB1 axis in a rat model
Authors: Shen Fujin , Zheng Hongyun , Zhou Limei , Li Wei , Zhang Yang , Xu Xuexian 
Published: September 2018

AbstractLong non‐coding RNAs (lncRNAs) are involved in the progression of several diseases. The interactions among lncRNAs, microRNA (miRNAs) or their targeting genes are reported to play crucial roles in the development of diseases. LINC00657 is observed to be upregulated in several cancers. However, the biological role of LINC00657 in neuropathic pain progress is unclear. Hence, in our study, we aimed to investigate the function of LINC00657 in neuropathic pain development. A chronic constriction injury (CCI) rat model was established, and we found that LINC00657 was greatly increased in CCI rats associated with a decrease of miR‐136. Inhibition of LINC00657 suppressed neuropathic pain via alleviating mechanical and thermal hyperalgesia. In addition, miR‐136 overexpression can also inhibit the neuropathic pain development. MiR‐136 was predicted to serve as a miRNA target of LINC00657, and dual‐luciferase reporter assay confirmed the correlation between LINC00657 and miR‐136. Moreover, we observed that the decrease of LINC00657 was able to inhibit the neuroinflammation of CCI rats by targeting expression of cyclooxygenase‐2, tumor necrosis factor‐α and interleukin‐1β while miR‐136 inhibitors reversed this phenomenon. Next, by using bioinformatics analysis, ZEB1 was predicted as a direct target of miR‐136, and miR‐136 could negatively modulate ZEB1 expression. Besides these, ZEB1 was remarkably increased in the CCI rats. Knockdown of ZEB1 can inhibit neuropathic pain development, while miR‐136 inhibitors can reverse it. In conclusion, it was implied that LINC00657 can induce the neuropathic pain development via regulating miR‐136/ZEB1 axis.
Nobiletin inhibits hypoxia‐induced epithelial‐mesenchymal transition in renal cell carcinoma cells
Authors: Liu Feng , Zhang Siqi , Yin Min , Guo Lihua , Xu Mingzhu , Wang Yonggang 
Published: September 2018

AbstractHypoxia is a universal characteristic of solid tumor and involving cancer metastasis via epithelial‐mesenchymal transition (EMT). Nobiletin (3′,4′,5,6,7,8‐hexamethoxyflavone), a dietary polymethoxylated flavonoid found in citrus fruits, has been reported to have anticancer effects. However, the possible role of nobiletin in renal cell carcinoma (RCC) remains unclear. Thus, the aim of this study was to identify the effect of nobiletin on hypoxia‐induced EMT in RCC cells. We found that nobiletin significantly inhibited the migration and invasion induced by hypoxia in RCC cells. In addition, nobiletin reversed the hypoxia‐induced EMT process in RCC cells. Furthermore, nobiletin suppressed the activation of NF‐κB and Wnt/β‐catenin signaling pathways in hypoxia‐stimulated RCC cells. In conclusion, these findings demonstrate that nobiletin inhibits hypoxia‐induced EMT in human RCC cells via the inactivation of the NF‐κB and Wnt/β‐catenin signaling pathways.
CCN1 induces apoptosis in esophageal adenocarcinoma through p53‐dependent downregulation of survivin
Authors: Dang Tong , Modak Cristina , Meng Xiemei , Wu Jinbao , Narvaez Reinier , Chai Jianyuan 
Published: September 2018

AbstractMany cancer drugs have been developed to control tumor growth by inducing cancer cell apoptosis. However, several intracellular barriers could fail this attempt. One of these barrier is high expression of survivin. Survivin can interfere caspase activation and thereby abort apoptosis. In this study, we found that CCN1 suppressed the survivin expression in tumor cells of esophageal adenocarcinoma (EAC) and thus allowed apoptosis to finish. Furthermore, we demonstrated that this downregulation was dependent on p53 phosphorylation at Ser20, and CCN1 induced EAC cell apoptosis through the activation of p53.
Microvesicles‐mediated communication between endothelial cells modulates, endothelial survival, and angiogenic function via transferring of miR‐125a‐5p
Authors: Pan Qunwen , Ma Chunlian , Wang Yan , Wang Jinju , Zheng Jieyi , Du Donghui , Liao Xiaorong , Chen Yusen , Chen Yanfang , Bihl Ji , Chen Can , Yang Yi , Ma Xiaotong 
Published: September 2018

AbstractEndothelial cells (ECs) released microvesicles (EMVs) could modulate the functions of target cells by transferring their microRNAs (miRs). We have reported that miR‐125a‐5p protected EC function. In this study, we determined whether EMVs provided beneficial effects on ECs by transferring miR‐125a‐5p. Human brain microvessel ECs were transfected with miR‐125a‐5p mimic or miR‐125a‐5p short hairpin RNA to obtain miR‐125a‐5p overexpressing ECs and miR‐125a‐5p knockdown ECs, and their derived EMVs. For the functional study, ECs or hypoxia/reoxygenation injured ECs were coincubated with various EMVs. The survival and angiogenic function of ECs were measured. Western blot and quantitative real time polymerase chain reaction (qRT‐PCR) were used for measuring the levels of phosphoinositide 3‐kinase (PI3K), phosphorylation‐Akt (p‐Akt)/Akt, p‐endothelial nitric oxide synthase (p‐eNOS), cleaved caspase‐3, and miR‐125a‐5p. PI3K inhibitor was used for pathway analysis. EMVs promoted the proliferation, migration, and tube formation ability of ECs, and alleviated the apoptotic rate of ECs. These effects were associated by an increase in p‐Akt/Akt and p‐eNOS, and a decrease in cleaved caspase‐3 could be abolished by LY294002. Overexpression or downregulation of miR‐125a‐5p in EMVs promoted or inhibited those effects of EMVs. EMVs could enhance the survival and angiogenic function of ECs via delivering miR‐125a‐5p to modulate the expression of PI3K/Akt/eNOS pathway and caspase‐3.
Association between miR‐34b/c rs4938723 polymorphism and risk of cancer: An updated meta‐analysis of 27 case‐control studies
Authors: Hashemi Mohammad , Moazeni‐Roodi Abdolkarim , Bahari Gholamreza , Taheri Mohen , Ghavami Saeid 
Published: September 2018

AbstractSeveral studies investigated the association between miR‐34b/c rs4938723 polymorphism and the risk of several human cancers, but the findings remain inconclusive. To evaluate the impact of miR‐34b/c rs4938723 on cancer risk, we performed a meta‐analysis on all available studies including 12 361 cancer cases and 14 270 controls. Eligible studies were identified by searching PubMed, Web of Science, Scopus, and Google scholar databases. Pooled odds ratios with 95% confidence intervals were calculated in codominant, dominant, recessive, overdominant, and allele models to quantitatively estimate the association. The overall findings showed no significant association between miR‐34b/c rs4938723 polymorphism and cancer risk in codominant, dominant, recessive, overdominant, and allele inheritance model. However, in stratified analysis by cancer types, the rs4938723 polymorphism significantly increased the risk of gastrointestinal cancer, hepatocellular carcinoma. In addition, the rs4938723 polymorphism was associated with decreased risk of esophageal squamous cell carcinoma, colorectal cancer, and acute lymphoblastic leukemia. The findings did not support an association between rs4938723 variant and digestive tract as well as gastric cancer. In summary, the findings of this meta‐analysis indicated that the miR‐34b/c rs4938723 polymorphism might be associated with some cancer development. Larger and well‐designed studies are necessary to estimate this association in detail.