bluuebunny/crossref_metadata_2025_split huggingface dataset:
Negative plasma Epstein-Barr virus DNA nasopharyngeal carcinoma in an endemic region and its influence on liquid biopsy screening programmes
Authors: Nicholls John Malcolm , Lee Victor Ho-Fun , Chan Sik-Kwan , Tsang Ka-Chun , Choi Cheuk-Wai , Kwong Dora Lai-Wan , Lam Ka-On , Chan Sum-Yin , Tong Chi-Chung , So Tsz-Him , Leung To-Wai , Luk Mai-Yee , Khong Pek-Lan , Lee Anne Wing-Mui 
Published: September 2019

Abstract

Background
Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) in endemic regions may have undetectable plasma EBV DNA.

Methods
We prospectively recruited 518 patients with non-metastatic NPC and measured their pre-treatment plasma EBV DNA. The stage distribution and prognosis between pre-treatment plasma EBV DNA-negative (0–20 copies/ml) and EBV DNA-positive (>20 copies/ml) patients following radical treatment were compared.

Results
Seventy-eight patients (15.1%) were plasma EBV DNA-negative, and 62 in this subset (12.0%) had 0 copy/ml. Only 23/78 (29.5%) plasma EBV DNA-negative patients with advanced NPC (stage III-IVA) had strong EBV encoded RNA (EBER) positivity (score 3) in their tumours compared to 342/440 (77.7%) EBV DNA-positive patients of the same stages (p < 0.001). Though EBV DNA-negative patients had more early-stage disease (p < 0.001) and smaller volumes of the primary tumour and the positive neck nodes (p < 0.001), they had similar 5-year overall survival and cancer-specific survival to those EBV DNA-positive counterparts by stage. Similar results were also seen when plasma EBV DNA cut-off was set at 0 copy/ml.

Conclusions
Patients with low-volume NPC may not be identified by plasma/serum tumour markers and caution should be taken in its utility as a screening tool for NPC even in endemic regions.

Clinical trial registration
Clinicaltrials.gov Identifier: NCT02476669.
Evidence of necroptosis in osteoarthritic disease: investigation of blunt mechanical impact as possible trigger in regulated necrosis
Authors: Riegger Jana , Brenner Rolf E. 
Published: September 2019

AbstractJoint injuries are highly associated with cell death and development of posttraumatic osteoarthritis (PTOA). The present study focused on necroptosis as a possible modality of chondrocyte death after cartilage trauma and its relevance in OA disease in general. For this purpose, apoptosis- and necroptosis-associated markers were determined in highly degenerated (ICRS ≥ 3) as well as macroscopically intact cartilage tissue (ICRS ≤ 1) by means of real-time PCR and immunohistochemistry (IHC). Moreover, influence of blunt trauma and/or stimulation with cycloheximide (CHX), TNF-a, and caspase-inhibitor zVAD were investigated in cartilage explants (ICRS ≤ 1). Further characterization of necroptosis was performed in isolated chondrocytes. We found that gene expression levels of RIPK3 (4.2-fold, P < 0.0001) and MLKL (2.7-fold, P < 0.0001) were elevated in highly degenerated cartilage tissue, which was confirmed by IHC staining. After ex vivo trauma and/or CHX/TNF stimulation, addition of zVAD further enhanced expression of necroptosis-related markers as well as release of PGE2 and nitric oxide, which was in line with increased cell death and subsequent release of intracellular HMGB1 and dsDNA in CHX/TNF stimulated chondrocytes. However, trauma and/or chemically induced cell death and subsequent release of pro-inflammatory mediators could be largely attenuated by RIPK1-inhibitor necrostatin 1 or antioxidant N-acetylcysteine. Overall, the study provided clear evidence of necroptotic cell death in OA disease. Moreover, a possible link between cartilage injury and necroptotic processes was found, depending on oxidative stress and cytokine release. These results contribute to further understanding of cell death in PTOA and development of novel therapeutic approaches.
PICOT binding to chromatin-associated EED negatively regulates cyclin D2 expression by increasing H3K27me3 at the CCND2 gene promoter
Authors: Pandya Pinakin , Jethva Minesh , Rubin Eitan , Birnbaum Ramon Y. , Braiman Alex , Isakov Noah 
Published: September 2019

AbstractProtein kinase C (PKC)-interacting cousin of thioredoxin (PICOT; also termed glutaredoxin 3 (Grx3; Glrx3)) is a ubiquitous protein that can interact with the embryonic ectoderm development (EED) protein via each of its two C-terminal PICOT/Grx homology domains. Since EED is a Polycomb-Group protein and a core component of the polycomb repressive complex 2 (PRC2), we tested the involvement of PICOT in the regulation of PRC2-mediated H3 lysine 27 trimethylation (H3K27me3), transcription and translation of selected PRC2 target genes. A fraction of the cellular PICOT protein was found in the nuclei of leukemia cell lines, where it was associated with the chromatin. In addition, PICOT coimmunoprecipitated with chromatin-residing EED derived from Jurkat and COS-7 cell nuclei. PICOT knockdown led to a reduced H3K27me3 mark and a decrease in EED and EZH2 at the CCND2 gene promoter. In agreement, PICOT-deficient T cells exhibited a significant increase in CCND2 mRNA and protein expression. Since elevated expression levels of PICOT were reported in several different tumors and correlated in the current studies with decreased transcription and translation of the CCND2 gene, we tested whether this opposite correlation exists in human cancers. Data from the Cancer Genome Atlas (TCGA) database indicated statistically significant negative correlation between PICOT and CCND2 in eight different human tumors where the highest correlation was in lung (p = 8.67E−10) and pancreatic (p = 1.06E−5) adenocarcinoma. Furthermore, high expression of PICOT and low expression of CCND2 correlated with poor patient survival in five different types of human tumors. The results suggest that PICOT binding to chromatin-associated EED modulates the H3K27me3 level at the CCND2 gene promoter which may be one of the potential mechanisms for regulation of cyclin D2 expression in tumors. These findings also indicate that a low PICOT/CCND2 expression ratio might serve as a good predictor of patient survival in selected human cancers.
TA*p63 and GTAp63 achieve tighter transcriptional regulation in quality control by converting an inhibitory element into an additional transactivation domain
Authors: Pitzius Susanne , Osterburg Christian , Gebel Jakob , Tascher Georg , Schäfer Birgit , Zhou Huiqing , Münch Christian , Dötsch Volker 
Published: September 2019

AbstractThe p53 homolog p63 plays important roles in development of epithelial tissues and quality control in germ cells. These two functions are executed by two distinct isoforms of p63. They are created by different promotors resulting in isoforms having either an N-terminal transactivation domain (TAp63) or a truncated form (ΔNp63). In addition to these two N-terminal isoforms a third one with an even longer N-terminus, named TA*p63, has been found. A fourth N-terminal isoform, GTAp63, that closely resembles TA*p63 was discovered in male germ cells where it is involved in genetic quality control. Here, we characterize TA*p63α and GTAp63α and show that their N-terminal extensions stabilize the closed and only dimeric conformation adopted by the shorter TAp63α protein. Both proteins can be activated by the two kinases Chk2 and CK1 resulting in the open tetrameric state. In this conformation, the N-terminal extension acts as an additional transactivation domain enhancing transcriptional activity. Through this mechanism, the difference in transcriptional activity between the repressed and the active state of the protein gets enhanced relative to TAp63α. Finally, we show by mass spectrometry that TA*p63α is expressed in the breast cancer cell line Sum159 at the protein level together with mutant p53. Upon doxorubicin treatment, TA*p63α gets activated, providing a potential new tool to fight cancer.
Estimating cumulative point prevalence of rare diseases: analysis of the Orphanet database
Authors: Nguengang Wakap Stéphanie , Lambert Deborah M. , Olry Annie , Rodwell Charlotte , Gueydan Charlotte , Lanneau Valérie , Murphy Daniel , Le Cam Yann , Rath Ana 
Published: September 2019

Abstract
Rare diseases, an emerging global public health priority, require an evidence-based estimate of the global point prevalence to inform public policy. We used the publicly available epidemiological data in the Orphanet database to calculate such a prevalence estimate. Overall, Orphanet contains information on 6172 unique rare diseases; 71.9% of which are genetic and 69.9% which are exclusively pediatric onset. Global point prevalence was calculated using rare disease prevalence data for predefined geographic regions from the ‘Orphanet Epidemiological file’ (http://www.orphadata.org/cgi-bin/epidemio.html). Of the 5304 diseases defined by point prevalence, 84.5% of those analysed have a point prevalence of <1/1 000 000. However 77.3–80.7% of the population burden of rare diseases is attributable to the 4.2% (n = 149) diseases in the most common prevalence range (1–5 per 10 000). Consequently national definitions of ‘Rare Diseases’ (ranging from prevalence of 5 to 80 per 100 000) represent a variable number of rare disease patients despite sharing the majority of rare disease in their scope. Our analysis yields a conservative, evidence-based estimate for the population prevalence of rare diseases of 3.5–5.9%, which equates to 263–446 million persons affected globally at any point in time. This figure is derived from data from 67.6% of the prevalent rare diseases; using the European definition of 5 per 10 000; and excluding rare cancers, infectious diseases, and poisonings. Future registry research and the implementation of rare disease codification in healthcare systems will further refine the estimates.
Adaptive signals of flowering time pathways in wild barley from Israel over 28 generations
Authors: Qian Chaoju , Yan Xia , Shi Yong , Yin Hengxia , Chang Yuxiao , Chen Jun , Ingvarsson Pär K. , Nevo Eviatar , Ma Xiao-Fei 
Published: September 2019

AbstractFlowering time is one of the most critical traits for plants’ life cycles, which is influenced by various environment changes, such as global warming. Previous studies have suggested that to guarantee reproductive success, plants have shifted flowering times to adapt to global warming. Although many studies focused on the molecular mechanisms of early flowering, little was supported by the repeated sampling at different time points through the changing climate. To fully dissect the temporal and spatial evolutionary genetics of flowering time, we investigated nucleotide variation in ten flowering time candidate genes and nine reference genes for the same ten wild-barley populations sampled 28 years apart (1980–2008). The overall genetic differentiation was significantly greater in the descendant populations (2008) compared with the ancestral populations (1980); however, local adaptation tests failed to detect any single-nucleotide polymorphism (SNP)/indel under spatial-diversifying selection at either time point. By contrast, the WFABC (Wright–Fisher ABC-based approach) that detected 54 SNPs/indels was under strong selection during the past 28 generations. Moreover, all these 54 alleles were segregated in the ancestral populations, but fixed in the descendent populations. Among the top ten SNPs/indels, seven were located in genes ofFT1(FLOWERING TIME LOCUS T 1),CO1(CONSTANS-LIKE PROTEIN 1), andVRN-H2(VERNALIZATION-H2), which have been documented to be associated with flowering time regulation in barley cultivars. This study might suggest that all ten populations have undergone parallel evolution over the past few decades in response to global warming, and even an overwhelming local adaptation and ecological differentiation.
Characterization of suprathermal electrons inside a laser accelerated plasma via highly-resolved K⍺-emission
Authors: Šmíd M. , Renner O. , Colaitis A. , Tikhonchuk V. T. , Schlegel T. , Rosmej F. B. 
Published: September 2019

AbstractSuprathermal electrons are routinely generated in high-intensity laser produced plasmas via instabilities driven by non-linear laser-plasma interaction. Their accurate characterization is crucial for the performance of inertial confinement fusion as well as for performing experiments in laboratory astrophysics and in general high-energy-density physics. Here, we present studies of non-thermal atomic states excited by suprathermal electrons in kJ-ns-laser produced plasmas. Highly spatially and spectrally resolved X-ray emission from the laser-deflected part of the warm dense Cu foil visualized the hot electrons. A multi-scale two-dimensional hydrodynamic simulation including non-linear laser-plasma interactions and hot electron propagation has provided an input for ab initio non-thermal atomic simulations. The analysis revealed a significant delay between the maximum of laser pulse and presence of suprathermal electrons. Agreement between spectroscopic signatures and simulations demonstrates that combination of advanced high-resolution X-ray spectroscopy and non-thermal atomic physics offers a promising method to characterize suprathermal electrons inside the solid density matter.
A molecular movie of ultrafast singlet fission
Authors: Schnedermann Christoph , Alvertis Antonios M. , Wende Torsten , Lukman Steven , Feng Jiaqi , Schröder Florian A. Y. N. , Turban David H. P. , Wu Jishan , Hine Nicholas D. M. , Greenham Neil C. , Chin Alex W. , Rao Akshay , Kukura Philipp , Musser Andrew J. 
Published: September 2019

AbstractThe complex dynamics of ultrafast photoinduced reactions are governed by their evolution along vibronically coupled potential energy surfaces. It is now often possible to identify such processes, but a detailed depiction of the crucial nuclear degrees of freedom involved typically remains elusive. Here, combining excited-state time-domain Raman spectroscopy and tree-tensor network state simulations, we construct the full 108-atom molecular movie of ultrafast singlet fission in a pentacene dimer, explicitly treating 252 vibrational modes on 5 electronic states. We assign the tuning and coupling modes, quantifying their relative intensities and contributions, and demonstrate how these modes coherently synchronise to drive the reaction. Our combined experimental and theoretical approach reveals the atomic-scale singlet fission mechanism and can be generalized to other ultrafast photoinduced reactions in complex systems. This will enable mechanistic insight on a detailed structural level, with the ultimate aim to rationally design molecules to maximise the efficiency of photoinduced reactions.
Highly selective detection of methanol over ethanol by a handheld gas sensor
Authors: van den Broek J. , Abegg S. , Pratsinis S. E. , Güntner A. T. 
Published: September 2019

AbstractMethanol poisoning causes blindness, organ failure or even death when recognized too late. Currently, there is no methanol detector for quick diagnosis by breath analysis or for screening of laced beverages. Typically, chemical sensors cannot distinguish methanol from the much higher ethanol background. Here, we present an inexpensive and handheld sensor for highly selective methanol detection. It consists of a separation column (Tenax) separating methanol from interferants like ethanol, acetone or hydrogen, as in gas chromatography, and a chemoresistive gas sensor (Pd-doped SnO2 nanoparticles) to quantify the methanol concentration. This way, methanol is measured within 2 min from 1 to 1000 ppm without interference of much higher ethanol levels (up to 62,000 ppm). As a proof-of-concept, we reliably measure methanol concentrations in spiked breath samples and liquor. This could enable the realization of highly selective sensors in emerging applications such as breath analysis or air quality monitoring.
Montmorillonite immobilized Fe/Ni bimetallic prepared by dry in-situ hydrogen reduction for the degradation of 4-Chlorophenlo
Authors: Zhang Shuo-Shuo , Yang Ning , Zhuang Xuming , Ren Liying , Natarajan Vinothkumar , Cui Zhaojie , Si Hongyu , Xin Xiaohan , Ni Shou-Qing , Zhan Jinhua 
Published: September 2019

AbstractThis study puts forward a new way to produce montmorillonite immobilized bimetallic nickel-iron nanoparticles by dry in-situ hydrogen reduction method in the non-liquid environment, which effectively inhibits the oxidation of iron and nickel during the synthesis process and improves the reactivity of the material. The degradation of 4-Chlorophenol (4-CP) was investigated to examine the catalytic activity of the material. The morphology and crystal properties of the montmorillonite-templated Fe/Ni bimetallic particles were explored by using scanning electron microscopy, transmission electron microscopy, X-ray diffraction studies, and energy dispersive X-ray spectroscopy analysis. Results suggest that Fe and Ni particles were homogeneously dispersed on the montmorillonite. The optimization of Ni content and reduction temperature over the degradation of 4-CP was also studied. The introduction of Ni intensely improved the degradation of 4-CP and reached over 90% when Ni content was 28.5%. The degradation rate increased significantly with the increase of reduction temperature and showed maximum activity at the reduction tempreature of 800 °C. This study offers a new method to fabricate montmorillonite immobilized Fe/Ni bimetallic nanoparticles in the non-liquid environment and the composites exhibited high degradation activity to chlorinated organic compounds.
Open-label placebos reduce test anxiety and improve self-management skills: A randomized-controlled trial
Authors: Schaefer Michael , Denke Claudia , Harke Rebecca , Olk Nina , Erkovan Merve , Enge Sören 
Published: September 2019

AbstractTest anxiety is a condition in which people experience extreme distress and anxiety before and in test situations. It affects up to 40 percent of all students. Conventional treatment includes both medication and psychotherapy, but studies also demonstrated that placebos affect anxiety symptoms. Although in the traditional understanding placebos need to be administered in a concealed way, intriguing new studies report that open-label placebos can be effective. Since prescription of fake pills involves ethical problems, open-label placebos may provide important new treatment possibilities. Here we report results of a pilot study examining whether open-label placebos may reduce test anxiety and improve self-management skills. 58 students participated in a two-group randomized controlled trial. Two weeks before an exam at the university participants received open-label placebos or no pills (control group). Participant – provider relationship and amount of contact time was held similar for all groups. After two weeks we found that test anxiety and self-management abilities (skills and resources) of the open-label placebo group were more improved than in the control group. Thus, our results seems to indicate that open-label placebos may reduce test anxiety and enhance self-management skills in students.
A FAM83A Positive Feed-back Loop Drives Survival and Tumorigenicity of Pancreatic Ductal Adenocarcinomas
Authors: Parameswaran Neetha , Bartel Courtney A. , Hernandez-Sanchez Wilnelly , Miskimen Kristy L. , Smigiel Jacob M. , Khalil Ahmad M. , Jackson Mark W. 
Published: September 2019

AbstractPancreatic ductal adenocarcinomas (PDAC) are deadly on account of the delay in diagnosis and dearth of effective treatment options for advanced disease. The insurmountable hurdle of targeting oncogene KRAS, the most prevalent genetic mutation in PDAC, has delayed the availability of targeted therapy for PDAC patients. An alternate approach is to target other tumour-exclusive effector proteins important in RAS signalling. The Family with Sequence Similarity 83 (FAM83) proteins are oncogenic, tumour-exclusive and function similarly to RAS, by driving the activation of PI3K and MAPK signalling. In this study we show that FAM83A expression is significantly elevated in human and murine pancreatic cancers and is essential for the growth and tumorigenesis of pancreatic cancer cells. Elevated FAM83A expression maintains essential MEK/ERK survival signalling, preventing cell death in pancreatic cancer cells. Moreover, we identified a positive feed-forward loop mediated by the MEK/ERK-activated AP-1 transcription factors, JUNB and FOSB, which is responsible for the elevated expression of oncogenic FAM83A. Our data indicates that targeting the MEK/ERK-FAM83A feed-forward loop opens up additional avenues for clinical therapy that bypass targeting of oncogenic KRAS in aggressive pancreatic cancers.
Evaluation and Validation of Reference Genes for Quantitative Real-Time PCR in Helopeltis theivora Waterhouse (Hemiptera: Miridae)
Authors: Wang Zheng , Meng Qianqian , Zhu Xi , Sun Shiwei , Gao Shengfeng , Gou Yafeng , Liu Aiqin 
Published: September 2019

AbstractHelopeltis theivora Waterhouse is a predominant sucking pest in many tropic economic crops, such as tea, cocoa and coffee. Quantitative real-time PCR (qRT-PCR) is one of the most powerful tools to analyze the gene expression level and investigate the mechanism of insect physiology at transcriptional level. Gene expression studies utilizing qRT-PCR have been applied to numerous insects so far. However, no universal reference genes could be used for H. theivora. To obtain accurate and reliable normalized data in H. theivora, twelve candidate reference genes were examined under different tissues, developmental stages and sexes by using geNorm, NormFinder, BestKeeper, Delta Ct and RefFinder algorithms, respectively. The results revealed that the ideal reference genes differed across the treatments, and the consensus rankings generated from stability values provided by these programs suggested a combination of two genes for normalization. To be specific, RPS3A and Actin were the best suitable reference genes for tissues, RPL13A and GAPDH were suitable for developmental stages, EF1α and RPL13A were suitable for sexes, and RPL13A and RPS3A were suitable for all samples. This study represents the first systematic analysis of reference genes for qRT-PCR experiments in H. theivora, and the results can provide a credible normalization for qRT-PCR data, facilitating transcript profiling studies of functional genes in this insect.
Arithmetic Skill May Refine the Performance of Individuals with High Math Anxiety, Especially in the Calculation Task: An ERP Study
Authors: Huang Bijuan , Zhao Xiaomeng , Li Hongxia , Yang Weixing , Cui Shuang , Gao Yaru , Si Jiwei 
Published: September 2019

AbstractAs a global phenomenon, the theme of math anxiety has received increasing attention. The present study aimed to investigate the relationship between math anxiety and performance and determine the role of arithmetic skill in two different tasks. Fifty-seven college freshmen were recruited to perform a comparison task and a calculation task. Only main effect of arithmetic skill was found on the behavioral level. In the comparison task, participants with high math anxiety (HMA) showed faster latencies and greater amplitudes of N1 and longer P3b latency relative to their counterparts with low math anxiety (LMA). Number, as a negative stimulus, occupied attentional resources and delayed the speed of cognitive processing for individuals with HMA. Furthermore, among those with HMA, individuals with high arithmetic skill showed larger amplitudes and shorter latencies of P2 compared with those with low airthmetic skill in the calculation task. Thus, arithmetic skill could refine the performance efficiency of individuals with HMA, especially in the calculation task. These results suggest that educational interventions emphasizing control of negative emotional responses to math stimuli will be more effective when considering different populations of mathematically competent individuals.