bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemoradiotherapy with extended nodal irradiation and/or erlotinib in locally advanced oesophageal squamous cell cancer: long-term update of a randomised phase 3 trial
Authors: Xie Congying , Jing Zhao , Luo Honglei , Jiang Wei , Ma Li , Hu Wei , Zheng Anping , Li Duojie , Ding Lingyu , Zhang Hongyan , Xie Conghua , Lian Xilong , Du Dexi , Chen Ming , Bian Xiuhua , Tan Bangxian , Xia Bing , Xie Ruifei , Liu Qing , Wang Lvhua , Wu Shixiu 
Published: September 2020

AbstractBackgroundTo report the long-term outcomes of a phase III trial designed to test two hypotheses: (1) elective nodal irradiation (ENI) is superior to conventional field irradiation (CFI), and (2) chemoradiotherapy plus erlotinib is superior to chemoradiotherapy in locally advanced oesophageal squamous cell cancer (ESCC).MethodsPatients with locally advanced ESCC were randomly assigned (1:1:1:1 ratio) to one of the four groups: A: radiotherapy adoption of ENI with two cycles of concurrent TP chemotherapy (paclitaxel and cisplatin) plus erlotinib; B: radiotherapy adoption of ENI with two cycles of concurrent TP; C: radiotherapy adoption of CFI with two cycles of concurrent TP plus erlotinib and D: radiotherapy adoption of CFI with two cycles of concurrent TP. A total of 60 Gy of radiation doses was delivered over 30 fractions. We explored the impact of epidermal growth factor receptor (EGFR) expression on the efficacy of erlotinib plus chemoradiotherapy.ResultsA total of 352 patients (88 assigned to each treatment group) were enrolled. The 5-year survival rates were 44.9%, 34.8%, 33.8% and 19.6% in groups A, B, C and D, respectively (P = 0.013). ENI significantly improved OS compared with standard CFI (median, 38.5 vs 22.6 months; HR, 0.74;P = 0.018). The addition of erlotinib significantly improved OS (median, 39.4 vs 27.4 months; HR, 0.75;P = 0.025). Patients with overexpressing EGFR treated with erlotinib had a better OS and PFS than those without erlotinib.ConclusionsConcurrent chemoradiotherapy with ENI and/or erlotinib improved long-term survival in locally advanced ESCC.Clinical trial registrationTrial registration: NCT00686114.
Bip inhibition in glioma stem cells promotes radiation-induced immunogenic cell death
Authors: Yang Wei , Xiu Zenghe , He Yuping , Huang Wenpeng , Li Yanyan , Sun Ting 
Published: September 2020

AbstractTumor regression in sites distant to the irradiated field are thought to be associated with emission of damage-associated molecular patterns (DAMPs) molecules and generation of immunogenic cell death (ICD). Glioma stem cells (GSCs) are resistant to high doses of radiation, and ultimately select the outgrowth of a more aggressive tumor. This study showed high-dose IR triggered fewer DAMPs molecules exposure and release in GSCs comparing to matched non-GSCs. Downregulation of binding immunoglobulin protein (Bip) promoted IR-mediated endoplasmic reticulum stress to generate DAMPs molecules by PERK and IRE1-α phosphorylation, and increased dendritic cells mature and effector T lymphocytes activation. GSCs treated with Bip knockdown and IR efficiently prevented tumor generation, and reduced post-radiotherapy tumor recurrence. These data suggest that Bip plays a critical role in inhibition of IR-induced ICD in GSCs, and Bip inhibition may be a promising strategy on adjuvant therapy by ameliorating tumor immune microenvironment.
A novel epigenetic regulation of circFoxp1 on Foxp1 in colon cancer cells
Authors: Luo Yanwei , Liu Fengxia , Ma Jinqi , Fu Yunfeng , Gui Rong 
Published: September 2020

AbstractFoxp1 is a tumor suppressor in colon cancer. However, circFoxp1 derived from Foxp1 is an oncogene. In this study, we aim to investigate the role of circFoxp1 in colon cancer and the regulatory mechanism between circFoxp1 and Foxp1. 78 human colon tumor tissues and the matched paracancerous tissues were collected. Quantitative polymerase chain reaction, immunohistochemistry, quantitative methylation-specific PCR, chromatin immunoprecipitation assay, CCK-8 assay, and Tumor xenograft in nude mice were performed. The expression of circFoxp1 was increased and Foxp1 was reduced in colon cancer tissues, which were associated with a poor overall survival rate of the patients with colon cancer. CircFoxp1 recruited DNMT1 to the promoter of Foxp1, leading to promotor hypermethylation, thereby inhibiting Foxp1 transcription. Interfering circFoxp1 by siRNA in SW620 cells significantly inhibited cell viability, while knockdown Foxp1 expression partially restored SW620 cell viability. In addition, knockdown of circFoxp1 significantly sensitized colon cancer cells to Capecitabine in vitro and vivo through regulating Foxp1. We discovered a novel epigenetic pathway that circFoxp1 regulated Foxp1 in colon cancer cells. CircFoxp1 may regulate DNA methylation and demethylation to coordinate colon cancer cell proliferation and participate in chemotherapy drug responses. Therefore, circFoxp1 may be a potential therapeutic target for colon cancer.
Transferring structural knowledge across cognitive maps in humans and models
Authors: Mark Shirley , Moran Rani , Parr Thomas , Kennerley Steve W. , Behrens Timothy E. J. 
Published: September 2020

AbstractRelations between task elements often follow hidden underlying structural forms such as periodicities or hierarchies, whose inferences fosters performance. However, transferring structural knowledge to novel environments requires flexible representations that are generalizable over particularities of the current environment, such as its stimuli and size. We suggest that humans represent structural forms as abstract basis sets and that in novel tasks, the structural form is inferred and the relevant basis set is transferred. Using a computational model, we show that such representation allows inference of the underlying structural form, important task states, effective behavioural policies and the existence of unobserved state-trajectories. In two experiments, participants learned three abstract graphs during two successive days. We tested how structural knowledge acquired on Day-1 affected Day-2 performance. In line with our model, participants who had a correct structural prior were able to infer the existence of unobserved state-trajectories and appropriate behavioural policies.
Summer warming explains widespread but not uniform greening in the Arctic tundra biome
Authors: Berner Logan T. , Massey Richard , Jantz Patrick , Forbes Bruce C. , Macias-Fauria Marc , Myers-Smith Isla , Kumpula Timo , Gauthier Gilles , Andreu-Hayles Laia , Gaglioti Benjamin V. , Burns Patrick , Zetterberg Pentti , D’Arrigo Rosanne , Goetz Scott J. 
Published: September 2020

AbstractArctic warming can influence tundra ecosystem function with consequences for climate feedbacks, wildlife and human communities. Yet ecological change across the Arctic tundra biome remains poorly quantified due to field measurement limitations and reliance on coarse-resolution satellite data. Here, we assess decadal changes in Arctic tundra greenness using time series from the 30 m resolution Landsat satellites. From 1985 to 2016 tundra greenness increased (greening) at ~37.3% of sampling sites and decreased (browning) at ~4.7% of sampling sites. Greening occurred most often at warm sampling sites with increased summer air temperature, soil temperature, and soil moisture, while browning occurred most often at cold sampling sites that cooled and dried. Tundra greenness was positively correlated with graminoid, shrub, and ecosystem productivity measured at field sites. Our results support the hypothesis that summer warming stimulated plant productivity across much, but not all, of the Arctic tundra biome during recent decades.
Indian Ocean warming as a driver of the North Atlantic warming hole
Authors: Hu Shineng , Fedorov Alexey V. 
Published: September 2020

AbstractOver the past century, the subpolar North Atlantic experienced slight cooling or suppressed warming, relative to the background positive temperature trends, often dubbed the North Atlantic warming hole (NAWH). The causes of the NAWH remain under debate. Here we conduct coupled ocean-atmosphere simulations to demonstrate that enhanced Indian Ocean warming, another salient feature of global warming, could increase local rainfall and through teleconnections strengthen surface westerly winds south of Greenland, cooling the subpolar North Atlantic. In decades to follow however, this cooling effect would gradually vanish as the Indian Ocean warming acts to strengthen the Atlantic meridional overturning circulation (AMOC). We argue that the historical NAWH can potentially be explained by such atmospheric mechanisms reliant on surface wind changes, while oceanic mechanisms related to AMOC changes become more important on longer timescales. Thus, explaining the North Atlantic temperature trends and particularly the NAWH requires considering both atmospheric and oceanic mechanisms.
VAV2 signaling promotes regenerative proliferation in both cutaneous and head and neck squamous cell carcinoma
Authors: Lorenzo-Martín L. Francisco , Fernández-Parejo Natalia , Menacho-Márquez Mauricio , Rodríguez-Fdez Sonia , Robles-Valero Javier , Zumalave Sonia , Fabbiano Salvatore , Pascual Gloria , García-Pedrero Juana M. , Abad Antonio , García-Macías María C. , González Nazareno , Lorenzano-Menna Pablo , Pavón Miguel A. , González-Sarmiento Rogelio , Segrelles Carmen , Paramio Jesús M. , Tubío José M. C. , Rodrigo Juan P. , Benitah Salvador A. , Cuadrado Myriam , Bustelo Xosé R. 
Published: September 2020

AbstractRegenerative proliferation capacity and poor differentiation are histological features usually linked to poor prognosis in head and neck squamous cell carcinoma (hnSCC). However, the pathways that regulate them remain ill-characterized. Here, we show that those traits can be triggered by the RHO GTPase activator VAV2 in keratinocytes present in the skin and oral mucosa. VAV2 is also required to maintain those traits in hnSCC patient-derived cells. This function, which is both catalysis- and RHO GTPase-dependent, is mediated by c-Myc- and YAP/TAZ-dependent transcriptomal programs associated with regenerative proliferation and cell undifferentiation, respectively. High levels of VAV2 transcripts and VAV2-regulated gene signatures are both associated with poor hnSCC patient prognosis. These results unveil a druggable pathway linked to the malignancy of specific SCC subtypes.
A diploid assembly-based benchmark for variants in the major histocompatibility complex
Authors: Chin Chen-Shan , Wagner Justin , Zeng Qiandong , Garrison Erik , Garg Shilpa , Fungtammasan Arkarachai , Rautiainen Mikko , Aganezov Sergey , Kirsche Melanie , Zarate Samantha , Schatz Michael C. , Xiao Chunlin , Rowell William J. , Markello Charles , Farek Jesse , Sedlazeck Fritz J. , Bansal Vikas , Yoo Byunggil , Miller Neil , Zhou Xin , Carroll Andrew , Barrio Alvaro Martinez , Salit Marc , Marschall Tobias , Dilthey Alexander T. , Zook Justin M. 
Published: September 2020

AbstractMost human genomes are characterized by aligning individual reads to the reference genome, but accurate long reads and linked reads now enable us to construct accurate, phased de novo assemblies. We focus on a medically important, highly variable, 5 million base-pair (bp) region where diploid assembly is particularly useful - the Major Histocompatibility Complex (MHC). Here, we develop a human genome benchmark derived from a diploid assembly for the openly-consented Genome in a Bottle sample HG002. We assemble a single contig for each haplotype, align them to the reference, call phased small and structural variants, and define a small variant benchmark for the MHC, covering 94% of the MHC and 22368 variants smaller than 50 bp, 49% more variants than a mapping-based benchmark. This benchmark reliably identifies errors in mapping-based callsets, and enables performance assessment in regions with much denser, complex variation than regions covered by previous benchmarks.
Observation of the polaronic character of excitons in a two-dimensional semiconducting magnet CrI3
Authors: Jin Wencan , Kim Hyun Ho , Ye Zhipeng , Ye Gaihua , Rojas Laura , Luo Xiangpeng , Yang Bowen , Yin Fangzhou , Horng Jason Shih An , Tian Shangjie , Fu Yang , Xu Gongjun , Deng Hui , Lei Hechang , Tsen Adam W. , Sun Kai , He Rui , Zhao Liuyan 
Published: September 2020

AbstractExciton dynamics can be strongly affected by lattice vibrations through electron-phonon coupling. This is rarely explored in two-dimensional magnetic semiconductors. Focusing on bilayer CrI3, we first show the presence of strong electron-phonon coupling through temperature-dependent photoluminescence and absorption spectroscopy. We then report the observation of periodic broad modes up to the 8th order in Raman spectra, attributed to the polaronic character of excitons. We establish that this polaronic character is dominated by the coupling between the charge-transfer exciton at 1.96 eV and a longitudinal optical phonon at 120.6 cm−1. We further show that the emergence of long-range magnetic order enhances the electron-phonon coupling strength by ~50% and that the transition from layered antiferromagnetic to ferromagnetic order tunes the spectral intensity of the periodic broad modes, suggesting a strong coupling among the lattice, charge and spin in two-dimensional CrI3. Our study opens opportunities for tailoring light-matter interactions in two-dimensional magnetic semiconductors.
Assessing magnetic and inductive thermal properties of various surfactants functionalised Fe3O4 nanoparticles for hyperthermia
Authors: Rajan Arunima , Sharma Madhulika , Sahu Niroj Kumar 
Published: September 2020

AbstractThis work reports the fabrication of magnetite (Fe3O4) nanoparticles (NPs) coated with various biocompatible surfactants such as glutamic acid (GA), citric acid (CA), polyethylene glycol (PEG), polyvinylpyrrolidine (PVP), ethylene diamine (EDA) and cetyl-trimethyl ammonium bromide (CTAB) via co-precipitation method and their comparative inductive heating ability for hyperthermia (HT) applications. X-ray and electron diffraction analyses validated the formation of well crystallined inverse spinel structured Fe3O4 NPs (crystallite size of ~ 8–10 nm). Magnetic studies confirmed the superparamagnetic (SPM) behaviour for all the NPs with substantial magnetisation (63–68 emu/g) and enhanced magnetic susceptibility is attributed to the greater number of occupations of Fe2+ ions in the lattice as revealed by X-ray photoelectron spectroscopy (XPS). Moreover, distinctive heating response (specific absorption rate, SAR from 130 to 44 W/g) of NPs with similar size and magnetisation is observed. The present study was successful in establishing a direct correlation between relaxation time (~ 9.42–15.92 ns) and heating efficiency of each surface functionalised NPs. Moreover, heat dissipated in different surface grafted NPs is found to be dependent on magnetic susceptibility, magnetic anisotropy and magnetic relaxation time. These results open very promising avenues to design surface functionalised magnetite NPs for effective HT applications.
Dorsolateral prefrontal cortex-based control with an implanted brain–computer interface
Authors: Leinders Sacha , Vansteensel Mariska J. , Branco Mariana P. , Freudenburg Zac V. , Pels Elmar G. M. , Van der Vijgh Benny , Van Zandvoort Martine J. E. , Ramsey Nicolas F. , Aarnoutse Erik J. 
Published: September 2020

AbstractThe objective of this study was to test the feasibility of using the dorsolateral prefrontal cortex as a signal source for brain–computer interface control in people with severe motor impairment. We implanted two individuals with locked-in syndrome with a chronic brain–computer interface designed to restore independent communication. The implanted system (Utrecht NeuroProsthesis) included electrode strips placed subdurally over the dorsolateral prefrontal cortex. In both participants, counting backwards activated the dorsolateral prefrontal cortex consistently over the course of 47 and 22 months, respectively. Moreover, both participants were able to use this signal to control a cursor in one dimension, with average accuracy scores of 78 ± 9% (standard deviation) and 71 ± 11% (chance level: 50%), respectively. Brain–computer interface control based on dorsolateral prefrontal cortex activity is feasible in people with locked-in syndrome and may become of relevance for those unable to use sensorimotor signals for control.
Regulation of degenerative spheroids after injury
Authors: Yong Yu , Gamage Kanchana , Cushman Courtny , Spano Anthony , Deppmann Christopher 
Published: September 2020

AbstractNeuronal injury leads to rapid, programmed disintegration of axons distal to the site of lesion. Much like other forms of axon degeneration (e.g. developmental pruning, toxic insult from neurodegenerative disorder), Wallerian degeneration associated with injury is preceded by spheroid formation along axons. The mechanisms by which injury leads to formation of spheroids and whether these spheroids have a functional role in degeneration remain elusive. Here, using neonatal mouse primary sympathetic neurons, we investigate the roles of players previously implicated in the progression of Wallerian degeneration in injury-induced spheroid formation. We find that intra-axonal calcium flux is accompanied by actin-Rho dependent growth of calcium rich axonal spheroids that eventually rupture, releasing material to the extracellular space prior to catastrophic axon degeneration. Importantly, after injury, Sarm1−/− and DR6−/−, but not Wlds (excess NAD+) neurons, are capable of forming spheroids that eventually rupture, releasing their contents to the extracellular space to promote degeneration. Supplementation of exogenous NAD+ or expressing WLDs suppresses Rho-dependent spheroid formation and degeneration in response to injury. Moreover, injured or trophically deprived Sarm1−/− and DR6−/−, but not Wlds neurons, are resistant to degeneration induced by conditioned media collected from wild-type axons after spheroid rupture. Taken together, these findings place Rho-actin and NAD+ upstream of spheroid formation and may suggest that other mediators of degeneration, such as DR6 and SARM1, mediate post-spheroid rupture events that lead to catastrophic axon disassembly.
Body temperature-dependent microRNA expression analysis in rats: rno-miR-374-5p regulates apoptosis in skeletal muscle cells via Mex3B under hypothermia
Authors: Umehara Takahiro , Kagawa Shinichiro , Tomida Aiko , Murase Takehiko , Abe Yuki , Shingu Keita , Ikematsu Kazuya 
Published: September 2020

AbstractForensic diagnosis of fatal hypothermia is considered difficult because there are no specific findings. Accordingly, exploration of novel fatal hypothermia-specific findings is important. To elucidate the molecular mechanism of homeostasis in hypothermia and identify novel molecular markers to inform the diagnosis of fatal hypothermia, we focused on microRNA expression in skeletal muscle, which plays a role in cold-induced thermogenesis in mammals. We generated rat models of mild, moderate, and severe hypothermia, and performed body temperature-dependent microRNA expression analysis of the iliopsoas muscle using microarray and quantitative real-time PCR (qRT-PCR). The results show that rno-miR-374-5p expression was significantly induced only by severe hypothermia. Luciferase reporter assay and qRT-PCR results indicated that Mex3B expression was regulated by rno-miR-374-5p and decreased with decreasing body temperature. Gene ontology analysis indicated the involvement of Mex3B in positive regulation of GTPase activity. siRNA analysis showed that Mex3B directly or indirectly regulated Kras expression in vitro, and significantly changed the expression of apoptosis-related genes and proteins. Collectively, these results indicate that rno-miR-374-5p was activated by a decrease in body temperature, whereby it contributed to cell survival by suppressing Mex3B and activating or inactivating Kras. Thus, rno-miR-374-5p is a potential supporting marker for the diagnosis of fatal hypothermia.
Forensic tracers of exposure to produced water in freshwater mussels: a preliminary assessment of Ba, Sr, and cyclic hydrocarbons
Authors: Piotrowski Paulina K. , Tasker Travis L. , Geeza Thomas J. , McDevitt Bonnie , Gillikin David P. , Warner Nathaniel R. , Dorman Frank L. 
Published: September 2020

AbstractHydraulic fracturing is often criticized due in part to the potential degradation of ground and surface water quality by high-salinity produced water generated during well stimulation and production. This preliminary study evaluated the response of the freshwater mussel, Elliptio complanata, after exposure to produced water. A limited number of adult mussels were grown over an 8-week period in tanks dosed with produced water collected from a hydraulically fractured well. The fatty tissue and carbonate shells were assessed for accumulation of both inorganic and organic pollutants. Ba, Sr, and cyclic hydrocarbons indicated the potential to accumulate in the soft tissue of freshwater mussels following exposure to diluted oil and gas produced water. Exposed mussels showed accumulation of Ba in the soft tissue several hundred times above background water concentrations and increased concentrations of Sr. Cyclic hydrocarbons were detected in dosed mussels and principle component analysis of gas chromatograph time-of-flight mass spectrometer results could be a novel tool to help identify areas where aquatic organisms are impacted by oil and gas produced water, but larger studies with greater replication are necessary to confirm these results.
Prediction of age-related macular degeneration disease using a sequential deep learning approach on longitudinal SD-OCT imaging biomarkers
Authors: Banerjee Imon , de Sisternes Luis , Hallak Joelle A. , Leng Theodore , Osborne Aaron , Rosenfeld Philip J. , Gregori Giovanni , Durbin Mary , Rubin Daniel 
Published: September 2020

AbstractWe propose a hybrid sequential prediction model called “Deep Sequence”, integrating radiomics-engineered imaging features, demographic, and visual factors, with a recursive neural network (RNN) model in the same platform to predict the risk of exudation within a future time-frame in non-exudative AMD eyes. The proposed model provides scores associated with risk of exudation in the short term (within 3 months) and long term (within 21 months), handling challenges related to variability of OCT scan characteristics and the size of the training cohort. We used a retrospective clinical trial dataset that includes 671 AMD fellow eyes with 13,954 observations before any signs of exudation for training and validation in a tenfold cross validation setting. Deep Sequence achieved high performance for the prediction of exudation within 3 months (0.96 ± 0.02 AUCROC) and within 21 months (0.97 ± 0.02 AUCROC) on cross-validation. Training the proposed model on this clinical trial dataset and testing it on an external real-world clinical dataset showed high performance for the prediction within 3-months (0.82 AUCROC) but a clear decrease in performance for the prediction within 21-months (0.68 AUCROC). While performance differences at longer time intervals may be derived from dataset differences, we believe that the high performance and generalizability achieved in short-term predictions may have a high clinical impact allowing for optimal patient follow-up, adding the possibility of more frequent, detailed screening and tailored treatments for those patients with imminent risk of exudation.