bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of FGF19/FGFR4 signaling inhibition in antitumor activity of multi-kinase inhibitors in hepatocellular carcinoma
Authors: Kanzaki Hiroaki , Chiba Tetsuhiro , Ao Junjie , Koroki Keisuke , Kanayama Kengo , Maruta Susumu , Maeda Takahiro , Kusakabe Yuko , Kobayashi Kazufumi , Kanogawa Naoya , Kiyono Soichiro , Nakamura Masato , Kondo Takayuki , Saito Tomoko , Nakagawa Ryo , Ogasawara Sadahisa , Suzuki Eiichiro , Ooka Yoshihiko , Muroyama Ryosuke , Nakamoto Shingo , Yasui Shin , Tawada Akinobu , Arai Makoto , Kanda Tatsuo , Maruyama Hitoshi , Mimura Naoya , Kato Jun , Zen Yoh , Ohtsuka Masayuki , Iwama Atsushi , Kato Naoya 
Published: March 2021

AbstractFGF19/FGFR4 autocrine signaling is one of the main targets for multi-kinase inhibitors (MKIs). However, the molecular mechanisms underlying FGF19/FGFR4 signaling in the antitumor effects to MKIs in hepatocellular carcinoma (HCC) remain unclear. In this study, the impact of FGFR4/ERK signaling inhibition on HCC following MKI treatment was analyzed in vitro and in vivo assays. Serum FGF19 in HCC patients treated using MKIs, such as sorafenib (n = 173) and lenvatinib (n = 40), was measured by enzyme-linked immunosorbent assay. Lenvatinib strongly inhibited the phosphorylation of FRS2 and ERK, the downstream signaling molecules of FGFR4, compared with sorafenib and regorafenib. Additional use of a selective FGFR4 inhibitor with sorafenib further suppressed FGFR4/ERK signaling and synergistically inhibited HCC cell growth in culture and xenograft subcutaneous tumors. Although serum FGF19high (n = 68) patients treated using sorafenib exhibited a significantly shorter progression-free survival and overall survival than FGF19low (n = 105) patients, there were no significant differences between FGF19high (n = 21) and FGF19low (n = 19) patients treated using lenvatinib. In conclusion, robust inhibition of FGF19/FGFR4 is of importance for the exertion of antitumor effects of MKIs. Serum FGF19 levels may function as a predictive marker for drug response and survival in HCC patients treated using sorafenib.
Concurrent visual working memory bias in sequential integration of approximate number
Authors: Kang Zhiqi , Spitzer Bernhard 
Published: March 2021

AbstractPrevious work has shown bidirectional crosstalk between Working Memory (WM) and perception such that the contents of WM can alter concurrent percepts and vice versa. Here, we examine WM-perception interactions in a new task setting. Participants judged the proportion of colored dots in a stream of visual displays while concurrently holding location- and color information in memory. Spatiotemporally resolved psychometrics disclosed a modulation of perceptual sensitivity consistent with a bias of visual spatial attention towards the memorized location. However, this effect was short-lived, suggesting that the visuospatial WM information was rapidly deprioritized during processing of new perceptual information. Independently, we observed robust bidirectional biases of categorical color judgments, in that perceptual decisions and mnemonic reports were attracted to each other. These biases occurred without reductions in overall perceptual sensitivity compared to control conditions without a concurrent WM load. The results conceptually replicate and extend previous findings in visual search and suggest that crosstalk between WM and perception can arise at multiple levels, from sensory-perceptual to decisional processing.
RNA-seq and GSEA identifies suppression of ligand-gated chloride efflux channels as the major gene pathway contributing to form deprivation myopia
Authors: Vocale Loretta Giummarra , Crewther Sheila , Riddell Nina , Hall Nathan E. , Murphy Melanie , Crewther David 
Published: March 2021

AbstractCurrently there is no consensus regarding the aetiology of the excessive ocular volume that characterizes high myopia. Thus, we aimed to test whether the gene pathways identified by gene set enrichment analysis of RNA-seq transcriptomics refutes the predictions of the Retinal Ion Driven Efflux (RIDE) hypothesis when applied to the induction of form-deprivation myopia (FDM) and subsequent recovery (post-occluder removal). We found that the induction of profound FDM led to significant suppression in the ligand-gated chloride ion channel transport pathway via suppression of glycine, GABAA and GABAC ionotropic receptors. Post-occluder removal for short term recovery from FDM of 6 h and 24 h, induced significant upregulation of the gene families linked to cone receptor phototransduction, mitochondrial energy, and complement pathways. These findings support a model of form deprivation myopia as a Cl− ion driven adaptive fluid response to the modulation of the visual signal cascade by form deprivation that in turn affects the resultant ionic environment of the outer and inner retinal tissues, axial and vitreal elongation as predicted by the RIDE model. Occluder removal and return to normal light conditions led to return to more normal upregulation of phototransduction, slowed growth rate, refractive recovery and apparent return towards physiological homeostasis.
A centrifugal microfluidic cross-flow filtration platform to separate serum from whole blood for the detection of amphiphilic biomarkers
Authors: Lenz Kiersten D. , Jakhar Shailja , Chen Jing W. , Anderson Aaron S. , Purcell Dylan C. , Ishak Mohammad O. , Harris Jennifer F. , Akhadov Leyla E. , Kubicek-Sutherland Jessica Z. , Nath Pulak , Mukundan Harshini 
Published: March 2021

AbstractThe separation of biomarkers from blood is straightforward in most molecular biology laboratories. However, separation in resource-limited settings, allowing for the successful removal of biomarkers for diagnostic applications, is not always possible. The situation is further complicated by the need to separate hydrophobic signatures such as lipids from blood. Herein, we present a microfluidic device capable of centrifugal separation of serum from blood at the point of need with a system that is compatible with biomarkers that are both hydrophilic and hydrophobic. The cross-flow filtration device separates serum from blood as efficiently as traditional methods and retains amphiphilic biomarkers in serum for detection.
Decreasing concentrations of carbonaceous aerosols in China from 2003 to 2013
Authors: Cheng Yan , Chow Judith C. , Watson John G. , Zhou Jiamao , Liu Suixin , Cao Junji 
Published: March 2021

AbstractCarbonaceous aerosols were characterized in 19 Chinese cities during winter and summer of 2013. Measurements of organic carbon (OC) and elemental carbon (EC) levels were compared with those from 14 corresponding cities sampled in 2003 to evaluate effects of emission changes over a decade. Average winter and summer OC and EC decreased by 32% and 17%, respectively, from 2003 to 2013, corresponding to nationwide emission control policies implemented since 2006. The extent of carbon reduction varied by season and by location. Larger reductions were found for secondary organic carbon (SOC, 49%) than primary organic carbon (POC, 25%). PM2.5 mass and total carbon concentrations were three to four times higher during winter than summer especially in the northern cities that use coal combustion for heating.
Metabolic consequences of obesity on the hypercoagulable state of polycystic ovary syndrome
Authors: Moin Abu Saleh Md , Sathyapalan Thozhukat , Diboun Ilhame , Elrayess Mohamed A. , Butler Alexandra E. , Atkin Stephen L. 
Published: March 2021

AbstractPolycystic ovary syndrome (PCOS) women have a hypercoagulable state; however, whether this is intrinsically due to PCOS or, alternatively, a consequence of its metabolic complications is unclear. We determined plasma coagulation pathway protein levels in PCOS (n = 146) and control (n = 97) women recruited to a PCOS biobank. Circulating levels of a panel of 18 clotting pathway proteins were determined by Slow Off-rate Modified Aptamer-scan plasma protein measurement. Cohorts were age matched, though PCOS had elevated body mass index (p < 0.001), insulin (p < 0.001) and C-reactive protein (CRP) (p < 0.0001). Eight pro-coagulation proteins were elevated in PCOS: plasminogen activator inhibitor-1 (p < 0.0001), fibrinogen (p < 0.01), fibrinogen gamma chain (p < 0.0001), fibronectin (p < 0.01), von Willebrand factor (p < 0.05), D-dimer (p < 0.0001), P-selectin (p < 0.05), and plasma kallikrein (p < 0.001). However, two anticoagulant proteins, vitamin K-dependent protein-S (p < 0.0001) and heparin cofactor-II (p < 0.001) were elevated and prothrombin was decreased (p < 0.05). CRP, as a marker of inflammation, and insulin resistance (HOMA-IR) correlated with 11 and 6 of the clotting proteins, respectively (p < 0.05). When matched for BMI < 25 (16 PCOS, 53 controls) HOMA-IR remained elevated (p < 0.05) and heparin cofactor-II was increased (p < 0.05). In a multivariate analysis accounting for inflammation, insulin resistance and BMI, there was no correlation of PCOS with any of the coagulation proteins. The hypercoagulable state in PCOS is not intrinsic to the disease as it can be fully accounted for by BMI, inflammation and insulin resistance.
Structural characterization and duplication modes of pseudogenes in plants
Authors: Mascagni Flavia , Usai Gabriele , Cavallini Andrea , Porceddu Andrea 
Published: March 2021

AbstractWe identified and characterized the pseudogene complements of five plant species: four dicots (Arabidopsis thaliana, Vitis vinifera, Populus trichocarpa and Phaseolus vulgaris) and one monocot (Oryza sativa). Retroposition was considered of modest importance for pseudogene formation in all investigated species except V. vinifera, which showed an unusually high number of retro-pseudogenes in non coding genic regions. By using a pipeline for the classification of sequence duplicates in plant genomes, we compared the relative importance of whole genome, tandem, proximal, transposed and dispersed duplication modes in the pseudo and functional gene complements. Pseudogenes showed higher tendencies than functional genes to genomic dispersion. Dispersed pseudogenes were prevalently fragmented and showed high sequence divergence at flanking regions. On the contrary, those deriving from whole genome duplication were proportionally less than expected based on observations on functional loci and showed higher levels of flanking sequence conservation than dispersed pseudogenes. Pseudogenes deriving from tandem and proximal duplications were in excess compared to functional loci, probably reflecting the high evolutionary rate associated with these duplication modes in plant genomes. These data are compatible with high rates of sequence turnover at neutral sites and double strand break repairs mediated duplication mechanisms.
Individualized prediction of COVID-19 adverse outcomes with MLHO
Authors: Estiri Hossein , Strasser Zachary H. , Murphy Shawn N. 
Published: March 2021

AbstractThe COVID-19 pandemic has devastated the world with health and economic wreckage. Precise estimates of adverse outcomes from COVID-19 could have led to better allocation of healthcare resources and more efficient targeted preventive measures, including insight into prioritizing how to best distribute a vaccination. We developed MLHO (pronounced as melo), an end-to-end Machine Learning framework that leverages iterative feature and algorithm selection to predict Health Outcomes. MLHO implements iterative sequential representation mining, and feature and model selection, for predicting patient-level risk of hospitalization, ICU admission, need for mechanical ventilation, and death. It bases this prediction on data from patients’ past medical records (before their COVID-19 infection). MLHO’s architecture enables a parallel and outcome-oriented model calibration, in which different statistical learning algorithms and vectors of features are simultaneously tested to improve prediction of health outcomes. Using clinical and demographic data from a large cohort of over 13,000 COVID-19-positive patients, we modeled the four adverse outcomes utilizing about 600 features representing patients’ pre-COVID health records and demographics. The mean AUC ROC for mortality prediction was 0.91, while the prediction performance ranged between 0.80 and 0.81 for the ICU, hospitalization, and ventilation. We broadly describe the clusters of features that were utilized in modeling and their relative influence for predicting each outcome. Our results demonstrated that while demographic variables (namely age) are important predictors of adverse outcomes after a COVID-19 infection, the incorporation of the past clinical records are vital for a reliable prediction model. As the COVID-19 pandemic unfolds around the world, adaptable and interpretable machine learning frameworks (like MLHO) are crucial to improve our readiness for confronting the potential future waves of COVID-19, as well as other novel infectious diseases that may emerge.
An ecological niche shift for Neanderthal populations in Western Europe 70,000 years ago
Authors: Banks William E. , Moncel Marie-Hélène , Raynal Jean-Paul , Cobos Marlon E. , Romero-Alvarez Daniel , Woillez Marie-Noëlle , Faivre Jean-Philippe , Gravina Brad , d’Errico Francesco , Locht Jean-Luc , Santos Frédéric 
Published: March 2021

AbstractMiddle Paleolithic Neanderthal populations occupied Eurasia for at least 250,000 years prior to the arrival of anatomically modern humans. While a considerable body of archaeological research has focused on Neanderthal material culture and subsistence strategies, little attention has been paid to the relationship between regionally specific cultural trajectories and their associated existing fundamental ecological niches, nor to how the latter varied across periods of climatic variability. We examine the Middle Paleolithic archaeological record of a naturally constrained region of Western Europe between 82,000 and 60,000 years ago using ecological niche modeling methods. Evaluations of ecological niche estimations, in both geographic and environmental dimensions, indicate that 70,000 years ago the range of suitable habitats exploited by these Neanderthal populations contracted and shifted. These ecological niche dynamics are the result of groups continuing to occupy habitual territories that were characterized by new environmental conditions during Marine Isotope Stage 4. The development of original cultural adaptations permitted this territorial stability.
Acute toxicity assessment of polyaniline/Ag nanoparticles/graphene oxide quantum dots on Cypridopsis vidua and Artemia salina
Authors: Shokry Azza , Khalil Marwa , Ibrahim Hesham , Soliman Moataz , Ebrahim Shaker 
Published: March 2021

AbstractNanotoxicology is argued and considered one of the emerging topics. In this study, polyaniline (PANI)/2-acrylamido-2-methylpropanesulfonic acid (AMPSA) capped silver nanoparticles (NPs)/graphene oxide (GO) quantum dots (QDs) nanocomposite (PANI/Ag (AMPSA)/GO QDs NC) as a nanoadsorbent has a potential for removal of toxic hexavalent chromium (Cr(VI)) ions from water. The acute toxicity of this NC was evaluated on Artemia salina and freshwater Ostracods (Cypridopsis vidua) larvae for 48 h. The measurements were made at 24 and 48 h with 3 repetitions. The 50% effective concentration (EC50) values of the NC were determined after the exposure of these organisms. According to the results of the optical microscope, it was found that both experimental organisms intake the NC. In the toxicity results of Ostracods, the NC had a highly toxic effect only at 250 mg/L after 48 h and the EC50 value was 157.6 ± 6.4 mg/L. For Artemia salina individuals, it was noted that they were less sensitive than the Ostracods and EC50 value was 476 ± 25.1 mg/L after 48 h. These results indicated that PANI/Ag (AMPSA)/GO QDs NC has low toxicity towards both investigated organisms.
Warming temperatures lead to reduced summer carbon sequestration in the U.S. Corn Belt
Authors: Yu Zhongjie , Griffis Timothy J. , Baker John M. 
Published: March 2021

AbstractThe response of highly productive croplands at northern mid-latitudes to climate change is a primary source of uncertainty in the global carbon cycle, and a concern for future food production. We present a decadal time series (2007 to 2019) of hourly CO2 concentration measured at a very tall tower in the United States Corn Belt. Analyses of this record, with other long-term data in the region, reveal that warming has had a positive impact on net CO2 uptake during the early crop growth stage, but has reduced net CO2 uptake in both croplands and natural ecosystems during the peak growing season. Future increase in summer temperature is projected to reduce annual CO2 sequestration in the Corn Belt by 10–20%. These findings highlight the dynamic control of warming on cropland CO2 exchange and crop yields and challenge the paradigm that warming will continue to favor CO2 sequestration in northern mid-latitude ecosystems.
iTRAQ-based comparative proteomic analysis in different developmental stages ofEchinococcus granulosus
Authors: Li Xin , Jiang Song , Wang Xuhai , Hui Wenqiao , Jia Bin 
Published: March 2021

Cystic echinococcosis, caused by infection with the larval stage of the cestodeEchinococcus granulosus, is a chronic zoonosis. The lifecycle of theE. granulosusparasite includes three consecutive stages that require specific gene regulation or protein expression to survive environmental shifts between definitive hosts and intermediate hosts. The aim of the present study is to screen and analyze the stage differential antigens to be considered for vaccine development againstE. granulosus. By using the iTRAQ (isobaric tags for relative and absolute quantification) method, the differentially expressed proteins were selected from the three consecutive developmental stages ofE. granulosus: oncosphere, adult tapeworms, and protoscolex. Through a bioinformatics analysis including Clusters of Orthologous Groups (COG), Gene Ontology (GO), and pathway metabolic annotation, we identified some proteins of interest from each stage. The results showed that a large number of differentially expressed proteins (375: oncosphere vs. adult, 346: oncosphere vs. protoscolex, and 391: adult vs. protoscolex) were identified from the three main lifecycle stages. Analysis of the differential protein pathways showed that these differential proteins are mainly enriched in metabolic pathways, Huntington’s diseases, Alzheimer’s diseases, and ribosome metabolic pathways. Interestingly, among these differential proteins, expression levels of paramyosin, HSP60, HSP70, HSP90, cathepsin L1, cathepsin D, casein kinase, and calmodulin were significantly higher in the oncosphere than in the adult or protoscolex (p < 0.05). We hope our findings will help to identify potential targets for diagnosis or for therapeutic and prophylactic intervention.
Emerging infrastructures: the politics of radium and the validation of radiotherapy in India’s first tertiary cancer hospital
Authors: Smith Robert D. 
Published: March 2021

AbstractThis article traces the history of India’s first tertiary cancer hospital, Tata Memorial Hospital (TMH). TMH was originally conceived in 1932 as a philanthropic project by the Tatas, an elite Parsi business family in Bombay. The founding of TMH represented a form of philanthro-capitalism which both enabled the Tatas to foster a communal acceptance for big businesses in Bombay and provide the Tatas with the opportunity to place stakes in the emerging nuclear research economy seen as essential to the scientific nationalist sentiment of the post-colonial state. In doing this, the everyday activities of TMH placed a heavy emphasis on nuclear research. In a time when radium for the treatment of cancer was still seen as ‘quackery’ in much of the world, the philanthro-capitalist investment and the interest in nuclear research by the post-colonial state provided an environment where radium medicine was able to be validated. The validation of radiotherapy at TMH influenced how other cancer hospitals in India developed and also provided significant resources for cancer research in early-mid twentieth century India. Ultimately, this article identifies ways in which cancer comes to be seen as relevant in the global south and raises questions on the relationship between local and global actors in setting health priorities.
Characterization and simulation of 280 nm UV-LED degradation
Authors: Su Mengwei , Zhu Xinglin , Guo Qi , Chen Zhiqiang , Deng Shaodong , Chen Ziqian , Wang Yukun , Deng Jianyu , Sun Wenhong 
Published: March 2021

In this paper, we investigated the degradation of 280 nm ultraviolet light emitting diodes (UV-LEDs) using both optical and electrical characterization methods. By capacitance–voltage methods, we were able to reveal that carriers in the quantum wells closer to the sapphire substrate would redistribute with aging time and stress currents. We compared these distributions with simulations and found that both the polarization charges at the AlGaN/AlGaN heterostructure interface and the quantum well doping were significantly affected by the stress. These results indicated that the migration and diffusion of donor impurities/dislocations under the current flow could lead to the deterioration of the quantum well crystal quality and contribute to the attenuation of optical power. Our study suggests a novel mechanism for degradation of UV-LEDs, and the developed techniques provide a new approach for future reliability analysis.
How the growth of ice depends on the fluid dynamics underneath
Authors: Wang Ziqi , Calzavarini Enrico , Sun Chao , Toschi Federico 
Published: March 2021

SignificanceLandscapes, resulting from ice–water interactions coupled with solidification/melting, are ubiquitous in nature, yet most previous studies have not considered the rich fluid dynamics induced by water density anomaly underneath the moving ice front, which can drastically change system behaviors. By experiments, numerical simulations, and theoretical modeling, we investigate water solidification and its dynamical coupling with (turbulent) convective flows. We reveal four distinct regimes and develop a theoretical model capable of accurately capturing ice thickness and icing timescales. Physical mechanisms revealed from this study, when applied to geological recordings of lake ice, can provide an indicator of climate change. The current investigations offer deeper insight into understanding the coupling between phase change and stratification in marine, geophysical, and astrophysical systems.
A multiplier peroxiporin signal transduction pathway powers piscine spermatozoa
Authors: Chauvigné François , Ducat Carla , Ferré Alba , Hansen Tom , Carrascal Montserrat , Abián Joaquín , Finn Roderick Nigel , Cerdà Joan 
Published: March 2021

SignificanceSpermatozoon swimming performance is critical for fertilization success in fishes, yet the cellular mechanisms that regulate this vital trait are poorly understood. Here, we discovered that a water channel protein, acting as an H2O2channel (peroxiporin) to detoxify the mitochondria, directly regulates the velocity and progressive motility of both freshwater and marine spermatozoa. The mitochondrial insertion of the peroxiporin is controlled by an increasingly sophisticated hierarchy of intracellular signaling cascades, which evolved into a multiplier stress-activated pathway in modern marine species. These adaptive solutions maximize the postactivated swimming performance of sperm under conditions of high osmotic and oxidative stress. Our findings thus reveal that the pathways regulating the peroxiporin transport in fish spermatozoa provide an advantage for competitive fertilization success.