bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell analysis reveals the intra-tumor heterogeneity and identifies MLXIPL as a biomarker in the cellular trajectory of hepatocellular carcinoma
Authors: Dong Xiao , Wang Fan , Liu Chuan , Ling Jing , Jia Xuebing , Shen Feifei , Yang Ning , Zhu Sibo , Zhong Lin , Li Qi 
Published: January 2021

AbstractHepatocellular carcinoma (HCC) is a globally prevailing cancer with a low 5-year survival rate. Little is known about its intricate gene expression profile. Single-cell RNA sequencing is an indispensable tool to explore the genetic characteristics of HCC at a more detailed level. In this study, we profiled the gene expression of single cells from human HCC tumor and para-tumor tissues using the Smart-seq 2 sequencing method. Based on differentially expressed genes, we identified heterogeneous subclones in HCC tissues, including five HCC and two hepatocyte subclones. We then carried out hub-gene co-network and functional annotations analysis followed pseudo-time analysis with regulated transcriptional factor co-networks to determine HCC cellular trajectory. We found that MLX interacting protein like (MLXIPL) was commonly upregulated in the single cells and tissues and associated with a poor survival rate in HCC. Mechanistically, MLXIPL activation is crucial for promoting cell proliferation and inhibits cell apoptosis by accelerating cell glycolysis. Taken together, our work identifies the heterogeneity of HCC subclones, and suggests MLXIPL might be a promising therapeutic target for HCC.
Structure of SRSF1 RRM1 bound to RNA reveals an unexpected bimodal mode of interaction and explains its involvement in SMN1 exon7 splicing
Authors: Cléry Antoine , Krepl Miroslav , Nguyen Cristina K. X. , Moursy Ahmed , Jorjani Hadi , Katsantoni Maria , Okoniewski Michal , Mittal Nitish , Zavolan Mihaela , Sponer Jiri , Allain Frédéric H.-T. 
Published: January 2021

AbstractThe human prototypical SR protein SRSF1 is an oncoprotein that contains two RRMs and plays a pivotal role in RNA metabolism. We determined the structure of the RRM1 bound to RNA and found that the domain binds preferentially to a CN motif (N is for any nucleotide). Based on this solution structure, we engineered a protein containing a single glutamate to asparagine mutation (E87N), which gains the ability to bind to uridines and thereby activates SMN exon7 inclusion, a strategy that is used to cure spinal muscular atrophy. Finally, we revealed that the flexible inter-RRM linker of SRSF1 allows RRM1 to bind RNA on both sides of RRM2 binding site. Besides revealing an unexpected bimodal mode of interaction of SRSF1 with RNA, which will be of interest to design new therapeutic strategies, this study brings a new perspective on the mode of action of SRSF1 in cells.
PKA drives an increase in AMPA receptor unitary conductance during LTP in the hippocampus
Authors: Park Pojeong , Georgiou John , Sanderson Thomas M. , Ko Kwang-Hee , Kang Heather , Kim Ji-il , Bradley Clarrisa A. , Bortolotto Zuner A. , Zhuo Min , Kaang Bong-Kiun , Collingridge Graham L. 
Published: January 2021

AbstractLong-term potentiation (LTP) at hippocampal CA1 synapses can be expressed by an increase either in the number (N) of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors or in their single channel conductance (γ). Here, we have established how these distinct synaptic processes contribute to the expression of LTP in hippocampal slices obtained from young adult rodents. LTP induced by compressed theta burst stimulation (TBS), with a 10 s inter-episode interval, involves purely an increase in N (LTPN). In contrast, either a spaced TBS, with a 10 min inter-episode interval, or a single TBS, delivered when PKA is activated, results in LTP that is associated with a transient increase in γ (LTPγ), caused by the insertion of calcium-permeable (CP)-AMPA receptors. Activation of CaMKII is necessary and sufficient for LTPN whilst PKA is additionally required for LTPγ. Thus, two mechanistically distinct forms of LTP co-exist at these synapses.
Male fertility in Arabidopsis requires active DNA demethylation of genes that control pollen tube function
Authors: Khouider Souraya , Borges Filipe , LeBlanc Chantal , Ungru Alexander , Schnittger Arp , Martienssen Robert , Colot Vincent , Bouyer Daniel 
Published: January 2021

AbstractActive DNA demethylation is required for sexual reproduction in plants but the molecular determinants underlying this epigenetic control are not known. Here, we show in Arabidopsis thaliana that the DNA glycosylases DEMETER (DME) and REPRESSOR OF SILENCING 1 (ROS1) act semi-redundantly in the vegetative cell of pollen to demethylate DNA and ensure proper pollen tube progression. Moreover, we identify six pollen-specific genes with increased DNA methylation as well as reduced expression in dme and dme;ros1. We further show that for four of these genes, reinstalling their expression individually in mutant pollen is sufficient to improve male fertility. Our findings demonstrate an essential role of active DNA demethylation in regulating genes involved in pollen function.
Mathematical model of COVID-19 intervention scenarios for São Paulo—Brazil
Authors: Pinto Neto Osmar , Kennedy Deanna M. , Reis José Clark , Wang Yiyu , Brizzi Ana Carolina Brisola , Zambrano Gustavo José , de Souza Joabe Marcos , Pedroso Wellington , de Mello Pedreiro Rodrigo Cunha , de Matos Brizzi Bruno , Abinader Ellysson Oliveira , Zângaro Renato Amaro 
Published: January 2021

AbstractWith COVID-19 surging across the world, understanding the effectiveness of intervention strategies on transmission dynamics is of primary global health importance. Here, we develop and analyze an epidemiological compartmental model using multi-objective genetic algorithm design optimization to compare scenarios related to strategy type, the extent of social distancing, time window, and personal protection levels on the transmission dynamics of COVID-19 in São Paulo, Brazil. The results indicate that the optimal strategy for São Paulo is to reduce social distancing over time with a stepping-down reduction in the magnitude of social distancing every 80-days. Our results also indicate that the ability to reduce social distancing depends on a 5–10% increase in the current percentage of people strictly following protective guidelines, highlighting the importance of protective behavior in controlling the pandemic. Our framework can be extended to model transmission dynamics for other countries, regions, states, cities, and organizations.
Low-dose decitabine priming endows CAR T cells with enhanced and persistent antitumour potential via epigenetic reprogramming
Authors: Wang Yao , Tong Chuan , Dai Hanren , Wu Zhiqiang , Han Xiao , Guo Yelei , Chen Deyun , Wei Jianshu , Ti Dongdong , Liu Zongzhi , Mei Qian , Li Xiang , Dong Liang , Nie Jing , Zhang Yajing , Han Weidong 
Published: January 2021

AbstractInsufficient eradication capacity and dysfunction are common occurrences in T cells that characterize cancer immunotherapy failure. De novo DNA methylation promotes T cell exhaustion, whereas methylation inhibition enhances T cell rejuvenation in vivo. Decitabine, a DNA methyltransferase inhibitor approved for clinical use, may provide a means of modifying exhaustion-associated DNA methylation programmes. Herein, anti-tumour activities, cytokine production, and proliferation are enhanced in decitabine-treated chimeric antigen receptor T (dCAR T) cells both in vitro and in vivo. Additionally, dCAR T cells can eradicate bulky tumours at a low-dose and establish effective recall responses upon tumour rechallenge. Antigen-expressing tumour cells trigger higher expression levels of memory-, proliferation- and cytokine production-associated genes in dCAR T cells. Tumour-infiltrating dCAR T cells retain a relatively high expression of memory-related genes and low expression of exhaustion-related genes in vivo. In vitro administration of decitabine may represent an option for the generation of CAR T cells with improved anti-tumour properties.
Role of dams in reducing global flood exposure under climate change
Authors: Boulange Julien , Hanasaki Naota , Yamazaki Dai , Pokhrel Yadu 
Published: January 2021

AbstractGlobally, flood risk is projected to increase in the future due to climate change and population growth. Here, we quantify the role of dams in flood mitigation, previously unaccounted for in global flood studies, by simulating the floodplain dynamics and flow regulation by dams. We show that, ignoring flow regulation by dams, the average number of people exposed to flooding below dams amount to 9.1 and 15.3 million per year, by the end of the 21stcentury (holding population constant), for the representative concentration pathway (RCP) 2.6 and 6.0, respectively. Accounting for dams reduces the number of people exposed to floods by 20.6 and 12.9% (for RCP2.6 and RCP6.0, respectively). While environmental problems caused by dams warrant further investigations, our results indicate that consideration of dams significantly affect the estimation of future population exposure to flood, emphasizing the need to integrate them in model-based impact analysis of climate change.
Contact-independent killing mediated by a T6SS effector with intrinsic cell-entry properties
Authors: Song Li , Pan Junfeng , Yang Yantao , Zhang Zhenxing , Cui Rui , Jia Shuangkai , Wang Zhuo , Yang Changxing , Xu Lei , Dong Tao G. , Wang Yao , Shen Xihui 
Published: January 2021

AbstractBacterial type VI secretion systems (T6SSs) inject toxic effectors into adjacent eukaryotic and prokaryotic cells. It is generally thought that this process requires physical contact between the two cells. Here, we provide evidence of contact-independent killing by a T6SS-secreted effector. We show that the pathogen Yersinia pseudotuberculosis uses a T6SS (T6SS-3) to secrete a nuclease effector that kills other bacteria in vitro and facilitates gut colonization in mice. The effector (Tce1) is a small protein that acts as a Ca2+- and Mg2+-dependent DNase, and its toxicity is inhibited by a cognate immunity protein, Tci1. As expected, T6SS-3 mediates canonical, contact-dependent killing by directly injecting Tce1 into adjacent cells. In addition, T6SS-3 also mediates killing of neighboring cells in the absence of cell-to-cell contact, by secreting Tce1 into the extracellular milieu. Efficient contact-independent entry of Tce1 into target cells requires proteins OmpF and BtuB in the outer membrane of target cells. The discovery of a contact-independent, long-range T6SS toxin delivery provides a new perspective for understanding the physiological roles of T6SS in competition. However, the mechanisms mediating contact-independent uptake of Tce1 by target cells remain unclear.
China’s plastic import ban increases prospects of environmental impact mitigation of plastic waste trade flow worldwide
Authors: Wen Zongguo , Xie Yiling , Chen Muhan , Dinga Christian Doh 
Published: January 2021

AbstractSince the late 1990s, the trend of plastic waste shipment from developed to developing countries has been increasing. In 2017, China announced an unprecedented ban on its import of most plastic waste, resulting in a sharp decline in global plastic waste trade flow and changes in the treatment structure of countries, whose impacts on global environmental sustainability are enormous but yet unexamined. Here, through the life cycle assessment (LCA) method, we quantified the environmental impacts of changes in the flow patterns and treatment methods of 6 types of plastic waste in 18 countries subsequent to the ban. In the short term, the ban significantly improved four midpoint indicators of environmental impact, albeit contributed to global warming. An annual saving of about 2.35 billion euros of eco-cost was realized, which is equivalent to 56% of plastic waste global trade value in 2017. To achieve global environmental sustainability in the long run, countries should gradually realize the transition from export to domestic management, and from landfill to recycling, which would realize eco-costs savings of about 1.54–3.20 billion euros.
B-type natriuretic peptide (BNP) predicts 90-day mortality and need for paracentesis in cirrhotic patients without systolic heart failure
Authors: Araujo Tiago , Vohra Ishaan , Palacios Pedro , Katiyar Vatsala , Flores Estefania , Randhawa Tejinder , Wang Yuchen , Abu-Omar Yazan , Mukthinuthalapati Vijaya , Mutneja Hemant , Patel Sanjay A. , Attar Bashar 
Published: January 2021

AbstractFluid overload is a common complication in patients with cirrhosis. B-type natriuretic peptide (BNP) is a marker of increased blood volume, commonly used in heart failure, that has been shown to be elevated in patients with liver disease. This study examined if BNP levels can be used to determine prognosis and predict worsening of ascites in patients with cirrhosis without concomitant heart disease. A retrospective study was performed at a large urban hospital in Chicago, Illinois and included 430 patients with cirrhosis who had BNP levels ordered during their hospital stay. Patients with clinical heart failure, arrhythmias or pulmonary hypertension were excluded. The primary outcome was 90-day mortality and the secondary outcome was a requirement for therapeutic paracentesis in the 90 days following BNP results. 53 patients (12%) had BNP levels ≥ 300 pg/mL. They had significantly increased serum levels of creatinine, bilirubin, and International Normalized Ratio (INR) when compared to those with BNP < 300 pg/mL. Patients with higher BNP had significantly higher mortality rates (HR 3.49; p = 0.037) and were more likely to require therapeutic paracentesis (HR 2.26; p = 0.02) in the next 90 days. A BNP ≥ 300 pg/mL had specificity of 88.2% in predicting 90-day mortality. BNP may serve as a practical and reliable marker of underlying disease severity in patients with cirrhosis, with potential to be included in prognostication tools for assessment of end-stage liver disease.
Craniofacial shape in patients with beta thalassaemia: a geometric morphometric analysis
Authors: Roussos Petros , Mitsea Anastasia , Halazonetis Demetrios , Sifakakis Iosif 
Published: January 2021

AbstractThe shape of the craniofacial complex of patients with beta thalassaemia was evaluated using geometric morphometrics on lateral cephalometric radiographs and was compared with matched controls. The beta thalassaemia group consisted of 40 patients (16 females, 24 males, mean age 33.4). Each patient was matched by age and gender to two controls (32 females, 48 males, mean age 33.1). The 120 lateral cephalometric radiographs were digitized and traced with 15 curves, 10 landmarks and 117 sliding semi-landmarks. These landmarks were subjected to Procrustes superimposition and principal component analysis in order to describe shape variability of the cranial base, maxilla and mandible, as well as of the entire craniofacial complex for each sex. The first 4 principal components accounted for 50% of the total sample’s variability. The beta thalassaemia group was significantly different in overall shape to the control group for both sexes. Similar findings were noted for the maxilla, the mandible and the cranial base. The main differences were related to smaller mandibular body for the thalassaemia group, midface protrusion and decrease in posterior face height. The shape of the craniofacial complex in these patients is prone to be more convex and hyperdivergent.
Circulating tumour cells as an indicator of early and systemic recurrence after surgical resection in pancreatic ductal adenocarcinoma
Authors: Park Yejong , Jun Hye Ryeong , Choi Hwi Wan , Hwang Dae Wook , Lee Jae Hoon , Song Ki Byung , Lee Woohyung , Kwon Jaewoo , Ha Su Hyeon , Jun Eunsung , Kim Song Cheol 
Published: January 2021

AbstractEarly recurrence in pancreatic ductal adenocarcinoma (PDAC) is a decisive factor in determining a patient's prognosis. We determined in our current study whether circulating tumour cells (CTCs) exist in the blood of PDAC patients and can be used as a predictor of recurrence patterns (i.e. time and site) after surgical resection. Between December 2017 and November 2018, the mononuclear cell layer was obtained from the peripheral blood of 36 patients diagnosed with PDAC. CTCs were then isolated using the CD-PRIME™ platform and detected via immunostaining. The patient records were analyzed to correlate these data with survival and recurrence patterns. Twelve patients were CTC-positive (33.3%) and showed a significantly frequent rate of systemic recurrence (distant metastases and peritoneal dissemination) (p = 0.025). On multi-variable logistic regression analysis, CTC positivity was an independent risk factor for early recurrence (p = 0.027) and for systemic recurrence (p = 0.033). In summary, the presence or absence of CTC in the blood of the patients with PDAC could help predict the recurrence pattern after surgery. PDAC patients with CTC positivity at tumour diagnosis should therefore undergo a comprehensive strategy for systemic therapy and active monitoring to detect possible early recurrence.
Predicting mammalian species at risk of being infected by SARS-CoV-2 from an ACE2 perspective
Authors: Wei Yulong , Aris Parisa , Farookhi Heba , Xia Xuhua 
Published: January 2021

AbstractSARS-CoV-2 can transmit efficiently in humans, but it is less clear which other mammals are at risk of being infected. SARS-CoV-2 encodes a Spike (S) protein that binds to human ACE2 receptor to mediate cell entry. A species with a human-like ACE2 receptor could therefore be at risk of being infected by SARS-CoV-2. We compared between 132 mammalian ACE2 genes and between 17 coronavirus S proteins. We showed that while global similarities reflected by whole ACE2 gene alignments are poor predictors of high-risk mammals, local similarities at key S protein-binding sites highlight several high-risk mammals that share good ACE2 homology with human. Bats are likely reservoirs of SARS-CoV-2, but there are other high-risk mammals that share better ACE2 homologies with human. Both SARS-CoV-2 and SARS-CoV are closely related to bat coronavirus. Yet, among host-specific coronaviruses infecting high-risk mammals, key ACE2-binding sites on S proteins share highest similarities between SARS-CoV-2 and Pangolin-CoV and between SARS-CoV and Civet-CoV. These results suggest that direct coronavirus transmission from bat to human is unlikely, and that rapid adaptation of a bat SARS-like coronavirus in different high-risk intermediate hosts could have allowed it to acquire distinct high binding potential between S protein and human-like ACE2 receptors.
Three-dimensional distribution of CT attenuation in the lumbar spine pedicle wall
Authors: Irie Tomoyo Y. , Irie Tohru , Espinoza Orías Alejandro A. , Segami Kazuyuki , Iwasaki Norimasa , An Howard S. , Inoue Nozomu 
Published: January 2021

AbstractThis study investigated in vivo the three-dimensional distribution of CT attenuation in the lumbar spine pedicle wall measured in Hounsfield Unit (HU). Seventy-five volunteers underwent clinical lumbar spine CT scans. Data was analyzed with custom-written software to determine the regional variation in pedicle wall attenuation values. A cylindrical coordinate system oriented along the pedicle’s long axis was used to calculate the pedicular wall attenuation distribution three-dimensionally and the highest attenuation value was identified. The pedicular cross-section was divided into four quadrants: lateral, medial, cranial, and caudal. The mean HU value for each quadrant was calculated for all lumbar spine levels (L1–5). The pedicle wall attenuation was analyzed by gender, age, spinal levels and anatomical quadrant. The mean HU values of the pedicle wall at L1 and L5 were significantly lower than the values between L2–4 in both genders and in both age groups. Furthermore, the medial quadrant showed higher HU values than the lateral quadrant at all levels and the caudal quadrant showed higher HU values at L1–3 and lower HU values at L4–5 than the cranial quadrant. These findings may explain why there is a higher incidence of pedicle screw breach in the pedicle lateral wall.
Separation of copper ions by nanocomposites using adsorption process
Authors: Danesh Nasim , Ghorbani Mohsen , Marjani Azam 
Published: January 2021

AbstractIn this research, a novel nanocomposite adsorbent, graphene oxide modified with magnetite nanoparticles and Lauric acid containing ethylenediaminetetraacetic acid (GFLE) has been applied for the eliminate of Cu2+ ions. Adsorption performance was considered as a function of solution pH, Cu2+ ions concentration (C Cu2+), and temperature (T) and contact time (t). The levels of each variable were statistically optimized by Central Composite Design (CCD) and the response surface methodology (RSM) procedure to enhance the yield of system design. In these calculations, Y was measured as the response (the secondary concentration of Cu2+ ions in mg L−1). Highest copper adsorption occurred at time of 105 min, temperature of 40 °C, the initial concentration of 280 mg L−1, and pH = 1. The sorption equilibrium was well demonstrated using the Freundlich isotherm model. The second-order kinetics model suggested that the sorption mechanism might be ion exchange reactions. Thermodynamic factors and activation energy values displayed that the uptake process of Cu2+ ions was spontaneous, feasible, endothermic and physical in nature. Regeneration studies also revealed that GFLE could be consistently reused up to 3 cycles.
Room air constituent concentrations from use of electronic nicotine delivery systems and cigarettes using different ventilation conditions
Authors: Oldham Michael J. , Sehgal Anil , Cohen Gal , Chen Joey , Evans Blair , Heraldez Daniel 
Published: January 2021

AbstractTo assess potential exposure of non-users to exhaled constituents from pod and cartridge electronic nicotine delivery systems (ENDS) products, an environmental clinical study was conducted with (n = 43) healthy adult smokers. Room air concentrations of 34 selected constituents (nicotine, propylene glycol, glycerin, 15 carbonyls, 12 volatile organic compounds, and 4 trace metals) and particle number concentration (0.3 to 25 µm) were compared from use of two ENDS products and conventional cigarettes using room ventilations representative of a residential, an office or a hospitality setting over a 4-h. exposure period. Products used were JUUL ENDS, Virginia Tobacco flavor (Group I), VUSE Solo, Original flavor (Group II) (5.0 and 4.8% nicotine by weight, respectively) and subjects’ own conventional cigarettes (Group III). Cumulative 4-h room air sampling and particle counting were performed during prescribed (Groups I and II) and ad libitum product use (all Groups). Conventional cigarette use resulted in significantly more constituents detected and higher 4-h cumulative constituent concentrations compared to use of the ENDS products tested, except for the predominant ENDS ingredients, propylene glycol and glycerin. Use of conventional cigarettes also resulted in greater total particle number concentration than either prescribed or ad libitum use of either of the ENDS used in this study.