bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reflections on Changing Times for Pediatric Integrated Primary Care During COVID-19 Pandemic
Authors: Stancin Terry 
Published: September 2020

Objective: The COVID-19 pandemic has had a monumental impact on health care delivery. The pediatric integrated primary care (IPC) program at MetroHealth Medical Center, 1 of the oldest such programs in the United States, has been profoundly changed by the COVID-19 pandemic of 2020. Method: This commentary provides a reflection on the early response of 1 established IPC program to the COVID-19 pandemic. Results: Initial markers of successful adaptation to care delivery and training models include efforts that incorporate virtual consultation and telehealth practices. Conclusions: The impact of the COVID-19 pandemic on pediatric psychology in IPC settings will largely depend on the flexibility and adaptability of workflows and training methods to meet the needs of the changing landscape. Implications for Impact Statement Pediatric integrated primary care (IPC) has been profoundly impacted by the COVID19 pandemic of 2020. The future success of IPC will depend on adapting models and training efforts that incorporate virtual and telehealth formats.
Clinical relevance of blood-based ctDNA analysis: mutation detection and beyond
Authors: Keller Laura , Belloum Yassine , Wikman Harriet , Pantel Klaus 
Published: September 2020

AbstractCell-free DNA (cfDNA) derived from tumours is present in the plasma of cancer patients. The majority of currently available studies on the use of this circulating tumour DNA (ctDNA) deal with the detection of mutations. The analysis of cfDNA is often discussed in the context of the noninvasive detection of mutations that lead to resistance mechanisms and therapeutic and disease monitoring in cancer patients. Indeed, substantial advances have been made in this area, with the development of methods that reach high sensitivity and can interrogate a large number of genes. Interestingly, however, cfDNA can also be used to analyse different features of DNA, such as methylation status, size fragment patterns, transcriptomics and viral load, which open new avenues for the analysis of liquid biopsy samples from cancer patients. This review will focus on the new perspectives and challenges of cfDNA analysis from mutation detection in patients with solid malignancies.
PIK3R3 inhibits cell senescence through p53/p21 signaling
Authors: Chen Qianzhi , Sun Xuling , Luo Xuelai , Wang Jing , Hu Junbo , Feng Yongdong 
Published: September 2020

AbstractCellular senescence is a stress response of human cells that removes potentially harmful cells by initiating cell cycle arrest. Inducing senescence of tumor cells may be an effective tumor-inhibiting strategy. In this study we found that PIK3R3 could inhibit the cell senescence of colorectal cancer cells and promote cell proliferation through the p53/p21 signal pathway. PIK3R3 could bind to p53 and inhibit the binding of p53 to the p21 gene promoter region, and thus affecting the transcriptional activity of p21 gene. Our study has provided new evidence of the role of PIK3R3 in p53 regulation and inhibition of PIK3R3 may be one of the potential targets of tumor therapy.
A genome-wide association study uncovers a critical role of the RsPAP2 gene in red-skinned Raphanus sativus L.
Authors: Fan Lianxue , Wang Yan , Xu Liang , Tang Mingjia , Zhang Xiaoli , Ying Jiali , Li Cui , Dong Junhui , Liu Liwang 
Published: September 2020

AbstractRadish (Raphanus sativus L.) taproot contains high concentrations of flavonoids, including anthocyanins (ATCs), in red-skinned genotypes. However, little information on the genetic regulation of ATC biosynthesis in radish is available. A genome-wide association study of radish red skin color was conducted using whole-genome sequencing data derived from 179 radish genotypes. The R2R3-MYB transcription factor production of anthocyanin pigment 2 (PAP2) gene was found in the region associated with a leading SNP located on chromosome 2. The amino acid sequence encoded by the RsPAP2 gene was different from those of the other published RsMYB genes responsible for the red skin color of radish. The overexpression of the RsPAP2 gene resulted in ATC accumulation in Arabidopsis and radish, which was accompanied by the upregulation of several ATC-related structural genes. RsPAP2 was found to bind the RsUFGT and RsTT8 promoters, as shown by a dual-luciferase reporter system and a yeast one-hybrid assay. The promoter activities of the RsANS, RsCHI, RsPAL, and RsUFGT genes could be strongly activated by coinfiltration with RsPAP2 and RsTT8. These findings showed the effectiveness of GWAS in identifying candidate genes in radish and demonstrated that RsPAP2 could (either directly or together with its cofactor RsTT8) regulate the transcript levels of ATC-related genes to promote ATC biosynthesis, facilitating the genetic enhancement of ATC contents and other related traits in radish.
Anomalous supply shortages from dynamic pricing in on-demand mobility
Authors: Schröder Malte , Storch David-Maximilian , Marszal Philip , Timme Marc 
Published: September 2020

AbstractDynamic pricing schemes are increasingly employed across industries to maintain a self-organized balance of demand and supply. However, throughout complex dynamical systems, unintended collective states exist that may compromise their function. Here we reveal how dynamic pricing may induce demand-supply imbalances instead of preventing them. Combining game theory and time series analysis of dynamic pricing data from on-demand ride-hailing services, we explain this apparent contradiction. We derive a phase diagram demonstrating how and under which conditions dynamic pricing incentivizes collective action of ride-hailing drivers to induce anomalous supply shortages. We identify characteristic patterns in the price dynamics reflecting these supply anomalies by disentangling different timescales in price time series of ride-hailing services at 137 locations across the globe. Our results provide systemic insights for the regulation of dynamic pricing, in particular in publicly accessible mobility systems, by unraveling under which conditions dynamic pricing schemes promote anomalous supply shortages.
Raman-guided subcellular pharmaco-metabolomics for metastatic melanoma cells
Authors: Du Jiajun , Su Yapeng , Qian Chenxi , Yuan Dan , Miao Kun , Lee Dongkwan , Ng Alphonsus H. C. , Wijker Reto S. , Ribas Antoni , Levine Raphael D. , Heath James R. , Wei Lu 
Published: September 2020

AbstractNon-invasively probing metabolites within single live cells is highly desired but challenging. Here we utilize Raman spectro-microscopy for spatial mapping of metabolites within single cells, with the specific goal of identifying druggable metabolic susceptibilities from a series of patient-derived melanoma cell lines. Each cell line represents a different characteristic level of cancer cell de-differentiation. First, with Raman spectroscopy, followed by stimulated Raman scattering (SRS) microscopy and transcriptomics analysis, we identify the fatty acid synthesis pathway as a druggable susceptibility for differentiated melanocytic cells. We then utilize hyperspectral-SRS imaging of intracellular lipid droplets to identify a previously unknown susceptibility of lipid mono-unsaturation within de-differentiated mesenchymal cells with innate resistance to BRAF inhibition. Drugging this target leads to cellular apoptosis accompanied by the formation of phase-separated intracellular membrane domains. The integration of subcellular Raman spectro-microscopy with lipidomics and transcriptomics suggests possible lipid regulatory mechanisms underlying this pharmacological treatment. Our method should provide a general approach in spatially-resolved single cell metabolomics studies.
Persistent and reversible solid iodine electrodeposition in nanoporous carbons
Authors: Prehal Christian , Fitzek Harald , Kothleitner Gerald , Presser Volker , Gollas Bernhard , Freunberger Stefan A. , Abbas Qamar 
Published: September 2020

AbstractAqueous iodine based electrochemical energy storage is considered a potential candidate to improve sustainability and performance of current battery and supercapacitor technology. It harnesses the redox activity of iodide, iodine, and polyiodide species in the confined geometry of nanoporous carbon electrodes. However, current descriptions of the electrochemical reaction mechanism to interconvert these species are elusive. Here we show that electrochemical oxidation of iodide in nanoporous carbons forms persistent solid iodine deposits. Confinement slows down dissolution into triiodide and pentaiodide, responsible for otherwise significant self-discharge via shuttling. The main tools for these insights are in situ Raman spectroscopy and in situ small and wide-angle X-ray scattering (in situ SAXS/WAXS). In situ Raman confirms the reversible formation of triiodide and pentaiodide. In situ SAXS/WAXS indicates remarkable amounts of solid iodine deposited in the carbon nanopores. Combined with stochastic modeling, in situ SAXS allows quantifying the solid iodine volume fraction and visualizing the iodine structure on 3D lattice models at the sub-nanometer scale. Based on the derived mechanism, we demonstrate strategies for improved iodine pore filling capacity and prevention of self-discharge, applicable to hybrid supercapacitors and batteries.
Stability of heterogeneous single-atom catalysts: a scaling law mapping thermodynamics to kinetics
Authors: Su Ya-Qiong , Zhang Long , Wang Yifan , Liu Jin-Xun , Muravev Valery , Alexopoulos Konstantinos , Filot Ivo A. W. , Vlachos Dionisios G. , Hensen Emiel J. M. 
Published: September 2020

AbstractHeterogeneous single-atom catalysts (SACs) hold the promise of combining high catalytic performance with maximum utilization of often precious metals. We extend the current thermodynamic view of SAC stability in terms of the binding energy (Ebind) of single-metal atoms on a support to a kinetic (transport) one by considering the activation barrier for metal atom diffusion. A rapid computational screening approach allows predicting diffusion barriers for metal–support pairs based on Ebindof a metal atom to the support and the cohesive energy of the bulk metal (Ec). Metal–support combinations relevant to contemporary catalysis are explored by density functional theory. Assisted by machine-learning methods, we find that the diffusion activation barrier correlates with (Ebind)2/Ecin the physical descriptor space. This diffusion scaling-law provides a simple model for screening thermodynamics to kinetics of metal adatom on a support.
Global terrestrial carbon fluxes of 1999–2019 estimated by upscaling eddy covariance data with a random forest
Authors: Zeng Jiye , Matsunaga Tsuneo , Tan Zheng-Hong , Saigusa Nobuko , Shirai Tomoko , Tang Yanhong , Peng Shushi , Fukuda Yoko 
Published: September 2020

AbstractThe terrestrial biosphere is a key player in slowing the accumulation of carbon dioxide in the atmosphere. While quantification of carbon fluxes at global land scale is important for mitigation policy related to climate and carbon, measurements are only available at sites scarcely distributed in the world. This leads to using various methods to upscale site measurements to the whole terrestrial biosphere. This article reports a product obtained by using a Random Forest to upscale terrestrial net ecosystem exchange, gross primary production, and ecosystem respiration from FLUXNET 2015. Our product covers land from −60°S to 80°N with a spatial resolution of 0.1° × 0.1° every 10 days during the period 1999–2019. It was compared with four existing products. A distinguishable feature of our method is using three derived variables of leaf area index to represent plant functional type (PFT) so that measurements from different PFTs can be mixed better by the model. This product can be valuable for the carbon-cycle community to validate terrestrial biosphere models and cross check datasets.
How Alfvén waves induce compressive flows in the neighborhood of a 2.5D magnetic null-point
Authors: Sabri S. , Farahani S. Vasheghani , Ebadi H. , Poedts S. 
Published: September 2020

AbstractThe aim of the present study is to provide insight on the induced compressive perturbations together with the modifications of the environmental parameters in the course of Alfvén wave interaction with a solar magnetic null-point. The shock-capturing Godunov-type code PLUTO is used to solve the set of ideal magnetohydrodynamic equations. The nonlinear effects connected with an initial Alfvén pulse nearing a magnetic null point induces fast and slow magnetoacoustic waves with anti phase conduct. The induced current density and flows are independent of the local plasma-$$\beta$$
β
at the reconnection site. The induced inflows and outflows highly depend on the polarization. The inflows have a stronger effect compared to the outflows in both the x and y directions showing its peak in the x-direction. The dominant wave that couples to flows is the fast wave due to the in-phase harmony between perturbations of the compressive parameters and the fast wave. The induced current density possesses a steady orientation at the reconnection site which governs the diffusion or propagation of the waves. Induced perturbations by the nonlinear forces together with their back reaction on the Alfvén wave have a significant role in the current density excitation being responsible for the creation of inflows and outflows that are possible candidates for the creation of solar jets which has a significant contribution towards coronal seismology.
SET/TAF1 forms a distance-dependent feedback loop with Aurora B and Bub1 as a tension sensor at centromeres
Authors: Asai Yuichiro , Matsumura Rieko , Hasumi Yurina , Susumu Hiroaki , Nagata Kyosuke , Watanabe Yoshinori , Terada Yasuhiko 
Published: September 2020

AbstractDuring mitosis, spatiotemporal regulation of phosphorylation at the kinetochore is essential for accurate chromosome alignment and proper chromosome segregation. Aurora B kinase phosphorylates kinetochore substrates to correct improper kinetochore-microtubule (KT-MT) attachments, whereas tension across the centromeres inactivates Aurora B kinase, and PP2A phosphatase dephosphorylates the kinetochore proteins to stabilize the attachments. However, the molecular entity of the tension sensing mechanism remains elusive. In a previous report, we showed that centromeric SET/TAF1 on Sgo2 up-regulates Aurora B kinase activity via PP2A inhibition in prometaphase. Here we show that Aurora B and Bub1 at the centromere/kinetochore regulate both kinase activities one another in an inter-kinetochore distance-dependent manner, indicating a positive feedback loop. We further show that the centromeric pool of SET on Sgo2 depends on Bub1 kinase activity, and the centromeric localization of SET decreases in a distance-dependent manner, thereby inactivating Aurora B in metaphase. Consistently, ectopic targeting of SET to the kinetochores during metaphase hyperactivates Aurora B via PP2A inhibition, and thereby rescues the feedback loop. Thus, we propose that SET, Aurora B and Bub1 form a distance-dependent positive feedback loop, which spatiotemporally may act as a tension sensor at centromeres.
Sodium nitrate co-supplementation does not exacerbate low dose metronomic doxorubicin-induced cachexia in healthy mice
Authors: Campelj Dean G. , Debruin Danielle A. , Timpani Cara A. , Hayes Alan , Goodman Craig A. , Rybalka Emma 
Published: September 2020

AbstractThe purpose of this study was to determine whether (1) sodium nitrate (SN) treatment progressed or alleviated doxorubicin (DOX)-induced cachexia and muscle wasting; and (2) if a more-clinically relevant low-dose metronomic (LDM) DOX treatment regimen compared to the high dosage bolus commonly used in animal research, was sufficient to induce cachexia in mice. Six-week old male Balb/C mice (n = 16) were treated with three intraperitoneal injections of either vehicle (0.9% NaCl; VEH) or DOX (4 mg/kg) over one week. To test the hypothesis that sodium nitrate treatment could protect against DOX-induced symptomology, a group of mice (n = 8) were treated with 1 mM NaNO3 in drinking water during DOX (4 mg/kg) treatment (DOX + SN). Body composition indices were assessed using echoMRI scanning, whilst physical and metabolic activity were assessed via indirect calorimetry, before and after the treatment regimen. Skeletal and cardiac muscles were excised to investigate histological and molecular parameters. LDM DOX treatment induced cachexia with significant impacts on both body and lean mass, and fatigue/malaise (i.e. it reduced voluntary wheel running and energy expenditure) that was associated with oxidative/nitrostative stress sufficient to induce the molecular cytotoxic stress regulator, nuclear factor erythroid-2-related factor 2 (NRF-2). SN co-treatment afforded no therapeutic potential, nor did it promote the wasting of lean tissue. Our data re-affirm a cardioprotective effect for SN against DOX-induced collagen deposition. In our mouse model, SN protected against LDM DOX-induced cardiac fibrosis but had no effect on cachexia at the conclusion of the regimen.
Network Hamiltonian models reveal pathways to amyloid fibril formation
Authors: Yu Yue , Grazioli Gianmarc , Unhelkar Megha H. , Martin Rachel W. , Butts Carter T. 
Published: September 2020

AbstractAmyloid fibril formation is central to the etiology of a wide range of serious human diseases, such as Alzheimer’s disease and prion diseases. Despite an ever growing collection of amyloid fibril structures found in the Protein Data Bank (PDB) and numerous clinical trials, therapeutic strategies remain elusive. One contributing factor to the lack of progress on this challenging problem is incomplete understanding of the mechanisms by which these locally ordered protein aggregates self-assemble in solution. Many current models of amyloid deposition diseases posit that the most toxic species are oligomers that form either along the pathway to forming fibrils or in competition with their formation, making it even more critical to understand the kinetics of fibrillization. A recently introduced topological model for aggregation based on network Hamiltonians is capable of recapitulating the entire process of amyloid fibril formation, beginning with thousands of free monomers and ending with kinetically accessible and thermodynamically stable amyloid fibril structures. The model can be parameterized to match the five topological classes encompassing all amyloid fibril structures so far discovered in the PDB. This paper introduces a set of network statistical and topological metrics for quantitative analysis and characterization of the fibrillization mechanisms predicted by the network Hamiltonian model. The results not only provide insight into different mechanisms leading to similar fibril structures, but also offer targets for future experimental exploration into the mechanisms by which fibrils form.
Optimization for maximum specific energy density of a lithium-ion battery using progressive quadratic response surface method and design of experiments
Authors: Kim Ji-San , Lee Dong-Chan , Lee Jeong-Joo , Kim Chang-Wan 
Published: September 2020

AbstractThe demand for high-capacity lithium-ion batteries (LIB) in electric vehicles has increased. In this study, optimization to maximize the specific energy density of a cell is conducted using the LIB electrochemical model and sequential approximate optimization (SAO). First, the design of experiments is performed to analyze the sensitivity of design factors important to the specific energy density, such as electrode and separator thicknesses, porosity, and particle size. Then, the design variables of the cell are optimized for maximum specific energy density using the progressive quadratic response surface method (PQRSM), which is one of the SAO techniques. As a result of optimization, the thickness ratio of the electrode was optimized and the porosity was reduced to keep the specific energy density high, while still maintaining the specific power density performance. This led to an increase in the specific energy density of 56.8% and a reduction in the polarization phenomenon of 11.5%. The specific energy density effectively improved through minimum computation despite the nonlinearity of the electrochemical model in PQRSM optimization.
Helicobacter pylori infection induces STAT3 phosphorylation on Ser727 and autophagy in human gastric epithelial cells and mouse stomach
Authors: Piao Juan-Yu , Kim Su-Jung , Kim Do-Hee , Park Ji Hyun , Park Sin-Aye , Han Hyeong-jun , Na Hye-Kyung , Yoon Kichul , Lee Ha-Na , Kim Nayoung , Hahm Ki Baik , Surh Young-Joon 
Published: September 2020

AbstractHelicobacter pylori (H. pylori) infection is considered as one of the principal risk factors of gastric cancer. Constitutive activation of the signal transducer and activator of transcription 3 (STAT3) plays an important role in inflammation-associated gastric carcinogenesis. In the canonical STAT3 pathway, phosphorylation of STAT3 on Tyr705 is a major event of STAT3 activation. However, recent studies have demonstrated that STAT3 phosphorylated on Ser727 has an independent function in mitochondria. In the present study, we found that human gastric epithelial AGS cells infected with H. pylori resulted in localization of STAT3 phosphorylated on Ser727 (P-STAT3Ser727), predominantly in the mitochondria. Notably, H. pylori-infected AGS cells exhibited the loss of mitochondrial integrity and increased expression of the microtubule-associated protein light chain 3 (LC3), the autophagosomal membrane-associated protein. Treatment of AGS cells with a mitophagy inducer, carbonyl cyanide 3-chlorophenylhydrazone (CCCP), resulted in accumulation of P-STAT3Ser727 in mitochondria. In addition, the elevated expression and mitochondrial localization of LC3 induced by H. pylori infection were attenuated in AGS cells harboring STAT3 mutation defective in Ser727 phosphorylation (S727A). We also observed that both P-STAT3Ser727 expression and LC3 accumulation were increased in the mitochondria of H. pylori-inoculated mouse stomach.
Ontogeny of different subsets of yellow fever virus-specific circulatory CXCR5+ CD4+ T cells after yellow fever vaccination
Authors: DeGottardi Quinn , Gates Theresa J. , Yang Junbao , James Eddie A. , Malhotra Uma , Chow I-Ting , Simoni Yannick , Fehlings Michael , Newell Evan W. , DeBerg Hannah A. , Kwok William W. 
Published: September 2020

AbstractMonitoring the frequency of circulatory CXCR5+ (cCXCR5+) CD4+ T cells in periphery blood provides a potential biomarker to draw inferences about T follicular helper (TFH) activity within germinal center. However, cCXCR5+ T cells are highly heterogeneous in their expression of ICOS, PD1 and CD38 and the relationship between different cCXCR5 subsets as delineated by these markers remains unclear. We applied class II tetramer reagents and mass cytometry to investigate the ontogeny of different subsets of cCXCR5+ T cell following yellow fever immunization. Through unsupervised analyses of mass cytometry data, we show yellow fever virus-specific cCXCR5 T cells elicited by vaccination were initially CD38+ICOS+PD1+, but then transitioned to become CD38+ICOS−PD1+ and CD38−ICOS−PD1+ before coming to rest as a CD38−ICOS−PD1− subset. These results imply that most antigen-specific cCXCR5+ T cells, including the CD38−ICOS−PD1− CXCR5+ T cells are derived from the CXCR5+CD38+ICOS+PD1+ subset, the subset that most resembles preTFH/TFH in the germinal center.