bluuebunny/crossref_metadata_2025_split huggingface dataset:
Present and future changes in precipitation characteristics during Indian summer monsoon in CORDEX‐CORE simulations
Authors: Maharana Pyarimohan , Kumar Dhirendra , Das Sushant , Tiwari Pushp Raj 
Published: December 2020

AbstractThis work examines the changes in precipitation characteristics over the Indian region using the latest high‐resolution CORDEX‐CORE model simulations. Individual RCM (COSMO, RegCM4.7, and REMO) experiments, their ensembles, and all RCM ensembles are examined to evaluate their performance using various statistical metrics. It aims to provide a holistic idea for choosing better models for specific analysis (variability, climatology, temporal evolution, indices, etc.) of precipitation distribution over India. The COSMO model experiments show lesser mean bias and have a high correlation coefficient (>0.8) compared to REMO and RegCM4. Each RCM ensemble performs better than its members in representing the spatial patterns of precipitation. Interestingly, the RCM experiments downscaling the forcings from MPI_ESM GCMs and ERA‐Interim outperforms other RCM experiments in the present day period. The probability distribution function reflects that the mean frequency and the intensity of precipitation are best represented in the RegCM4 ensemble. Further, most RCMs agree to a robust increase in low‐intensity rainfall (>0.1–4 mm⋅day‑1) in the future under the RCP8.5 scenario. The intraseasonal variability in terms of active and break spells are best represented in the RegCM4 ensemble. There exists uncertainty in terms of projection of active phases, while all model experiments agree to the decrease in the break phases in the near future compared to the present day. The projected consecutive dry (wet) days and their spells will decrease (increase) over India. The heavy precipitation events are expected to increase (by 18–32 days) along with its contribution (by 14–48%) towards the total precipitation over entire India indicating a possible increase in flooding events in the future. The present‐day ISM characteristics is well captured in the model ensemble compared to individual experiments. The model ensemble indicates towards a robust increase in low‐intensity rainfall in the future. The very heavy precipitation events and its contribution towards total precipitation are increasing in the future.
Enantioseparation of ondansetron by countercurrent chromatography using sulfobutyl ether‐β‐cyclodextrin as chiral selector
Authors: Sun Wenyu , Bao Honglei , Qian Junqing , Tong Shengqiang 
Published: December 2020

AbstractOndansetron, a highly selective 5‐hydroxytryptamine 3 receptor antagonist, was successfully enantioseparated by recycling countercurrent chromatography using sulfobutyl ether‐β‐cyclodextrin as chiral selector. Important factors for the enantioseparation were optimized, including different organic solvent, type of substituted β‐cyclodextrin, pH of aqueous phase, concentration of chiral selector, and separation temperature. A biphasic solvent system composed of n‐hexane: n‐butyl acetate: 0.1 mol/L phosphate buffer solution pH 9.2 with 50 mmol/L of sulfobutyl ether‐β‐cyclodextrin (2.5:7.5:10, v/v/v) was selected. Under optimized separation conditions, 5 mg of ondansetron was enantioseparated using recycling countercurrent chromatography, yielding 1.2 and 1.5 mg of ondansetron enantiomers with 97.5 and 95.8% purity and the recovery reached 48–60%.
Hybrid Curdlan Poly(γ ‐Glutamic Acid) Nanoassembly for Immune Modulation in Macrophage
Authors: Heo Jeongyun , Sobiech Thomas A. , Kutscher Hilliard L. , Chaves Lee , Sukumaran Dinesh K. , Karki Shanta , Dube Admire , Prasad Paras N. , Reynolds Jessica L. 
Published: December 2020

AbstractA nanoformulation composed of curdlan, a linear polysaccharide of 1,3‐β‐linked d‐glucose units, hydrogen bonded to poly(γ ‐glutamic acid) (PGA), was developed to stimulate macrophage. Curdlan/PGA nanoparticles (C‐NP) are formulated by physically blending curdlan (0.2 mg mL−1 in 0.4 m NaOH) with PGA (0.8 mg mL−1). Forster resonance energy transfer (FRET) analysis demonstrates a heterospecies interpolymer complex formed between curdlan and PGA. The 1H‐NMR spectra display significant peak broadening as well as downfield chemical shifts of the hydroxyl proton resonances of curdlan, indicating potential intermolecular hydrogen bonding interactions. In addition, the cross peaks in 1H‐1H 2D‐NOESY suggest intermolecular associations between the OH‐2/OH‐4 hydroxyl groups of curdlan and the carboxylic‐/amide‐groups of PGA via hydrogen bonding. Intracellular uptake of C‐NP occurs over time in human monocyte‐derived macrophage (MDM). Furthermore, C‐NP nanoparticles dose‐dependently increase gene expression for TNF‐α, IL‐6, and IL‐8 at 24 h in MDM. C‐NP nanoparticles also stimulate the release of IL‐lβ, MCP‐1, TNF‐α, IL‐8, IL‐12p70, IL‐17, IL‐18, and IL‐23 from MDM. Overall, this is the first demonstration of a simplistic nanoformulation formed by hydrogen bonding between curdlan and PGA that modulates cytokine gene expression and release of cytokines from MDM.
M2‐like tumor‐associated macrophages‐secreted Wnt1 and Wnt3a promotes dedifferentiation and metastasis via activating β‐catenin pathway in thyroid cancer
Authors: Lv Juan , Feng Zhi‐Ping , Chen Fu‐Kun , Liu Chao , Jia Li , Liu Peng‐Jie , Yang Chuan‐Zhou , Hou Fei , Deng Zhi‐Yong 
Published: December 2020

AbstractBackgroundThyroid carcinoma (TC) has been a global issue for its rapid increasing incidence worldwide. Although most TC was not so aggressive with a good prognosis, treatment against anaplastic TC was relatively limited and the mechanisms are not well elucidated yet.MethodsTC cell lines (IHH4 and TPC‐1) were used. Flow cytometry was used to identify the surface marker of M2‐like tumor‐associated macrophages (TAMs) from cell culture. Quantitative real‐time polymerase chain reaction, western blot analysis, immunostaining, and immunohistochemistry were used to detect the expression of Wnt1, Wnt3a, components of Wnt/β‐catenin pathway, and proliferation/epithelial–mesenchymal transition (EMT)‐related proteins. Alkaline phosphatase activity assay, colony formation assay, and transwell assay were used to examine the roles of Wnt1, Wnt3a, and β‐catenin pathway in cell dedifferentiation, proliferation, migration, and invasion of TC cells, respectively. Subcutaneous tumor growth was monitored in nude mice.ResultsCoculture with M2‐like TAMs facilitated dedifferentiation, proliferation, migration, and invasion in TC cells. EMT and proliferation‐related proteins were also promoted in cocultured TC cells. The level of Wnt1 and Wnt3a was increased in the coculture system. Block of Wnt1 or Wnt3a suppressed malignant behaviors in cocultured tumor cells. Furthermore, Wnt1 or Wnt3a knockdown inhibited Wnt/β‐catenin signaling pathway, and suppressed EMT and proliferation‐related signals in cocultured tumor cells. Knockdown of Wnt1 or Wnt3a inhibited tumor growth in xenograft model.ConclusionM2‐like TAMs promoted dedifferentiation, proliferation, and metastasis of TC by Wnt1 and Wnt3a secretion and ensuing β‐catenin activation.
Association of RANK and RANKL gene polymorphism with survival and calcium levels in multiple myeloma
Authors: Łacina Piotr , Butrym Aleksandra , Humiński Michał , Dratwa Marta , Frontkiewicz Diana , Mazur Grzegorz , Bogunia‐Kubik Katarzyna 
Published: December 2020

AbstractMultiple myeloma (MM) is a heterogeneous bone marrow cancer characterized by proliferation of malignant plasma cells in the bone marrow. One of its major symptoms are hypercalcaemia and bone lesions, which may result in pathologic bone fractures. Receptor activator for nuclear factor κB (RANK) and its ligand, RANKL, are part of an activation pathway for osteoclasts and are thus responsible for bone resorption. Furthermore, RANKL expression is increased in multiple myeloma. In the present study, we investigated the role of single nucleotide polymorphisms (SNPs) in the genes coding for RANK (rs1805034, rs8086340), RANKL (rs7325635, rs7988338), and TACI (rs34562254), a receptor for osteoclast‐derived pro‐survival factors. The study involved 222 patients and 222 healthy individuals, and the analysis included disease susceptibility, survival, bone lesions, calcium levels, and vascular endothelial growth factor levels. Patients with allele RANK rs1805034 C had higher survival (p = .003). This relationship was especially evident in women (p = .006). Furthermore, allele rs1805034 C was associated with slightly lower median age at diagnosis (64.0 vs. 65.5, p = .008). Allele RANKL rs7325635 A correlated with lower progression‐free survival (p = .027), and with lack of early progression (p = .023). Additionally, women with allele rs7325635 G were found to have higher calcium blood concentration (p = .040). Allele TACI rs34562254 A was more common in MM patients in more advanced stages (II and III stage International Staging System) at diagnosis (p = .017), and the SNP showed a slight trend towards association in a multivariate analysis (p = .084). Taken together, our results suggest that RANK rs1805034 and RANKL rs7325635 may have a role in MM development and progression.
Focal adhesion kinase (FAK) inhibitor‐defactinib suppresses the malignant progression of human esophageal squamous cell carcinoma (ESCC) cells via effective blockade of PI3K/AKT axis and downstream molecular network
Authors: Zhang Lingyuan , Zhao Di , Wang Yan , Zhang Weimin , Zhang Jing , Fan Jiawen , Zhan Qimin , Chen Jie 
Published: December 2020

AbstractThe clinical therapeutic efficacy toward esophageal squamous cell carcinoma (ESCC) is undesirable, due to the lack of targeted agents. Focal adhesion kinase (FAK), a nonreceptor tyrosine kinase involved in multiple fields of tumorigenesis, recently has been indicated as a promising therapeutic target in ESCC treatment. Here, we revealed that defactinib, a specific FAK inhibitor, effectively suppressed the malignancy of ESCC cells. Mechanistically, defactinib dose and time‐dependently induced the dissociation of phosphoinositide‐3‐kinase (PI3K) from FAK, resultantly led to blockade of protein kinase B (AKT) signaling, and the expression of several oncogenes, such as SOX2, MYC, EGFR, MET, MDM2, or TGFBR2, identified by microarray and real‐time polymerase chain reaction assay. Specifically, this FAK inhibition‐mediated suppression of PI3K/AKT signaling and downstream ESCC specific biomarkers was maintained to 24 h in in vitro experiments to guarantee the treatment durability and efficacy. Importantly, defactinib suppressed tumor growth, metastatic ability, and increased overall survival of xenografted animals without producing significantly systematic toxicity. Our data suggest that FAK inhibition provides an excellent targeted therapy toward ESCC by effectively inhibiting PI3K/AKT pathway and downstream molecular network.
Striped Mullet Migration Patterns in the Indian River Lagoon: A Network Analysis Approach to Spatial Fisheries Management
Authors: Myers Olivia M. , Reyier Eric , Ahr Bonnie , Cook Geoffrey S. 
Published: December 2020

Abstract
Striped Mullet Mugil cephalus are numerically abundant forage fish, highly valuable as prey, and commercially valuable to humans. From September to December, Striped Mullet in the Indian River Lagoon (IRL), Florida, undergo an annual migration from inshore foraging habitats to oceanic spawning sites. However, their migratory pathways—particularly their intra-estuarine movement pathways—remain unknown. To address this knowledge gap, we utilized passive acoustic telemetry to assess the movement patterns of Striped Mullet within the IRL. Thirty-two fish were tagged, generating usable tracks from 18 individuals. The mean (±SD) time that fish were detected in the array was about 38 ± 90 d, with the longest detection period being 444 d. We also document the first evidence of skipped spawning in Striped Mullet inhabiting waters of the southeastern United States. These data suggest that impoundments around the Merritt Island National Wildlife Refuge serve as important refugia for Striped Mullet, while the Banana and Indian rivers act as corridors during their inshore migratory movements. Through spatial fisheries management, high-value habitat and connective elements utilized by Striped Mullet and other vital forage fish may be identified so as to benefit both natural and human dynamics in estuarine systems.
Targeting Expanded Repeats by Small Molecules in Repeat Expansion Disorders
Authors: Nakamori Masayuki , Mochizuki Hideki 
Published: December 2020

ABSTRACTRecent technological advancements in genetic analysis have allowed for the consecutive discovery and elucidation of repeat expansion disorders: diseases caused by the abnormal expansion of repeat sequences in the genome. Many of these repeat expansion disorders are neurodegenerative movement disorders. Radical cures for these disorders have yet to be established. Although conventional treatments for repeat expansion disorders have mainly targeted the abnormal mRNA and proteins encoded by the affected genes, therapeutic approaches targeting repeat DNA, the root cause of repeat disorders, is also being explored in current research. In particular, a small molecule has been found that binds to abnormally expanded CAG repeats, the cause of Huntington's disease, and shortens them. Such small molecules targeting nucleic acids are expected to be developed into groundbreaking therapeutic drugs capable of ameliorating the symptoms of repeat expansion disorders and preventing their onset. © 2020 International Parkinson and Movement Disorder Society
Chemoinformatics for the Safety of Energetic and Reactive Materials at Ineris
Authors: Fayet Guillaume , Rotureau Patricia 
Published: December 2020

AbstractThe characterization of physical hazards of substances is a key information to manage the risks associated to their use, storage and transport. With decades of work in this area, Ineris develops and implements cutting‐edge experimental facilities allowing such characterizations at different scales and under various conditions to study all of the dreaded accident scenarios. This review presents the efforts engaged by Ineris more recently in the field of chemoinformatics to develop and use new predictive methods for the anticipation and management of industrials risks associated to energetic and reactive materials as a complement to experiments.An overview of the methods used for the development of Quantitative Structure‐Property Relationships for physical hazards are presented and discussed regarding the specificities associated to this class of properties. A review of models developed at Ineris is also provided from the first tentative models on the explosivity of nitro compounds to the successful application to the flammability of organic mixtures. Then, a discussion is proposed on the use of QSPR models. Good practices for robust use for QSPR models are recalled with specific comments related to physical hazards, notably for regulatory purpose. Dissemination and training efforts engaged by Ineris are also presented. The potential offered by these predictive methods in terms of in silico design and for the development of new intrinsically safer technologies in safety‐by‐design strategies is finally discussed. At last, challenges and perspectives to extend the application of chemoinformatics in the field of safety and in particular for the physical hazards of energetic and reactive substances are proposed.
A Benchmark for automatic noise measurement in clinical computed tomography
Authors: Ahmad Moiz , Jacobsen Megan C. , Thomas M. Allan , Chen Henry S. , Layman Rick R. , Jones A. Kyle 
Published: December 2020

PurposeAssessment of image quality directly in clinical image data is an important quality control objective as phantom‐based testing does not fully represent image quality across patient variation. Computer algorithms for automatically measuring noise in clinical computed tomography (CT) images have been introduced, but the accuracy of these algorithms is unclear. This work benchmarks the accuracy of the global noise (GN) algorithm for automatic noise measurement in contrast‐enhanced abdomen CT exams in comparison to precise reference noise measurements. The GN algorithm was further optimized compared to the previous report in the literature.MethodsReference values of noise were established in a public image dataset of 82 contrast‐enhanced abdomen CT exams. The reference noise values were obtained by manual regions‐of‐interest measurements of pixel standard deviation in the liver parenchyma according to an instruction protocol. Noise measurements taken by six observers were averaged together to improve reference noise statistical precision. The GN algorithm was used to automatically measure noise in each image set. The accuracy of the GN algorithm was determined in terms of RMS error compared to reference noise. The GN algorithm was optimized by conducting 1000 trials with random algorithm parameter values. The trial with the lowest RMS error was used to select optimum algorithm parameters.ResultsThe range of noise across CT image sets was 8.8–28.8 HU. Reference noise measurements were made with a precision of ±0.78 HU (95% confidence interval). The RMS error of automatic noise measurement was 0.93 HU (0.77–1.19 HU 95% confidence interval). The automatic noise measurements were equally accurate across image sets of varying noise magnitude. Optimum GN algorithm parameter values were: a kernel size of 7 pixels, and soft tissue lower and upper thresholds of 0 and 170 HU, respectively.ConclusionsThe performance of automatic noise measurement was benchmarked in a large clinical CT dataset. The study provides a framework for thorough validation of automatic clinical image quality measurement methods. The GN algorithm was optimized and validated for automatic measurement of soft‐tissue noise in abdomen CT exams.
Optimization of a calibration phantom for quantitative radiography
Authors: Martinez Cristobal , de Molina Claudia , Desco Manuel , Abella Monica 
Published: December 2020

ObjectiveDual energy radiography (DER) makes it possible to obtain separate images for soft‐tissue and bony structures (tissue maps) based on the acquisition of two radiographs at different source peak‐kilovoltage values. Current DER studies are based on the weighted subtraction method, which requires either manual tuning or the use of precomputed tables, or on decomposition methods, which make use of a calibration to model soft‐tissue and bone components. In this study, we examined in depth the optimum method to perform this calibration.MethodsWe used simulations to optimize the calibration protocol and evaluated the effect of the material and size of a calibration phantom composed of two wedges and its positioning in the system. Evaluated materials were water, PMMA and A‐150 as soft‐tissue equivalent, and Teflon, B‐100 and aluminum as bone equivalent, with sizes from 5 to 30 cm. Each material combination was compared with an ideal phantom composed of soft tissue and bone. Our simulation results enabled us to propose four designs that were tested with the NOVA FA X‐ray system with a realistic thorax phantom.ResultsCalibration based on a very simple and inexpensive phantom with no strict requirements in its placement results in appropriate separation of the spine (a common focus in densitometry studies) and the identification of nodules as small as 6 mm, which have been reported to have a low rate of detection in radiography.ConclusionThe proposed method is completely automatic, avoiding the need for a radiology technician with expert knowledge of the protocol, as is the case in densitometry exams. The method provides real mass thickness values, enabling quantitative planar studies instead of relative comparisons.
High‐resolution metabolic mapping of the cerebellum using 2D zoom magnetic resonance spectroscopic imaging
Authors: Emir Uzay E. , Sood Jaiyta , Chiew Mark , Thomas Micheal Albert , Lane Sean P. 
Published: December 2020

PurposeThe human cerebellum plays an important role in the functional activity of the cerebrum, ranging from motor to cognitive systems given its relaying role between the spinal cord and cerebrum. The cerebellum poses many challenges to Magnetic Resonance Spectroscopic Imaging (MRSI) due to its caudal location, susceptibility to physiological artifacts, and partial volume artifacts resulting from its complex anatomical structure. Thus, in the present study, we propose a high‐resolution MRSI acquisition scheme for the cerebellum.MethodsA zoom or reduced field of view (rFOV) metabolite‐cycled MRSI acquisition at 3 Tesla, with a grid of 48 × 48, was developed to achieve a nominal resolution of 62.5 μL. Single‐slice rFOV MRSI data were acquired from the cerebellum of 5 healthy subjects with a nominal resolution of 2.5 × 2.5 × 10 mm3 in 9.6 min. Spectra were quantified using the LCModel package. A spatially unbiased atlas template of the cerebellum was used to analyze metabolite distributions in the cerebellum.ResultsThe superior quality of the achieved spectra‐enabled generation of high‐resolution metabolic maps of total N‐acetylaspartate, total Creatine (tCr), total Choline (tCho), glutamate+glutamine, and myo‐inositol, with Cramér‐Rao lower bounds below 50%. A template‐based regions of interest (ROI) analysis resulted in spatially dependent metabolite distributions in 9 ROIs. The group‐averaged high‐resolution metabolite maps across subjects increased the contrast‐to‐noise ratio between cerebellum regions.ConclusionThese findings indicate that very high‐resolution metabolite probing of the cerebellum is feasible using rFOV or zoomed MRSI at 3 Tesla.
Recent advances of high performance magnetic iron oxide nanoparticles: Controlled synthesis, properties tuning and cancer theranostics
Authors: Liang Yi‐Jun , Xie Jun , Yu Jing , Zheng Zhaoguang , Liu Fang , Yang Anping 
Published: December 2020

AbstractRecently, magnetic nanomaterials have emerged as multifunctional materials for a wide range of biomedical applications. Functional magnetic iron oxide nanoparticles (FMIONs) are typical magnetic nanomaterials with inherent advantages for disease diagnosis, prevention, and treatment: high specific surface area, excellent superparamagnetism, good colloidal stability, and remarkable biosafety. Therefore, FMION‐based biomedicine has advanced at an unprecedented rate in recent years. However, the performance of FMIONs cannot yet meet complicated physiological circumstances. To overcome these limitations, researchers have designed and manipulated the geometric shapes, sizes, compositions, and surfaces to endow these FMIONs with high performance. This review summarizes recent advances in the controlled synthesis of FMIONs, cover corresponding theories of nucleation and growth in solution, and the tuning of FMION properties for disease diagnosis and therapy. After discussing the biomedical applications in cancer theranostics—tumor hyperthermia, magnetic resonance imaging and drug delivery system—in detail, the review concludes with current challenges and outlooks for the development of FMIONs.