bluuebunny/crossref_metadata_2025_split huggingface dataset:
Triphenylphosphonium (TPP)‐Based Antioxidants: A New Perspective on Antioxidant Design
Authors: Wang Jiayao Y. , Li Jiaqi Q. , Xiao Yumei M. , Fu Bin , Qin Zhaohai H. 
Published: February 2020

AbstractMitochondrial oxidative damage and dysfunction contribute to a wide range of human diseases. Considering the limitation of conventional antioxidants and that mitochondria are the main source of reactive oxygen species (ROS) which induce oxidative damage, mitochondria‐targeted antioxidants which can selectively block mitochondrial oxidative damage and prevent various types of cell death have been widely developed. As a lipophilic cation, triphenylphosphonium (TPP) has been commonly used in designing mitochondria‐targeted antioxidants. Conjugated with the TPP moiety, antioxidants can achieve more than 1000‐fold higher mitochondrial concentration depending on cell membrane potentials and mitochondrial membrane potentials. Herein we discuss the deficiencies of conventional antioxidants and the advantages of mitochondrial targeting, and review various types of TPP‐based mitochondria‐targeted antioxidants. These provide theoretical and background support for the design of new anti‐oxidant.
Design, Synthesis, and Pharmacological Evaluation of First‐in‐Class Multitarget N‐Acylhydrazone Derivatives as Selective HDAC6/8 and PI3Kα Inhibitors
Authors: Rodrigues Daniel A. , Guerra Fabiana S. , Sagrillo Fernanda S. , de Sena M. Pinheiro Pedro , Alves Marina A. , Thota Sreekanth , Chaves Lorrane S. , Sant'Anna Carlos M. R. , Fernandes Patrícia D. , Fraga Carlos A. M. 
Published: February 2020

AbstractTargeting histone deacetylases (HDACs) and phosphatidylinositol 3‐kinases (PI3Ks) is a very promising approach for cancer treatment. This manuscript describes the design, synthesis, in vitro pharmacological profile, and molecular modeling of a novel class of N‐acylhydrazone (NAH) derivatives that act as HDAC6/8 and PI3Kα dual inhibitors. The surprising selectivity for PI3Kα may be related to differences in the conformation in the active site. Cellular studies showed that these compounds act in HDAC6 inhibition and the PI3/K/AKT/mTOR pathway. The compounds that are selective for inhibition of HDAC6/8 and inhibit PI3Kα show potential for the treatment of cancer.
A randomized, phase 1, placebo‐controlled trial of APG‐157 in oral cancer demonstrates systemic absorption and an inhibitory effect on cytokines and tumor‐associated microbes
Authors: Basak Saroj K. , Bera Alakesh , Yoon Alexander J. , Morselli Marco , Jeong Chan , Tosevska Anela , Dong Tien S. , Eklund Michael , Russ Eric , Nasser Hassan , Lagishetty Venu , Guo Rong , Sajed Dipti , Mudgal Sharmila , Mehta Parag , Avila Luis , Srivastava Meera , Faull Kym , Jacobs Jonathan , Pellegrini Matteo , Shin Daniel Sanghoon , Srivatsan Eri S. , Wang Marilene B. 
Published: February 2020

BackgroundAlthough curcumin's effect on head and neck cancer has been studied in vitro and in vivo, to the authors' knowledge its efficacy is limited by poor systemic absorption from oral administration. APG‐157 is a botanical drug containing multiple polyphenols, including curcumin, developed under the US Food and Drug Administration's Botanical Drug Development, that delivers the active components to oromucosal tissues near the tumor target.MethodsA double‐blind, randomized, placebo‐controlled, phase 1 clinical trial was conducted with APG‐157 in 13 normal subjects and 12 patients with oral cancer. Two doses, 100 mg or 200 mg, were delivered transorally every hour for 3 hours. Blood and saliva were collected before and 1 hour, 2 hours, 3 hours, and 24 hours after treatment. Electrocardiograms and blood tests did not demonstrate any toxicity.ResultsTreatment with APG‐157 resulted in circulating concentrations of curcumin and analogs peaking at 3 hours with reduced IL‐1β, IL‐6, and IL‐8 concentrations in the salivary supernatant fluid of patients with cancer. Salivary microbial flora analysis showed a reduction in Bacteroidetes species in cancer subjects. RNA and immunofluorescence analyses of tumor tissues of a subject demonstrated increased expression of genes associated with differentiation and T‐cell recruitment to the tumor microenvironment.ConclusionsThe results of the current study suggested that APG‐157 could serve as a therapeutic drug in combination with immunotherapy.Lay Summary

Curcumin has been shown to suppress tumor cells because of its antioxidant and anti‐inflammatory properties. However, its effectiveness has been limited by poor absorption when delivered orally.

Subjects with oral cancer were given oral APG‐157, a botanical drug containing multiple polyphenols, including curcumin. Curcumin was found in the blood and in tumor tissues. Inflammatory markers and Bacteroides species were found to be decreased in the saliva, and immune T cells were increased in the tumor tissue.

APG‐157 is absorbed well, reduces inflammation, and attracts T cells to the tumor, suggesting its potential use in combination with immunotherapy drugs.
Core needle biopsy versus incisional biopsy for differentiation of soft‐tissue sarcomas: A systematic review and meta‐analysis
Authors: Birgin Emrullah , Yang Cui , Hetjens Svetlana , Reissfelder Christoph , Hohenberger Peter , Rahbari Nuh N. 
Published: February 2020

BackgroundControversies exist regarding the biopsy technique of choice for the accurate diagnosis of soft‐tissue sarcoma (STS). The objective of this systematic review and meta‐analysis was to compare the diagnostic accuracy of core needle biopsy (CNB) versus incisional biopsy (IB) in STS with reference to the final histopathological result.MethodsStudies regarding the diagnostic accuracy of CNB and IB in detecting STS were searched systematically in the MEDLINE and EMBASE databases. Estimates of sensitivity and specificity with associated 95% CIs for diagnostic accuracy were calculated. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies version 2 (QUADAS‐2).ResultsA total of 17 studies comprising 2680 patients who underwent 1582 CNBs and 241 IBs with subsequent tumor resection met the inclusion criteria. The sensitivity and specificity of CNB and IB to detect the dignity of lesions were 97% (95% CI, 95%‐98%) and 99% (95% CI, 97%‐99%), respectively, and 96% (95% CI, 92%‐99%) and 100% (95% CI, 94%‐100%), respectively. Estimates of the sensitivity and specificity of CNB and IB to detect the STS histotype were 88% (95% CI, 86%‐90%) and 77% (95% CI, 72%‐81%), respectively, and 93% (95% CI, 87%‐97%) and 65% (95% CI, 49%‐78%), respectively. Patients who underwent CNB had a significantly reduced risk of complications compared with patients who underwent IB (risk ratio, 0.14; 95% CI, 0.03‐0.56 [P ≤ .01). Quality assessment of studies revealed a high risk of bias.ConclusionsCNB has high accuracy in diagnosing the dignity of lesions and STS histotype in patients with suspected STS with fewer complications compared with IB. Therefore, CNB should be regarded as the primary biopsy technique.
A comparative analysis of the dopaminergic innervation of the executive caudal nidopallium in pigeon, chicken, zebra finch, and carrion crow
Authors: von Eugen Kaya , Tabrik Sepideh , Güntürkün Onur , Ströckens Felix 
Published: February 2020

AbstractDespite the long, separate evolutionary history of birds and mammals, both lineages developed a rich behavioral repertoire of remarkably similar executive control generated by distinctly different brains. The seat for executive functioning in birds is the nidopallium caudolaterale (NCL) and the mammalian equivalent is known as the prefrontal cortex (PFC). Both are densely innervated by dopaminergic fibers, and are an integration center of sensory input and motor output. Whereas the variation of the PFC has been well documented in different mammalian orders, we know very little about the NCL across the avian clade. In order to investigate whether this structure adheres to species‐specific variations, this study aimed to describe the trajectory of the NCL in pigeon, chicken, carrion crow and zebra finch. We employed immunohistochemistry to map dopaminergic innervation, and executed a Gallyas stain to visualize the dorsal arcopallial tract that runs between the NCL and the arcopallium. Our analysis showed that whereas the trajectory of the NCL in the chicken is highly comparable to the pigeon, the two Passeriformes show a strikingly different pattern. In both carrion crow and zebra finch, we identified four different subareas of high dopaminergic innervation that span the entire caudal forebrain. Based on their sensory input, motor output, and involvement in dopamine‐related cognitive control of the delineated areas here, we propose that at least three morphologically different subareas constitute the NCL in these songbirds. Thus, our study shows that comparable to the PFC in mammals, the NCL in birds varies considerably across species.
Isolation of Highly Migratory and Invasive Cells in Three‐Dimensional Gels
Authors: Takino Takahisa , Suzuki Takeshi , Seiki Motoharu 
Published: February 2020

AbstractWe developed a modified invasion assay in three‐dimensional (3D) gels that permits isolation of invading cells as living cells, termed an invading cell–trapping (iCT) assay. A small cell strainer consisting of nylon mesh with pores of 40‐µm square is used in this assay. A layer of gel composed of extracellular‐matrix components is formed on each side of the nylon mesh, which permits cell migration or invasion from one gel layer to the other. At the end of the assay, the two gel layers are removed from the apparatus and easily separated from each other. Invading cells from the primary gel are trapped in the secondary gel, which maintains the morphology and other properties of the invasive cells in a 3D matrix. The cells that have invaded are observed and counted with a standard light microscope without cell staining. There is no need for a specialized microscope, imaging analysis software, or advanced cell‐biological technical knowledge in this assay. This assay can also reduce measurement of nonspecific cell invasion by monitoring the upward invasion of cells. The viability of both invading and non‐invading cells trapped in the gels can be assessed by typical colorimetric assays, if desired. This assessment characterizes the total number of cells (invading and non‐invading cells) and the ratio of invading cells to total cells. By repeating the iCT assay, further enrichment of invasive and noninvasive cells can be attained. Thus, this assay improves comparative analyses between invasive and noninvasive cells. © 2020 by John Wiley & Sons, Inc.Basic Protocol 1: Measuring upward cell invasion into collagen gelBasic Protocol 2: Measuring cell invasion from Matrigel into collagen gelBasic Protocol 3: Isolation and enrichment of highly invasive cells
Risk of Opioid Overdose Associated With Concomitant Use of Opioids and Skeletal Muscle Relaxants: A Population‐Based Cohort Study
Authors: Li Yan , Delcher Chris , Wei Yu‐Jung Jenny , Reisfield Gary M. , Brown Joshua D. , Tighe Patrick , Winterstein Almut G. 
Published: February 2020

The recent opioid prescribing guideline cautions about the concomitant prescribing of opioids and skeletal muscle relaxants (SMRs) given the additive central nervous system depressant effect. However, the clinical relevance remains unclear. In this retrospective cohort study, we compared the risk of opioid overdose associated with concomitant use of opioids and SMRs vs. opioid use alone. Adjusted hazard ratios were 1.09 (95% confidence interval (CI), 0.74–1.62) and 1.26 (95% CI, 1.00–1.58) in the incident and prevalent opioid user cohorts, respectively, generating a combined estimate of 1.21 (95% CI, 1.00–1.48). This risk seemed to increase with treatment duration (≤ 14 days: 0.91 and 95% CI, 0.67–1.22; 15–60 days: 1.37 and 95% CI, 0.81–2.37; >60 days: 1.80 and 95% CI, 1.30–2.48) and for baclofen (1.83 and 95% CI, 1.11–3.04) and carisoprodol (1.84 and 95% CI, 1.34–2.54). Concomitant users with daily opioid dose ≥50 mg (1.50 and 95% CI, 1.18–1.92) and benzodiazepine use (1.39 and 95% CI, 1.08–1.79) also had elevated risk. Clinicians should be cautious about these potentially unsafe practices to optimize pain care and improve patient safety.
Recovery Behavior of the Luminescence Peak from Graphitic Carbon Nitride as a Function of the Synthesis Temperature
Authors: Chubenko Eugene B. , Denisov Nikita M. , Baglov Aleksey V. , Bondarenko Vitaly P. , Uglov Vladimir V. , Borisenko Viktor E. 
Published: February 2020

AbstractGraphitic carbon nitride (g‐C3N4) is synthesized by thermal decomposition of thiourea and subsequent in situ polymerization of the products in the oxygen‐containing ambient at 450–625 °C and studied with scanning electron microscopy, X‐ray diffraction, energy‐dispersive X‐ray spectroscopy, Fourier‐transform infrared spectroscopy, and photoluminescence techniques. The synthesized material contains oxygen at a concentration increasing with the processing temperature from 4.8 to 9.8 at %. The photoluminescence peak is found to be red‐shifted with the temperature increased to 575 °C becoming then blue‐shifted at higher temperatures. The observed red‐shift of the photoluminescence peak is supposed to be caused by band‐gap narrowing in g‐C3N4 doped by oxygen while its recovery behavior is controlled by thermally induced oxygen‐assisted disruption of sp2 bonds in C‐N π‐orbital conjugated system of tri‐s‐triazine units building polymer sheets in g‐C3N4.
A High‐Power Aqueous Zinc–Organic Radical Battery with Tunable Operating Voltage Triggered by Selected Anions
Authors: Luo Yuwen , Zheng Feipeng , Liu Luojia , Lei Kaixiang , Hou Xuesen , Xu Gang , Meng Hui , Shi Jifu , Li Fujun 
Published: February 2020

AbstractIn contrast to traditional rechargeable rock‐chair metal‐ion batteries, dual‐ion batteries (DIBs) involve redox reactions with anions rather than cations in p‐type cathodes. In principle, regulating the electrochemical performance of the DIB by different anion species is highly feasible. Herein, the anion effect on the electrochemical performance of a DIB, the aqueous Zn– organic radical battery (Zn‐ORB), consisting of a poly(2,2,6,6tetramethylpiperidinyloxy‐4‐yl vinyl ether) cathode and a Zn anode, was investigated by DFT calculations. SO42−, CF3SO3−, and ClO4− with different molecular electrostatic potential values were selected as anion models. DFT calculations revealed that a stronger electrostatic interaction of the anion with the organic radical resulted in a higher operating voltage of the Zn‐ORB, which was consistent with experimental results. These results bring new insight into the redox chemistry of p‐type organic radicals with anions and will promote the development of high‐power aqueous Zn‐ORBs as well as inspire more investigations into the anion effect towards novel battery designs.
Linear distribution of capacitance in Dickson charge pumps to reduce rise time
Authors: Ballo Andrea , Grasso Alfio Dario , Palumbo Gaetano , Tanzawa Toru 
Published: February 2020

SummaryThis paper introduces a design strategy to reduce rise time of charge pumps maintaining equal the silicon area, which is effective when the load capacitance is lower than the total charge pump capacitance. The strategy relies on an unconventional pumping capacitors sizing, which set them not equal and follows a linear distribution. The approach is based on a theoretical analysis and is validated through post‐layout simulations using a 130‐nm complementary metal‐oxide semiconductor (CMOS) standard technology. The simulations demonstrate the advantages of the proposed design strategy and the accuracy of the theory.
A subtree‐based transformation model for cryptosystem using chaotic maps under cloud computing environment for fuzzy user data sharing
Authors: Meshram Chandrashekhar , Lee Cheng‐Chi , Ranadive Abhay S. , Li Chun‐Ta , Meshram Sarita Gajbhiye , Tembhurne Jitendra V. 
Published: February 2020

SummaryCloud computing technologies have been prospering in recent years and have opened an avenue for a wide variety of forms of adaptable data sharing. Taking advantage of these state‐of‐the‐art innovations, the cloud storage data owner must, however, use a suitable identity‐based cryptographic mechanism to ensure the safety prerequisites while sharing data to large numbers of cloud data users with fuzzy identities. As a successful way to guarantee secure fuzzy sharing of cloud data, the identity‐based cryptographic technology still faces an effectiveness problem under multireceiver configurations. The chaos theory is considered a reasonable strategy for reducing computational complexity while meeting the cryptographic protocol's security needs. In an identity‐based cryptographic protocol, public keys for individual clients are distributed, allowing the clients to separately select their own network identities or names as their public keys. In fact, in a public‐key cryptographic protocol, it is for the best that the confirmation of the public key is done in a safe, private manner, because this way the load of storage on the server's side can be considerably relieved. The objective of this paper is to outline and examine a conversion process that can transfer cryptosystems using Chebyshev's chaotic maps over the Galois field to a subtree‐based protocol in the cloud computing setting for fuzzy user data sharing, as opposed to reconcocting a different structure. Furthermore, in the design of our conversion process, no adjustment of the original cryptosystem based on chaotic maps is needed.
Insulin resistance and impaired lipid metabolism as a potential link between diabetes and Alzheimer's disease
Authors: Kulas Joshua A. , Weigel Thaddeus K. , Ferris Heather A. 
Published: February 2020

AbstractDiabetes disrupts organs throughout the body including the brain. Evidence suggests diabetes is a risk factor for Alzheimer's disease (AD) and neurodegeneration. In this review, we focus on understanding how diabetes contributes to the progression of neurodegeneration by influencing several aspects of the disease process. We emphasize the potential roles of brain insulin resistance, as well as cholesterol and lipid disruption, as factors which worsen AD.
Investigating changes in estuarine ecosystem functioning under future scenarios
Authors: Hillman Jenny R. , Stephenson Fabrice , Thrush Simon F. , Lundquist Carolyn J. 
Published: February 2020

AbstractEstuaries are subject to disturbance by land‐based sediment and nutrient inputs, resulting in changes to the ecosystems and the functions and services that they support. Spatial mapping tools that identify how functional hotspots in the estuary may shift in location and intensity under different disturbance scenarios highlight to managers the trajectory of change and the value of active management and restoration, but to date these tools are only available in the most intensively researched ecosystems. Using empirical data derived from long‐term monitoring and multi‐habitat field experiments we developed future scenarios representing different impacts of environmental degradation on estuarine ecosystem functions that are important for supporting ecosystem services. We used the spatial prioritization software Zonation in a novel fashion to assess effects of different disturbance scenarios on critical soft‐sediment ecosystem processes (nutrient fluxes and sediment erodibility measures) that are influenced by macrofaunal communities and local environment conditions. We compared estimates of current conditions with three scenarios linked to changes in land‐use and resulting downstream impacts on estuarine ecosystems to determine how disturbance influences the distribution of high value areas for ecosystem function. Scenarios investigated the implications of habitat degradation associated with sediment deposition and declines in large sediment‐dwelling animal abundance whose behavior has important influences on ecosystem function. Our analyses demonstrate decreases in the majority of ecosystem processes under scenarios associated with disturbances. These results suggest that it is important to restore biodiversity and ecosystem function and that the application of Zonation in this context offers a simple, rapid and cost‐effective way of identifying priority actions and locations for restoration, and how these shift due to multiple impacts.
Genomic signatures of host‐associated divergence and adaptation in a coral‐eating snail, Coralliophila violacea (Kiener, 1836)
Authors: Simmonds Sara E. , Fritts‐Penniman Allison L. , Cheng Samantha H. , Mahardika Gusti Ngurah , Barber Paul H. 
Published: February 2020

AbstractThe fluid nature of the ocean, combined with planktonic dispersal of marine larvae, lowers physical barriers to gene flow. However, divergence can still occur despite gene flow if strong selection acts on populations occupying different ecological niches. Here, we examined the population genomics of an ectoparasitic snail, Coralliophila violacea (Kiener 1836), that specializes on Porites corals in the Indo‐Pacific. Previous genetic analyses revealed two sympatric lineages associated with different coral hosts. In this study, we examined the mechanisms promoting and maintaining the snails’ adaptation to their coral hosts. Genome‐wide single nucleotide polymorphism (SNP) data from type II restriction site‐associated DNA (2b‐RAD) sequencing revealed two differentiated clusters of C. violacea that were largely concordant with coral host, consistent with previous genetic results. However, the presence of some admixed genotypes indicates gene flow from one lineage to the other. Combined, these results suggest that differentiation between host‐associated lineages of C. violacea is occurring in the face of ongoing gene flow, requiring strong selection. Indeed, 2.7% of all SNP loci were outlier loci (73/2,718), indicative of divergence with gene flow, driven by adaptation of each C. violacea lineage to their specific coral hosts.
Remotely sensed forest understory density and nest predator occurrence interact to predict suitable breeding habitat and the occurrence of a resident boreal bird species
Authors: Klein Julian , Haverkamp Paul J. , Lindberg Eva , Griesser Michael , Eggers Sönke 
Published: February 2020

AbstractHabitat suitability models (HSM) based on remotely sensed data are useful tools in conservation work. However, they typically use species occurrence data rather than robust demographic variables, and their predictive power is rarely evaluated. These shortcomings can result in misleading guidance for conservation. Here, we develop and evaluate a HSM based on correlates of long‐term breeding success of an open nest building boreal forest bird, the Siberian jay. In our study site in northern Sweden, nest failure of this permanent resident species is driven mainly by visually hunting corvids that are associated with human settlements. Parents rely on understory nesting cover as protection against these predators. Accordingly, our HSM includes a light detection and ranging (LiDAR) based metric of understory density around the nest and the distance of the nest to the closest human settlement to predict breeding success. It reveals that a high understory density 15–80 m around nests is associated with increased breeding success in territories close to settlements (<1.5 km). Farther away from human settlements breeding success is highest at nest sites with a more open understory providing a favorable warmer microclimate. We validated this HSM by comparing the predicted breeding success with landscape‐wide census data on Siberian jay occurrence. The correlation between breeding success and occurrence was strong up to 40 km around the study site. However, the HSM appears to overestimate breeding success in regions with a milder climate and therefore higher corvid numbers. Our findings suggest that maintaining patches of small diameter trees may provide a cost‐effective way to restore the breeding habitat for Siberian jays up to 1.5 km from human settlements. This distance is expected to increase in the warmer, southern, and coastal range of the Siberian jay where the presence of other corvids is to a lesser extent restricted to settlements.