bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a juvenile-hormone signaling inhibitor via high-throughput screening of a chemical library
Authors: Kayukawa Takumi , Furuta Kenjiro , Nagamine Keisuke , Shinoda Tetsuro , Yonesu Kiyoaki , Okabe Takayoshi 
Published: October 2020

AbstractInsecticide resistance has recently become a serious problem in the agricultural field. Development of insecticides with new mechanisms of action is essential to overcome this limitation. Juvenile hormone (JH) is an insect-specific hormone that plays key roles in maintaining the larval stage of insects. Hence, JH signaling pathway is considered a suitable target in the development of novel insecticides; however, only a few JH signaling inhibitors (JHSIs) have been reported, and no practical JHSIs have been developed. Here, we established a high-throughput screening (HTS) system for exploration of novel JHSIs using a Bombyx mori cell line (BmN_JF&AR cells) and carried out a large-scale screening in this cell line using a chemical library. The four-step HTS yielded 69 compounds as candidate JHSIs. Topical application of JHSI48 to B. mori larvae caused precocious metamorphosis. In ex vivo culture of the epidermis, JHSI48 suppressed the expression of the Krüppel homolog 1 gene, which is directly activated by JH-liganded receptor. Moreover, JHSI48 caused a parallel rightward shift in the JH response curve, suggesting that JHSI48 possesses a competitive antagonist-like activity. Thus, large-scale HTS using chemical libraries may have applications in development of future insecticides targeting the JH signaling pathway.
NSAIDs-dependent adaption of the mitochondria-proteasome system in immortalized human cardiomyocytes
Authors: Brandolini Laura , Antonosante Andrea , Giorgio Cristina , Bagnasco Michela , d’Angelo Michele , Castelli Vanessa , Benedetti Elisabetta , Cimini Annamaria , Allegretti Marcello 
Published: October 2020

AbstractThe progressive consumption growth of non-steroidal anti-inflammatory drugs (NSAIDs) has progressively raised the attention toward the gastrointestinal, renal, and cardiovascular toxicity. Increased risk of cardiovascular diseases was strictly associated with the usage of COX-2 selective NSAIDs. Other studies allowed to clarify that the cardiovascular risk is not limited to COX-2 selective but also extended to non-selective NSAIDs, such as Diclofenac and Ketoprofen. To date, although a less favorable cardiovascular risk profile for Diclofenac as compared to Ketoprofen is reported, the mechanisms through which NSAIDs cause adverse cardiovascular events are not entirely understood. The present study aimed to evaluate the effects of Ketoprofen in comparison with Diclofenac in immortalized human cardiomyocytes. The results obtained highlight the dose-dependent cardiotoxicity of Diclofenac compared to Ketoprofen. Despite both drugs induce the increase in ROS production, decrease of mitochondrial membrane potential, and proteasome activity modulation, only Diclofenac exposure shows a marked alteration of these intracellular parameters, leading to cell death. Noteworthy, Diclofenac decreases the proteasome 26S DC and this scenario may be dependent on the intracellular overload of oxidized proteins. The data support the hypothesis that immortalized human cardiomyocytes exposed to Ketoprofen are subjected to tolerable stress events, conversely Diclofenac exposition triggers cell death.
pHLIP ICG for delineation of tumors and blood flow during fluorescence-guided surgery
Authors: Crawford Troy , Moshnikova Anna , Roles Sean , Weerakkody Dhammika , DuPont Michael , Carter Lukas M. , Shen John , Engelman Donald M. , Lewis Jason S. , Andreev Oleg A. , Reshetnyak Yana K. 
Published: October 2020

AbstractFluorescence imaging has seen enduring use in blood flow visualization and is now finding a new range of applications in image-guided surgery. In this paper, we report a translational study of a new fluorescent agent for use in surgery, pHLIP ICG, where ICG (indocyanine green) is a surgical fluorescent dye used widely for imaging blood flow. We studied pHLIP ICG interaction with the cell membrane lipid bilayer, the pharmacology and toxicology in vitro and in vivo (mice and dogs), and the biodistribution and clearance of pHLIP ICG in mice. The pHLIP ICG tumor targeting and imaging efficacy studies were carried out in several murine and human mouse tumor models. Blood vessels were imaged in mice and pigs. Clinical Stryker imaging instruments for endoscopy and open surgery were used in the study. Intravenously administered pHLIP ICG exhibits a multi-hour circulation half-life, offering protracted delineation of vasculature. As it clears from the blood, pHLIP ICG targets tumors and tumor stroma, marking them for surgical removal. pHLIP ICG is non-toxic, marks blood flow for hours after injection, and effectively delineates tumors for improved resection on the day after administration.
Identification of methionine -rich insoluble proteins in the shell of the pearl oyster, Pinctada fucata
Authors: Kintsu Hiroyuki , Nishimura Ryo , Negishi Lumi , Kuriyama Isao , Tsuchihashi Yasushi , Zhu Lingxiao , Nagata Koji , Suzuki Michio 
Published: October 2020

AbstractThe molluscan shell is a biomineral that comprises calcium carbonate and organic matrices controlling the crystal growth of calcium carbonate. The main components of organic matrices are insoluble chitin and proteins. Various kinds of proteins have been identified by solubilizing them with reagents, such as acid or detergent. However, insoluble proteins remained due to the formation of a solid complex with chitin. Herein, we identified these proteins from the nacreous layer, prismatic layer, and hinge ligament of Pinctada fucata using mercaptoethanol and trypsin. Most identified proteins contained a methionine-rich region in common. We focused on one of these proteins, NU-5, to examine the function in shell formation. Gene expression analysis of NU-5 showed that NU-5 was highly expressed in the mantle, and a knockdown of NU-5 prevented the formation of aragonite tablets in the nacre, which suggested that NU-5 was required for nacre formation. Dynamic light scattering and circular dichroism revealed that recombinant NU-5 had aggregation activity and changed its secondary structure in the presence of calcium ions. These findings suggest that insoluble proteins containing methionine-rich regions may be important for scaffold formation, which is an initial stage of biomineral formation.
Resolving the data asynchronicity in high-speed atomic force microscopy measurement via the Kalman Smoother
Authors: Kubo Shintaroh , Kato Suguru , Nakamura Kazuyuki , Kodera Noriyuki , Takada Shoji 
Published: October 2020

AbstractHigh-speed atomic force microscopy (HS-AFM) is a scanning probe microscopy that can capture structural dynamics of biomolecules in real time at single molecule level near physiological condition. Albeit much improvement, while scanning one frame of HS-AFM movies, biomolecules often change their conformations largely. Thus, the obtained frame images can be hampered by the time-difference, the asynchronicity, in the data acquisition. Here, to resolve this data asynchronicity in the HS-AFM movie, we developed Kalman filter and smoother methods, some of the sequential Bayesian filtering approaches. The Kalman filter/smoother methods use alternative steps of a short time-propagation by a linear dynamical system and a correction by the likelihood of AFM data acquired pixel by pixel. We first tested the method using a toy model of a diffusing cone, showing that the Kalman smoother method outperforms to reproduce the ground-truth movie. We then applied the Kalman smoother to a synthetic movie for conformational change dynamics of a motor protein, i.e., dynein, confirming the superiority of the Kalman smoother. Finally, we applied the Kalman smoother to two real HS-AFM movies, FlhAC and centralspindlin, reducing distortion and noise in the AFM movies. The method is general and can be applied to any HS-AFM movies.
Biomechanical effects of original equipment manufacturer and aftermarket abutment screws in zirconia abutment on dental implant assembly
Authors: Wu Yu-Ling , Tsai Ming-Hsu , Chen Hung-Shyong , Chang Yu-Tsen , Lin Tsai-Te , Wu Aaron Yu-Jen 
Published: October 2020

AbstractThe use of aftermarket computer-aided design/computer-assisted manufacturing (CAD/CAM) prosthesis components in dental implants has become popular. This study aimed to (1) compare the accuracy of aftermarket CAD/CAM screws with that of original equipment manufacturer (OEM) abutment screws and (2) examine the biomechanical effects of different abutment screws used with zirconia abutment in an implant fixture by using three-dimensional finite element analysis (FEA). Significantly different measurements were obtained for the aftermarket CAD/CAM and OEM screws. The FEA results indicated that under the same loading condition, the maximum stress of the aftermarket CAD/CAM screws was 15.9% higher than that of the OEM screws. Moreover, the maximum stress position occurred in a wide section of the OEM screws but in the narrowest section of the aftermarket screws. The stress of the OEM zirconia abutment was 14.9% higher when using the aftermarket screws than when using the OEM screws. The effect of the manufacturing differences between aftermarket and OEM screws on the clinical effect of aftermarket screws is unpredictable. Therefore, aftermarket screws should be cautiously used clinically.
Protection against SARS-CoV-2 by BCG vaccination is not supported by epidemiological analyses
Authors: Hensel Janine , McAndrews Kathleen M. , McGrail Daniel J. , Dowlatshahi Dara P. , LeBleu Valerie S. , Kalluri Raghu 
Published: October 2020

AbstractThe Bacillus Calmette–Guerin (BCG) vaccine provides protection against tuberculosis (TB), and is thought to provide protection against non-TB infectious diseases. BCG vaccination has recently been proposed as a strategy to prevent infection with SARS-CoV-2 (CoV-2) to combat the COVID-19 outbreak, supported by its potential to boost innate immunity and initial epidemiological analyses which observed reduced severity of COVID-19 in countries with universal BCG vaccination policies. Seventeen clinical trials are currently registered to inform on the benefits of BCG vaccinations upon exposure to CoV-2. Numerous epidemiological analyses showed a correlation between incidence of COVID-19 and BCG vaccination policies. These studies were not systematically corrected for confounding variables. We observed that after correction for confounding variables, most notably testing rates, there was no association between BCG vaccination policy and COVD-19 spread rate or percent mortality. Moreover, we found variables describing co-morbidities, including cardiovascular death rate and smoking prevalence, were significantly associated COVID-19 spread rate and percent mortality, respectively. While reporting biases may confound our observations, our epidemiological findings do not provide evidence to correlate overall BCG vaccination policy with the spread of CoV-2 and its associated mortality.
Analysis of streaming potential flow and electroviscous effect in a shear-driven charged slit microchannel
Authors: Riad Adham , Khorshidi Behnam , Sadrzadeh Mohtada 
Published: October 2020

AbstractInvestigating the flow behavior in microfluidic systems has become of interest due to the need for precise control of the mass and momentum transport in microfluidic devices. In multilayered-flows, precise control of the flow behavior requires a more thorough understanding as it depends on multiple parameters. The following paper proposes a microfluidic system consisting of an aqueous solution between a moving plate and a stationary wall, where the moving plate mimics a charged oil–water interface. Analytical expressions are derived by solving the nonlinear Poisson–Boltzmann equation along with the simplified Navier–Stokes equation to describe the electrokinetic effects on the shear-driven flow of the aqueous electrolyte solution. The Debye–Huckel approximation is not employed in the derivation extending its compatibility to high interfacial zeta potential. Additionally, a numerical model is developed to predict the streaming potential flow created due to the shear-driven motion of the charged upper wall along with its associated electric double layer effect. The model utilizes the extended Nernst–Planck equations instead of the linearized Poisson–Boltzmann equation to accurately predict the axial variation in ion concentration along the microchannel. Results show that the interfacial zeta potential of the moving interface greatly impacts the velocity profile of the flow and can reverse its overall direction. The numerical results are validated by the analytical expressions, where both models predicted that flow could reverse its overall direction when the interfacial zeta potential of the oil–water is above a certain threshold value. Finally, this paper describes the electroviscous effect as well as the transient development of electrokinetic effects within the microchannel.
A pilot clinical study of the therapeutic antibody against canine PD-1 for advanced spontaneous cancers in dogs
Authors: Igase Masaya , Nemoto Yuki , Itamoto Kazuhito , Tani Kenji , Nakaichi Munekazu , Sakurai Masashi , Sakai Yusuke , Noguchi Shunsuke , Kato Masahiro , Tsukui Toshihiro , Mizuno Takuya 
Published: October 2020

AbstractInhibition of programmed death 1 (PD-1), expressed on activated T cells, can break through immune resistance and elicit durable responses in human melanoma as well as other types of cancers. Canine oral malignant melanoma is one of the most aggressive tumors bearing poor prognosis due to its high metastatic potency. However, there are few effective treatments for the advanced stages of melanoma in veterinary medicine. Only one previous study indicated the potential of the immune checkpoint inhibitor, anti-canine PD-L1 therapeutic antibody in dogs, and no anti-canine PD-1 therapeutic antibodies are currently available. Here, we developed two therapeutic antibodies, rat-dog chimeric and caninized anti-canine PD-1 monoclonal antibodies and evaluated in vitro functionality for these antibodies. Moreover, we conducted a pilot study to determine their safety profiles and clinical efficacy in spontaneously occurring canine cancers. In conclusion, the anti-canine PD-1 monoclonal antibody was relatively safe and effective in dogs with advanced oral malignant melanoma and other cancers. Thus, our study suggests that PD-1 blockade may be an attractive treatment option in canine cancers.
Development of a novel immune-related genes prognostic signature for osteosarcoma
Authors: Wu Zuo-long , Deng Ya-jun , Zhang Guang-zhi , Ren En-hui , Yuan Wen-hua , Xie Qi-qi 
Published: October 2020

AbstractImmune-related genes (IRGs) are responsible for osteosarcoma (OS) initiation and development. We aimed to develop an optimal IRGs-based signature to assess of OS prognosis. Sample gene expression profiles and clinical information were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Genotype-Tissue Expression (GTEx) databases. IRGs were obtained from the ImmPort database. R software was used to screen differentially expressed IRGs (DEIRGs) and functional correlation analysis. DEIRGs were analyzed by univariate Cox regression and iterative LASSO Cox regression analysis to develop an optimal prognostic signature, and the signature was further verified by independent cohort (GSE39055) and clinical correlation analysis. The analyses yielded 604 DEIRGs and 10 hub IRGs. A prognostic signature consisting of 13 IRGs was constructed, which strikingly correlated with OS overall survival and distant metastasis (p < 0.05, p < 0.01), and clinical subgroup showed that the signature’s prognostic ability was independent of clinicopathological factors. Univariate and multivariate Cox regression analyses also supported its prognostic value. In conclusion, we developed an IRGs signature that is a prognostic indicator in OS patients, and the signature might serve as potential prognostic indicator to identify outcome of OS and facilitate personalized management of the high-risk patients.
Transferrin receptor 1 is a cellular receptor for human heme-albumin
Authors: Jennifer Brell , Berg Verena , Modak Madhura , Puck Alexander , Seyerl-Jiresch Maria , Künig Sarojinidevi , Zlabinger Gerhard J. , Steinberger Peter , Chou Janet , Geha Raif S. , Öhler Leopold , Yachie Akihiro , Choe Hyeryun , Kraller Markus , Stockinger Hannes , Stöckl Johannes 
Published: October 2020

AbstractIron is essential for living cells. Uptake of iron-loaded transferrin by the transferrin receptor 1 (CD71, TFR) is a major but not sufficient mechanism and an alternative iron-loaded ligand for CD71 has been assumed. Here, we demonstrate that CD71 utilizes heme-albumin as cargo to transport iron into human cells. Binding and endocytosis of heme-albumin via CD71 was sufficient to promote proliferation of various cell types in the absence of transferrin. Growth and differentiation of cells induced by heme-albumin was dependent on heme-oxygenase 1 (HO-1) function and was accompanied with an increase of the intracellular labile iron pool (LIP). Import of heme-albumin via CD71 was further found to contribute to the efficacy of albumin-based drugs such as the chemotherapeutic Abraxane. Thus, heme-albumin/CD71 interaction is a novel route to transport nutrients or drugs into cells and adds to the emerging function of CD71 as a scavenger receptor.
Lysosomal trafficking mediated by Arl8b and BORC promotes invasion of cancer cells that survive radiation
Authors: Wu Ping-Hsiu , Onodera Yasuhito , Giaccia Amato J. , Le Quynh-Thu , Shimizu Shinichi , Shirato Hiroki , Nam Jin-Min 
Published: October 2020

AbstractEnhanced invasiveness, a critical determinant of metastasis and poor prognosis, has been observed in cancer cells that survive cancer therapy, including radiotherapy. Here, we show that invasiveness in radiation-surviving cancer cells is associated with alterations in lysosomal exocytosis caused by the enhanced activation of Arl8b, a small GTPase that regulates lysosomal trafficking. The binding of Arl8b with its effector, SKIP, is increased after radiation through regulation of BORC-subunits. Knockdown of Arl8b or BORC-subunits decreases lysosomal exocytosis and the invasiveness of radiation-surviving cells. Notably, high expression ofARL8Band BORC-subunit genes is significantly correlated with poor prognosis in breast cancer patients. Sp1, an ATM-regulated transcription factor, is found to increase BORC-subunit genes expression after radiation. In vivo experiments show that ablation of Arl8b decreases IR-induced invasive tumor growth and distant metastasis. These findings suggest that BORC-Arl8b-mediated lysosomal trafficking is a target for improving radiotherapy by inhibiting invasive tumor growth and metastasis.
Coulomb drag transistor using a graphene and MoS2 heterostructure
Authors: Jin Youngjo , Joo Min-Kyu , Moon Byoung Hee , Kim Hyun , Lee Sanghyup , Jeong Hye Yun , Lee Young Hee 
Published: October 2020

AbstractTwo-dimensional (2D) heterostructures often provide extraordinary carrier transport as exemplified by superconductivity or excitonic superfluidity. Recently, a double-layer graphene (Gr) separated by few-layered boron nitride demonstrated the Coulomb drag phenomenon: carriers in the active layer drag carriers in the passive layer. Here, we propose high-performance Gr/MoS2 heterostructure transistors operating via Coulomb drag, exhibiting a high carrier mobility (∼3700 cm2 V−1 s−1) and on/off-current ratio (∼108) at room temperature. The van der Waals gap at the Gr/MoS2 interface induces strong interactions between the interlayer carriers, whose recombination is suppressed by the Schottky barrier between p-Gr and n-MoS2, clearly distinct from the presence of insulating layers. The sign reversal of lateral voltage clearly demonstrates the Coulomb drag in carrier transport. Hole-like behavior of electrons in the n-MoS2 is observed in magnetic field, indicating strong Coulomb drag at low temperature. Our Coulomb drag transistor thus provides a shortcut for the practical application of 2D heterostructures.
Survey of Hearing Health During the COVID-19 Pandemic: Implications for Service Delivery
Authors: Gaeta Laura 
Published: October 2020

Purpose
This study aimed to explore older adults' perceptions of their hearing health during the stay-at-home order issued during the COVID-19 pandemic.

Method
A 24-item survey was completed by 150 community-dwelling older adults in the United States. Participants were asked about their self-reported hearing status, use of hearing aids and difficulty wearing masks while wearing hearing aids, relative importance of their hearing health, priority of their hearing health during the COVID-19 pandemic, difficulty communicating with masks, and utilization of telepractice services.

Results
The majority of participants did not wear hearing aids despite reporting that they had at least a little trouble hearing. Most participants reported that their hearing health was important and indicated that they were likely to visit their audiologist for an in-person or virtual visit during the pandemic.

Conclusion
Audiologists should consider telepractice or remote service delivery options during and after the COVID-19 pandemic to meet the needs of their patients.
Oscillations of 2D ESTER models
Authors: Reese D. R. , Mirouh G. M. , Espinosa Lara F. , Rieutord M. , Putigny B. 
Published: October 2020

Context.Recent numerical and theoretical considerations have shown that low-degree acoustic modes in rapidly rotating stars follow an asymptotic formula. In parallel, recent studies have revealed the presence of regular pulsation frequency patterns in rapidly rotatingδScuti stars that seem to match theoretical expectations.Aims.In this context, a key question is whether strong gradients or discontinuities can adversely affect the asymptotic frequency pattern to the point of hindering its identification. Other important questions are how rotational splittings are affected by the 2D rotation profiles expected from baroclinic effects and whether it is possible to probe the rotation profile using these splittings.Methods.In order to address these questions, we numerically calculate stellar pulsation modes in continuous and discontinuous rapidly rotating models produced by the 2D Evolution STEllaire en Rotation (ESTER) code. This code self-consistently calculates the rotation profile based on baroclinic effects and uses a spectral multi-domain approach, thus making it possible to introduce discontinuities at the domain interfaces without loss of numerical accuracy. The pulsation calculations are carried out using an adiabatic version of the Two-dimensional Oscillation Program (TOP) code. The variational principle is then used to confirm the high numerical accuracy of the pulsation frequencies and to derive an integral formula for the generalised rotational splittings. Acoustic glitch theory, combined with ray dynamics, is applied to the discontinuous models in order to interpret their pulsation spectra.Results.Our results show that the generalised rotational splittings are very well approximated by the integral formula, except for modes involved in avoided crossings. This potentially allows the application of inverse theory for probing the rotation profile. We also show that glitch theory applied along the island mode orbit can correctly predict the periodicity of the glitch frequency pattern produced by the discontinuity or Γ1dip related to the He II ionisation zone in some of the models. Furthermore, the asymptotic frequency pattern remains sufficiently well preserved to potentially allow its detection in observed stars.