bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperthermia depletes Oct4 in mouse blastocysts and stem cells
Authors: Cheng Mo-bin , Wang Xue , Huang Yue , Zhang Ye 
Published: May 2020

AbstractTemperature is an important microenvironmental factor that functions epigenetically in normal embryonic development. However, the effect of hyperthermia in the stem cells is not fully understood. Oct4 is a tightly regulated master regulator of pluripotency maintenance in stem cells and during early embryonic development. We report here that Oct4 protein level was significantly reduced under hyperthermia in mouse blastocysts and embryonic stem cells. The reduction in Oct4 in the mouse embryonic stem cells under hyperthermia was mediated by a ubiquitin-proteasome pathway that was dependent on the activity of death-associated protein kinase 1 (Dapk1) to phosphorylate its substrate, Pin1. Our results imply that the depletion of Oct4 via brief hyperthermia, such as a high fever, during early pregnancy might severely impair the growth of the mammalian embryo or even cause its death.
Assessing the information content of structural and protein–ligand interaction representations for the classification of kinase inhibitor binding modes via machine learning and active learning
Authors: Rodríguez-Pérez Raquel , Miljković Filip , Bajorath Jürgen 
Published: May 2020

AbstractFor kinase inhibitors, X-ray crystallography has revealed different types of binding modes. Currently, more than 2000 kinase inhibitors with known binding modes are available, which makes it possible to derive and test machine learning models for the prediction of inhibitors with different binding modes. We have addressed this prediction task to evaluate and compare the information content of distinct molecular representations including protein–ligand interaction fingerprints (IFPs) and compound structure-based structural fingerprints (i.e., atom environment/fragment fingerprints). IFPs were designed to capture binding mode-specific interaction patterns at different resolution levels. Accurate predictions of kinase inhibitor binding modes were achieved with random forests using both representations. The performance of IFPs was consistently superior to atom environment fingerprints, albeit only by less than 10%. An active learning strategy applying information entropy-based selection of training instances was applied as a diagnostic approach to assess the relative information content of distinct representations. IFPs were found to capture more binding mode-relevant information than atom environment fingerprints, leading to highly predictive models even when training instances were randomly selected. By contrast, for atom environment fingerprints, the derivation of accurate models via active learning depended on entropy-based selection of informative training compounds. Notably, higher information content of IFPs confirmed by active learning only resulted in small improvements in global prediction accuracy compared to models derived using atom environment fingerprints. For practical applications, prediction of binding modes of new kinase inhibitors on the basis of chemical structure is highly attractive.
Comparison of diagnostic sensitivity of [18F]fluoroestradiol and [18F]fluorodeoxyglucose positron emission tomography/computed tomography for breast cancer recurrence in patients with a history of estrogen receptor-positive primary breast cancer
Authors: Chae Sun Young , Son Hye Joo , Lee Dong Yun , Shin Eonwoo , Oh Jungsu S. , Seo Seung Yeon , Baek Sora , Kim Ji Young , Na Sae Jung , Moon Dae Hyuk 
Published: May 2020

Abstract
Background
To compare the diagnostic sensitivity of [18F]fluoroestradiol ([18F]FES) and [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) for breast cancer recurrence in patients with estrogen receptor (ER)-positive primary breast cancer.

Methods
Our database of consecutive patients enrolled in a previous prospective cohort study to assess [18F]FES PET/CT was reviewed to identify eligible patients who had ER-positive primary breast cancer with suspected first recurrence at presentation and who underwent [18F]FDG PET/CT. The sensitivity of qualitative [18F]FES and [18F]FDG PET/CT interpretations was assessed, comparing them with histological diagnoses.

Results
Of the 46 enrolled patients, 45 were confirmed as having recurrent breast cancer, while one was diagnosed with chronic granulomatous inflammation. Forty (89%) patients were ER-positive, four (9%) were ER-negative, and one (2%) patient did not undergo an ER assay. The sensitivity of [18F]FES PET/CT was 71.1% (32/45, 95% CI, 55.7–83.6), while that of [18F]FDG PET/CT was 80.0% (36/45, 95% CI, 65.4–90.4) with a threshold of positive interpretation, and 93.3% (42/45, 95% CI, 81.7–98.6) when a threshold of equivocal was used. There was no significant difference in sensitivity between [18F]FES and [18F]FDG PET/CT (P = 0.48) with a threshold of positive [18F]FDG uptake, but the sensitivity of [18F]FDG was significantly higher than [18F]FES (P = 0.013) with a threshold of equivocal [18F]FDG uptake. One patient with a benign lesion showed negative [18F]FES but positive [18F]FDG uptake.

Conclusions
The restaging of patients who had ER-positive primary breast cancer and present with recurrent disease may include [18F]FES PET/CT as an initial test when standard imaging studies are equivocal or suspicious.
Characterization of FsXEG12A from the cellulose-degrading ectosymbiotic fungus Fusarium spp. strain EI cultured by the ambrosia beetle
Authors: Sakai Kiyota , Yamaguchi Aya , Tsutsumi Seitaro , Kawai Yuto , Tsuzuki Sho , Suzuki Hiromitsu , Jindou Sadanari , Suzuki Yoshihito , Kajimura Hisashi , Kato Masashi , Shimizu Motoyuki 
Published: May 2020

AbstractDespite the threat of Fusarium dieback posed due to ambrosia fungi cultured by ambrosia beetles such as Euwallacea spp., the wood-degradation mechanisms utilized by ambrosia fungi are not fully understood. In this study, we analyzed the 16S rRNA and 18S rRNA genes of the microbial community from the Ficus tree tunnel excavated by Euwallacea interjectus and isolated the cellulose-degrading fungus, Fusarium spp. strain EI, by enrichment culture with carboxymethyl cellulose as the sole carbon source. The cellulolytic enzyme secreted by the fungus was identified and expressed in Pichia pastoris, and its enzymatic properties were characterized. The cellulolytic enzyme, termed FsXEG12A, could hydrolyze carboxymethyl cellulose, microcrystalline cellulose, xyloglucan, lichenan, and glucomannan, indicating that the broad substrate specificity of FsXEG12A could be beneficial for degrading complex wood components such as cellulose, xyloglucan, and galactoglucomannan in angiosperms. Inhibition of FsXEG12A function is, thus, an effective target for Fusarium dieback caused by Euwallacea spp.
Metabolic enzyme clustering by coiled coils improves the biosynthesis of resveratrol and mevalonate
Authors: Fink Tina , Stevović Bojana , Verwaal René , Roubos Johannes A. , Gaber Rok , Benčina Mojca , Jerala Roman , Gradišar Helena 
Published: May 2020

AbstractThe clustering of biosynthetic enzymes is used in nature to channel reaction products and increase the yield of compounds produced by multiple reaction steps. The coupling of multiple enzymes has been shown to increase the biosynthetic product yield. Different clustering strategies have particular advantages as the spatial organization of multiple enzymes creates biocatalytic cascades with a higher efficiency of biochemical reaction. However, there are also some drawbacks, such as misfolding and the variable stability of interaction domains, which may differ between particular biosynthetic reactions and the host organism. Here, we compared different protein-based clustering strategies, including direct fusion, fusion mediated by intein, and noncovalent interactions mediated through small coiled-coil dimer-forming domains. The clustering of enzymes through orthogonally designed coiled-coil interaction domains increased the production of resveratrol in Escherichia coli more than the intein-mediated fusion of biosynthetic enzymes. The improvement of resveratrol production correlated with the stability of the coiled-coil dimers. The coiled-coil fusion-based approach also increased mevalonate production in Saccharomyces cerevisiae, thus demonstrating the wider applicability of this strategy.
Emerging functions and clinical applications of exosomes in human oral diseases
Authors: Peng Qiao , Yang Jing-ya , Zhou Gang 
Published: May 2020

AbstractExosomes are cell-derived membranous vesicles of endosomal origin secreted by all type of cells and present in various body fluids. Exosomes are enriched in peptides, lipids, and nucleic acids, emerging as vital modulators in intercellular communication. Exosomes are increasingly being evaluated as biomarkers for diagnosis and prognosis of diseases, because the constituents of exosomes could be reprogrammed depending on the states of diseases. These features also make exosomes a research hotspot in oral diseases in recent years. In this review, we outlined the characteristics of exosomes, focused on the differential expressions and altered biological functions of exosomes in oral diseases, including oral squamous cell carcinoma, oral leukoplakia, periodontitis, primary Sjögren’s syndrome, oral lichen planus, as well as hand foot and mouth disease. Besides, accumulated evidence documents that it is implementable to consider the natural nanostructured exosomes as a new strategy for disease treatment. Herein, we highlighted the therapeutic potential of exosomes in oral tissue regeneration, oncotherapy, wound healing, and their superiority as therapeutic drug delivery vehicles.
Metoprolol alleviates arginine vasopressin-induced cardiomyocyte hypertrophy by upregulating the AKT1–SERCA2 cascade in H9C2 cells
Authors: Zhao Jieqiong , Lei Yonghong , Yang Yanping , Gao Haibo , Gai Zhongchao , Li Xue 
Published: May 2020

Abstract
Background
Arginine vasopressin (AVP) is elevated in patients with heart failure, and the increase in the AVP concentration in plasma is positively correlated with disease severity and mortality. Metoprolol (Met) is a beta blocker that is widely used in the clinic to treat pathological cardiac hypertrophy and to improve heart function. However, the specific mechanism by which Met alleviates AVP-induced pathological cardiac hypertrophy is still unknown. Our current study aimed to evaluate the inhibitory effects of Met on AVP-induced cardiomyocyte hypertrophy and the underlying mechanisms.

Methods
AVP alone or AVP plus Met was added to the wild type or AKT1-overexpressing rat cardiac H9C2 cell line. The cell surface areas and ANP/BNP/β-MHC expressions were used to evaluate the levels of hypertrophy. Western bolting was used to analyze AKT1/P-AKT1, AKT2/P-AKT2, total AKT, SERCA2, and Phospholamban (PLN) expression. Fluo3-AM was used to measure the intracellular Ca2+ stores.

Results
In the current study, we found that AKT1 but not AKT2 mediated the pathogenesis of AVP-induced cardiomyocyte hypertrophy. Sustained stimulation (48 h) with AVP led to hypertrophy in the H9C2 rat cardiomyocytes, resulting in the downregulation of AKT1 (0.48 fold compared to control) and SERCA2 (0.62 fold), the upregulation of PLN (1.32 fold), and the increase in the cytoplasmic calcium concentration (1.52 fold). In addition, AKT1 overexpression increased the expression of SERCA2 (1.34 fold) and decreased the expression of PLN (0.48 fold) in the H9C2 cells. Moreover, we found that Met could attenuate the AVP-induced changes in AKT1, SERCA2 and PLN expression and decreased the cytoplasmic calcium concentration in the H9C2 cells.

Conclusions
Our results demonstrated that the AKT1–SERCA2 cascade served as an important regulatory pathway in AVP-induced pathological cardiac hypertrophy.
Use, timing and factors associated with tracheal intubation in septic shock: a prospective multicentric observational study
Authors: Darreau C. , Martino F. , Saint-Martin M. , Jacquier S. , Hamel J. F. , Nay M. A. , Terzi N. , Ledoux G. , Roche-Campo F. , Camous L. , Pene F. , Balzer T. , Bagate F. , Lorber J. , Bouju P. , Marois C. , Robert R. , Gaudry S. , Commereuc M. , Debarre M. , Chudeau N. , Labroca P. , Merouani K. , Egreteau P. Y. , Peigne V. , Bornstain C. , Lebas E. , Benezit F. , Vally S. , Lasocki S. , Robert A. , Delbove A. , Lerolle N. 
Published: May 2020

Abstract
Background
No recommendation exists about the timing and setting for tracheal intubation and mechanical ventilation in septic shock.

Patients and methods
This prospective multicenter observational study was conducted in 30 ICUs in France and Spain. All consecutive patients presenting with septic shock were eligible. The use of tracheal intubation was described across the participating ICUs. A multivariate analysis was performed to identify parameters associated with early intubation (before H8 following vasopressor onset).

Results
Eight hundred and fifty-nine patients were enrolled. Two hundred and nine patients were intubated early (24%, range 4.5–47%), across the 18 centers with at least 20 patients included. The cumulative intubation rate during the ICU stay was 324/859 (38%, range 14–65%). In the multivariate analysis, seven parameters were significantly associated with early intubation and ranked as follows by decreasing weight: Glasgow score, center effect, use of accessory respiratory muscles, lactate level, vasopressor dose, pH and inability to clear tracheal secretions. Global R-square of the model was only 60% indicating that 40% of the variability of the intubation process was related to other parameters than those entered in this analysis.

Conclusion
Neurological, respiratory and hemodynamic parameters only partially explained the use of tracheal intubation in septic shock patients. Center effect was important. Finally, a vast part of the variability of intubation remained unexplained by patient characteristics.
Trial registration Clinical trials NCT02780466, registered on May 23, 2016. https://clinicaltrials.gov/ct2/show/NCT02780466?term=intubatic&draw=2&rank=1.
Duration of prone position sessions: a prospective cohort study
Authors: Jochmans Sebastien , Mazerand Sandie , Chelly Jonathan , Pourcine Franck , Sy Oumar , Thieulot-Rolin Nathalie , Ellrodt Olivier , Mercier Des Rochettes Emmanuelle , Michaud Gaël , Serbource-Goguel Jean , Vinsonneau Christophe , Vong Ly Van Phach , Monchi Mehran 
Published: May 2020

AbstractBackgroundProne position (PP) is highly recommended in moderate-to-severe ARDS. However, the optimal duration of PP sessions remains unclear. We searched to evaluate the time required to obtain the maximum physiological effect, and to search for parameters related to patient survival in PP.Methods and resultsIt was a prospective, monocentric, physiological study. We included in the study all prone-positioned patients in our ICU between June 2016 and January 2018. Pulmonary mechanics, data from volumetric capnography and arterial blood gas were recorded before prone positioning, 2 h after proning, before return to a supine position (SP) and 2 h after return to SP. Dynamic parameters were recorded before proning and every 30 min during the session until 24 h. 103 patients (ARDS 95%) were included performing 231 PP sessions with a mean length of 21.5 ± 5 h per session. They presented a significant increase in pH, static compliance and PaO2/FiO2with a significant decrease in PaCO2, Pplat, phase 3 slope of the volumetric capnography, PetCO2,VD/VT-phyand ΔP. The beneficial physiological effects continued after 16 h of PP and at least up to 24 h in some patients. The evolution of the respiratory parameters during the first session and also during the pooled sessions did not find any predictor of response to PP, whether before, during or 2 h after the return in SP.ConclusionsPP sessions should be prolonged at least 24 h and be extended in the event that the PaO2/FiO2ratio at 24 h remains below 150, especially since no criteria can predict which patient will benefit or not from it.Trial registrationThe trial has been registered on 28 June 2016 in ClinicalTrials.gov (NCT 02816190) (https://clinicaltrials.gov/ct2/show/NCT02816190?term=propocap&rank=1).
Efficient authentication and re-authentication protocols for 4G/5G heterogeneous networks
Authors: Alezabi Kamal Ali , Hashim Fazirulhisyam , Hashim Shaiful J. , Ali Borhanuddin M. , Jamalipour Abbas 
Published: May 2020

AbstractIn the next-generation heterogeneous wireless networks, designing authentication protocols that meet the demand of mobile users/applications is a challenge. This paper proposes authentication and re-authentication protocols for 4G wireless networks, in particular, LTE-Advanced (LTE-A), WLAN, and WiMAX-Advanced (WiMAX-A) interworking architecture. The proposed protocols are applicable to 5G networks. With the consideration of the existing standard authentication protocols, a new set of authentication and re-authentication protocols has been reinvented to provide fast and secure handovers (HO) in the current 4G and the next 5G networks. The proposed authentication protocols can be invoked when the users perform a vertical HO (between different networks) for the first time, whereas the re-authentication protocols can be invoked when the users perform a horizontal HO (within the same network domain). These protocols provide an efficient method to protect user identity and reduce the burden on the authentication server (AS) during the sequential handovers. The results of the analytical model show that the proposed protocols achieve better performance than standard and other protocols. The reduction of handover cost, handover delay, and energy consumption in the proposed protocols reaches up to 22%, 44%, and 17%, respectively. In addition, the verification tools show that the proposed protocols are secure, dependable, and prevent all types of authentication and secrecy attacks.
New two types of semi-implicit viscosity iterations for approximating the fixed points of nonexpansive operators associated with contraction operators and applications
Authors: Xiong Ting-jian , Lan Heng-you 
Published: May 2020

AbstractMotivated and inspired by the growing contribution with respect to iterative approximations from some researchers in the literature, we design and investigate two types of brand-new semi-implicit viscosity iterative approximation methods for finding the fixed points of nonexpansive operators associated with contraction operators in complete ${\operatorname{CAT}(0)}$CAT(0) spaces and for solving related variational inequality problems. Under some suitable assumptions, strong convergence theorems of the sequences generated by the approximation iterative methods are devised, and a numerical example and some applications to related variational inequality problems are included to verify the effectiveness and practical utility of the convergence theorems. Our main results presented in this paper do not only improve, extend and refine some corresponding consequences in the literature, but also show that the additional variational inequalities, general variational inequality systems and equilibrium problems can be solved via approximation of the iterative sequences. Finally, we provide an open question for future research.
Unique identification of a multi-layered fluid–solid medium
Authors: Cui Yanli , Li Xiliang , Qu Fenglong 
Published: May 2020

AbstractThis paper is concerned with the inverse scattering of time-harmonic acoustic plane waves by a multi-layered fluid–solid medium in the three dimensional space. We establish the global uniqueness in identifying the embedded penetrable solid obstacle, the surrounding fluid medium and its wave number from the acoustic far-field pattern for all incident plane waves at a fixed frequency. The proof depends on constructing different kinds of interior transmission problems in appropriate small domains and the a priori estimates derived for both the elastic wave fields in the embedded solid obstacle and the acoustic wave fields in the surrounding fluid medium.
Pretreatment HIV drug resistance in adults initiating antiretroviral therapy in China, 2017
Authors: Kang Rui-Hua , Liang Shu-Jia , Ma Yan-Ling , Liang Shu , Xiao Lin , Zhang Xin-Hui , Lu Hong-Yan , Xu Xiao-Qin , Luo Shui-Bin , Sun Xiao-Guang , Chen Lin , He Jian-Mei , Wu Guo-Hui , Liao Ling-Jie , Xing Hui , Shao Yi-Ming , Ruan Yu-Hua 
Published: May 2020

AbstractBackgroundAfter the scale-up of antiretroviral therapy (ART) for HIV infected people, increasing numbers of patients have pretreatment drug resistance (PDR). In this study, the prevalence of PDR was evaluated in adults initiating antiretroviral therapy in China.MethodsBlood samples were obtained from 1943 patients who initiated antiretroviral therapy (ART) in 2017 from 13 provinces or cities in China. Pol sequences were used to analyze drug resistance and construct transmission networks. Logistic regression model was used to estimate the potential factors associated with PDR.ResultsIn total, 1711 eligible patients (76.0% male; 87.8% aged ≥ 25 years) were included, of which 117 (6.8%) had PDR. The highest rates of PDR were 12.2% in Liangshan Prefecture of Sichuan and 9.3 and 8.9% in Dehong and Lincang Prefecture of Yunnan. A multivariate logistic regression analysis revealed that PDR was significantly higher among intravenous drug users (adjusted Odds Ratio (aOR) = 2.64, 95%CI: 1.57–4.44) and individuals from Liangshan, Dehong, and Lincang (aOR = 2.04, 95%CI: 1.26–3.30). In total, 754 sequences were used to generate 164 transmission networks. Five transmission networks had two or three sequences containing the same mutations, two networks contained subjects from Liangshan, and one network contained subjects from Dehong.ConclusionsOverall, the PDR prevalence was moderate, with a particularly high prevalence in areas with severe HIV epidemics. These results indicate the importance of continuous PDR monitoring in patients initiating antiretroviral therapy.
Brucellosis in China: history, progress and challenge
Authors: Jiang Hai , O’Callaghan David , Ding Jia-Bo 
Published: May 2020

AbstractBrucellosis is a neglected zoonosis. It causes acute febrile illness and a potentially debilitating chronic infection in humans, and livestock infection has substantial socioeconomic impact. Over the past two decades, improvements have been made to better understand the various aspects of human and animal brucellosis. Meanwhile, especially in the developing world, immense challenges that remain in controlling and eradicating brucellosis are novel diagnostics tools and efficacious vaccines. Here, we will focus on the remarkable issues on epidemiological survey, as well as the priority and challenge of brucellosis in China. Brucellosis will be controlled with meaningful collaboration between local and public partnerships effectively applying a One Health framework.