bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of preferred multimodal ligand‐binding regions on IgG1 FC using nuclear magnetic resonance and molecular dynamics simulations
Authors: Gudhka Ronak B. , Bilodeau Camille L. , McCallum Scott A. , McCoy Mark A. , Roush David J. , Snyder Mark A. , Cramer Steven M.
Published: October 2020

In this study, the binding of multimodal chromatographic ligands to the IgG1 FC domain were studied using nuclear magnetic resonance and molecular dynamics simulations. Nuclear magnetic resonance experiments carried out with chromatographic ligands and a perdeuterated 15N‐labeled FC domain indicated that while single‐mode ion exchange ligands interacted very weakly throughout the FC surface, multimodal ligands containing negatively charged and aromatic moieties interacted with specific clusters of residues with relatively high affinity, forming distinct binding regions on the FC. The multimodal ligand‐binding sites on the FC were concentrated in the hinge region and near the interface of the CH2 and CH3 domains. Furthermore, the multimodal binding sites were primarily composed of positively charged, polar, and aliphatic residues in these regions, with histidine residues exhibiting some of the strongest binding affinities with the multimodal ligand. Interestingly, comparison of protein surface property data with ligand interaction sites indicated that the patch analysis on FC corroborated molecular‐level binding information obtained from the nuclear magnetic resonance experiments. Finally, molecular dynamics simulation results were shown to be qualitatively consistent with the nuclear magnetic resonance results and to provide further insights into the binding mechanisms. An important contribution to multimodal ligand‐FC binding in these preferred regions was shown to be electrostatic interactions and π–π stacking of surface‐exposed histidines with the ligands. This combined biophysical and simulation approach has provided a deeper molecular‐level understanding of multimodal ligand–FC interactions and sets the stage for future analyses of even more complex biotherapeutics.
Analyzing an emerging business ecosystem through M&A activities: The case of the Bioeconomy
Authors: Waßenhoven Anna , Block Carolin , Wustmans Michael , Bröring Stefanie
Published: October 2020

Objectives

The business ecosystem approach has been widely used in research to analyze the role of different actors such as companies and their interdependencies within a specific business environment. However, research dealing with an emerging business ecosystem, where single actors, industry, and market structures are not clearly specified and only gradually evolve, is limited so far. Especially in emerging interindustry business ecosystems, the timely identification of potentially new cooperating sectors is highly relevant, as hitherto separate industry structures might converge. Accordingly, this article adopts an industry perspective allowing for the identification of relevant industry sectors, their respective industry affiliation as well as the development of an emerging business ecosystem.

Methods

In doing so, we propose a conceptual framework for visualizing emerging business ecosystems by drawing upon Merger and Acquisition (M&A) data. While using the case of the highly interdisciplinary emerging Bioeconomy, first, the delineation of relevant Standard Industrial Classification codes, and second, the industry network analysis of M&A data contributes to the visualization of an emerging business ecosystem.

Results

In line with the definition of the Bioeconomy, keystone players as well as most important bridges between other sectors are the chemical and food industry.

Conclusions

The proposed framework can provide insight in the relevance of central industry sectors in forming an emerging interindustry business ecosystem, and it supports the anticipation of converging industries. Finally, it will help policy makers and managers in evaluating resource and knowledge flows across sectors involved within the business ecosystem and in depicting the status‐quo of an emerging business ecosystem.
The role of surgery on the primary tumor site in bladder cancer with distant metastasis: significance of histology type and metastatic pattern
Authors: Wang Ping , Zang Shuang , Li Guangqi , Qu Weiling , Li Shuyao , Qiao Qiao , Jiang Yuanjun
Published: October 2020

Due to the limited data and research on bladder cancer with distant metastasis, the role of surgery on the primary tumor site in metastatic bladder cancer has been controversial. The aim of this study was to investigate the impact of surgery on patients with metastatic bladder cancer and to identify any factors correlated with the treatment efficacy. Using the Surveillance, Epidemiology and End Results dataset, we performed a large population‐based retrospective study. We classified patents with distant metastasis into subgroups according to their histology type and metastatic pattern. Propensity score matching (PSM) was used to balance clinical variables bias in a 1:3 ratio. A total of 2470 patients with distant metastasis were identified from 2010 to 2016. After PSM, the study eventually included 1068 patients in the surgery group and 356 patients in the non‐surgery group. The histologic types, the number of metastatic sites, liver metastasis, surgery, and chemotherapy were significant prognostic variables for patients with distant metastasis before and after PSM. In terms of histologic types, the survival of patients with transitional cell papillary carcinoma, transitional cell non‐papillary carcinoma and adenocarcinoma can be improved by surgery alone, while the survival of patients with squamous cell carcinoma can be improved only by combining chemotherapy and surgery. In terms of the number of metastatic sites, surgery alone was an independent prognostic factor in patients with 1 or 2 metastatic sites. In terms of the specificity of metastatic organs, surgery affected overall survival for patients with bone metastasis only, liver metastasis only and lung metastasis only, but for distant lymph nodes metastasis only. It may be helpful to classify patients with bladder cancer and distant metastasis into different groups by integrating variables including histology types and metastatic patterns to choose appropriate treatment strategies.
Low‐grade gangliogliomas in adults: A population‐based study
Authors: Lin Xiaoning , Huang Rong , Zhang Pengfei , Sun Jin , Dong Guijiang , Huang Yanlin , Tian Xinhua
Published: October 2020

Background

Low‐grade gangliogliomas (GGs) are rare tumors of the central nervous system in adults. This study aims to define their characteristics, prognostic factors, and the impact of different treatment patterns on survival.

Methods

The Surveillance, Epidemiology, and End Results (SEER) database was used to investigate the potential clinicopathological factors of low‐grade GGs in adult patients (age ≥18 years). Kaplan–Meier method and Cox regression model were utilized to evaluate the associations between variables and overall survival (OS).

Results

A total of 703 adult patients diagnosed with low‐grade GGs were identified between 2004 and 2016, with a median follow‐up period of 60.0 months. The median age at diagnosis was 32.0 years, with 50.1% of patients being male, 84.2% white people, and 40.2% of married status. The predominant tumor site was located in temporal lobe (38.8%). The median OS time for the whole cohort was not reached. The 5‐ and 10‐year OS rates for patients underwent gross total resection (GTR) were 92.5% and 87.2%, respectively. Univariate and multivariate analysis showed age, gender, tumor site, and treatment pattern were significant factors for OS. The employment of adjuvant radiotherapy (RT) and/or chemotherapy would significantly shorten OS time.

Conclusions

This is the largest retrospective study of adult low‐grade GGs up to date. Younger age, female gender, temporal lobe location, and GTR indicated better survival. Adjuvant RT and/or chemotherapy should not be considered after whatever surgery in adult patients with low‐grade GGs, unless the malignant transformation has been confirmed.
One‐Photon Excitation Followed by a Three‐Step Sequential Energy–Energy–Electron Transfer Leading to a Charge‐Separated State in a Supramolecular Tetrad Featuring Benzothiazole–Boron‐Dipyrromethene–Zinc Porphyrin–C60
Authors: Badgurjar Deepak , Seetharaman Sairaman , D'Souza Francis , Chitta Raghu
Published: October 2020

A panchromatic triad, consisting of benzothiazole (BTZ) and BF2‐chelated boron‐dipyrromethene (BODIPY) moieties covalently linked to a zinc porphyrin (ZnP) core, has been synthesized and systematically characterized by using 1H NMR spectroscopy, ESI‐MS, UV‐visible, steady‐state fluorescence, electrochemical, and femtosecond transient absorption techniques. The absorption band of the triad, BTZ‐BODIPY‐ZnP, and dyads, BTZ‐BODIPY and BODIPY‐ZnP, along with the reference compounds BTZ‐OMe, BODIPY‐OMe, and ZnP‐OMe exhibited characteristic bands corresponding to individual chromophores. Electrochemical measurements on BTZ‐BODIPY‐ZnP exhibited redox behavior similar to that of the reference compounds. Upon selective excitation of BTZ (≈290 nm) in the BTZ‐BODIPY‐ZnP triad, the fluorescence of the BTZ moiety is quenched, due to photoinduced energy transfer (PEnT) from 1BTZ* to the BODIPY moiety, followed by quenching of the BODIPY emission due to sequential PEnT from the 1BODIPY* moiety to ZnP, resulting in the appearance of the ZnP emission, indicating the occurrence of a two‐step singlet–singlet energy transfer. Further, a supramolecular tetrad, BTZ‐BODIPY‐ZnP:ImC60, was formed by axially coordinating the triad with imidazole‐appended fulleropyrrolidine (ImC60), and parallel steady‐state measurements displayed the diminished emission of ZnP, which clearly indicated the occurrence of photoinduced electron transfer (PET) from 1ZnP* to ImC60. Finally, femtosecond transient absorption spectral studies provided evidence for the sequential occurrence of PEnT and PET events, namely, 1BTZ*‐BODIPY‐ZnP:ImC60→BTZ‐1BODIPY*‐ZnP:ImC60→BTZ‐BODIPY‐1ZnP*:ImC60→BTZ‐BODIPY‐ZnP.+:ImC60.− in the supramolecular tetrad. The evaluated rate of energy transfer, kEnT, was found to be 3–5×1010 s−1, which was slightly faster than that observed in the case of BODIPY‐ZnP and BTZ‐BODIPY‐ZnP, lacking the coordinated ImC60. The rate constants for charge separation and recombination, kCS and kCR, respectively, calculated by monitoring the rise and decay of C60.− were found to be 5.5×1010 and 4.4×108 s−1, respectively, for the BODIPY‐ZnP:ImC60 triad, and 3.1×1010 and 4.9×108 s−1, respectively, for the BTZ‐BODIPY‐ZnP:ImC60 tetrad. Initial excitation of the tetrad, promoting two‐step energy transfer and a final electron‐transfer event, has been successfully demonstrated in the present study.
A pH‐Induced Reversible Conformational Switch Able to Control the Photocurrent Efficiency in a Peptide Supramolecular System
Authors: Kubitzky Sascha , Venanzi Mariano , Biondi Barbara , Lettieri Raffaella , De Zotti Marta , Gatto Emanuela
Published: October 2020

External stimuli are potent tools that Nature uses to control protein function and activity. For instance, during viral entry and exit, pH variations are known to trigger large protein conformational changes. In Nature, also the electron transfer (ET) properties of ET proteins are influenced by pH‐induced conformational changes. In this work, a pH‐controlled, reversible 310‐helix to α‐helix conversion (from acidic to highly basic pH values and vice versa) of a peptide supramolecular system built on a gold surface is described. The effect of pH on the ability of the peptide SAM to generate a photocurrent was investigated, with particular focus on the effect of the pH‐induced conformational change on photocurrent efficiency. The films were characterized by electrochemical and spectroscopic techniques, and were found to be very stable over time, also in contact with a solution. They were also able to generate current under illumination, with an efficiency that is the highest recorded so far with biomolecular systems.
Glycine‐Functionalized CsPbBr3 Nanocrystals for Efficient Visible‐Light Photocatalysis of CO2 Reduction
Authors: Xu Ying , Zhang Wen , Su Ke , Feng You‐Xiang , Mu Yan‐Fei , Zhang Min , Lu Tong‐Bu
Published: October 2020

Capping ligands are indispensable for the preparation of metal‐halide‐perovskite (MHP) nanocrystals (NCs) with good stability; however, the long alkyl‐chain capping ligands in conventional MHP NCs will be unfavorable for CO2 adsorption and hinder the efficient carrier separation on the surface of MHP NCs, leading to inferior catalytic activity in artificial photosynthesis. Herein, CsPbBr3 nanocrystals with short‐chain glycine as ligand are constructed through a facile ligand‐exchange strategy. Owing to the reduced hindrance of glycine and the presence of the amine group in glycine, the photogenerated carrier separation and CO2 uptake capacity are noticeably improved without compromising the stability of the MHP NCs. The CsPbBr3 nanocrystals with glycine ligands exhibit a significantly increased yield of 27.7 μmol g−1 h−1 for photocatalytic CO2‐to‐CO conversion without any organic sacrificial reagents, which is over five times higher than that of control CsPbBr3 NCs with conventional long alkyl‐chain capping ligands.
Prevalence of atrial fibrillation dependent on coronary artery status: Insights from theLIFE‐HeartStudy
Authors: Kornej Jelena , Henger Sylvia , Seewöster Timm , Teren Andrej , Burkhardt Ralph , Thiele Holger , Thiery Joachim , Scholz Markus
Published: October 2020

Background

Coronary artery disease (CAD) is a significant risk factor for atrial fibrillation (AF). Experimental studies demonstrated that atrial ischemia induced by right coronary artery (RCA) stenosis promote AF triggers and development of electro‐anatomical substrate for AF.

Aim

To analyze the association between AF prevalence and coronary arteries status in the LIFE‐Heart Study.

Methods

This analysis included patients with available coronary catheterization data recruited between 2006 and 2014. Patients with acute myocardial infarction were excluded. CAD was defined as stenosis ≥75%, while coronary artery sclerosis (CAS) was defined as non‐critical plaque(s) <75%.

Results

In total, 3.458 patients (median age 63 years, 34% women) were included into analysis. AF was diagnosed in 238 (6.7%) patients. There were 681 (19.7%) patients with CAS and 1.411 (40.8%) with CAD (27.5% with single, 32.4% with double, and 40.1% with triple vessel CAD). In multivariable analysis, there was a significant association between prevalent AF and coronary artery status (OR 0.64, 95% CI 0.53‐0.78,Ptrend < .001). Similarly, AF risk was lower in patients with higher CAD extent (OR 0.54, 95%CI 0.35‐0.83,Ptrend= .005). Compared to single vessel CAD, the risk of AF was lower in double (OR 0.42, 95%CI 0.19‐0.95,P= .037) and triple CAD (OR 0.31, 95%CI 0.13‐0.71,P= .006). Finally, no association was found between AF prevalence and CAD origin among patients with single vessel CAD.

Conclusion

In the LIFE‐Heart Study, CAS but not CAD was associated with increased risk of AF.
Quantifying treatment preferences and their association with financial toxicity in women with breast cancer
Authors: Williams Courtney P. , Gallagher Kathleen D. , Deehr Katie , Aswani Monica S. , Azuero Andres , Daniel Casey L. , Ford Eric W. , Ingram Stacey A. , Balch Alan J. , Rocque Gabrielle B.
Published: October 2020

Background

The objective of the current study was to understand treatment preferences and their association with financial toxicity in Patient Advocate Foundation clients with breast cancer.

Methods

This choice‐based conjoint analysis used data from a nationwide sample of women with breast cancer who received assistance from the Patient Advocate Foundation. Choice sets created from 13 attributes of 3 levels each elicited patient preferences and trade‐offs. Latent class analysis segmented respondents into distinct preference archetypes. The Comprehensive Score for Financial Toxicity (COST) tool captured financial toxicity. Adjusted generalized linear models estimated COST score differences by preference archetype.

Results

Of 220 respondents (for a response rate of 10%), the median age was 58 years (interquartile range, 49‐66 years); 28% of respondents were Black, indigenous, or people of color; and approximately 60% had household incomes <$40,000. The majority of respondents were diagnosed with early‐stage cancer (91%), 38% had recurrent disease, and 61% were receiving treatment. Treatment choice was most affected by preferences related to affordability and impact on activities of daily living. Two distinct treatment preference archetypes emerged. The “cost‐prioritizing group” (75% of respondents) was most concerned about affordability, impact on activities of daily living, and burdening care partners. The “functional independence–prioritizing group” (25% of respondents) was most concerned about their ability to work, physical side effects, and interference with life events. COST scores were found to be similar between the archetypes in adjusted models (cost‐prioritizing group COST score, 12 [95% confidence interval, 9‐14]; and functional independence–prioritizing COST score, 11 [95% confidence interval, 9‐13]).

Conclusions

Patients with breast cancer prioritized affordability or maintaining functional independence when making treatment decisions. Because of this variability, preference evaluation during treatment decision making could optimize patients' treatment experiences.
Defect Engineering on Boron Nitride for O2 Activation and Subsequent Oxidative Desulfurization
Authors: Lv Naixia , Yin Jie , Fu Wendi , Zhang Jinrui , Li Yujun , Jiang Ding , Li Hongping , Zhu Wenshuai
Published: October 2020

The rational design of highly active hexagonal boron nitride (h‐BN) catalysts at the atomic level is urgent for aerobic reactions. Herein, a doping impurity atom strategy is adopted to increase its catalytic activities. A series of doping systems involving O, C impurities and B, N antisites are constructed and their catalytic activities for molecular O2 have been studied by density functional theory (DFT) calculations. It is demonstrated that O2 is highly activated on ON and BN defects, and moderately activated on CB and CN defects, however, it is not stable on NB and OB defects. The subsequent application in oxidative desulfurization (ODS) reactions proves the ON and C‐doped (CB, CN) systems to be good choice for sulfocompounds oxidization, especially for dibenzothiophene (DBT). While the BN antisite is not suitable for such aerobic reaction due to the extremely stable B−O*−B species formed during the oxidation process.
Roadsides provide refuge for orchids: characteristic of the surrounding landscape
Authors: Fekete Réka , Bódis Judit , Fülöp Bence , Süveges Kristóf , Urgyán Renáta , Malkócs Tamás , Vincze Orsolya , Silva Luís , Molnár V. Attila
Published: October 2020

Seminatural habitats are declining throughout the world; thus, the role of small anthropogenic habitats in the preservation of plants is becoming increasingly appreciated. Here, we surveyed the orchid flora of roadside verges in five Central European countries (Austria, Hungary, Romania, Slovakia, and Slovenia) and tested how the surrounding landscape matrix affects the overall number of species and individuals, and also different functional groups of orchids. We found more than 2,000 individuals of 27 orchid species during our surveys. According to our results, the increasing coverage of agricultural and urban areas negatively affects both the number of orchid species and individuals on roadsides. Our study further suggests that differences in the surrounding habitats affect which species are found on roadsides, since the increasing coverage of grasslands or forested areas around orchid occurrences had a significant positive effect on the number of grassland or forest‐dwelling species and individuals, respectively. Most variance in orchid numerosity and diversity was explained by the cover of the suitable habitat types of the respective taxa in the surrounding landscape of the sampling points. This highlights the importance of roadsides acting as refugia for numerous species and valuable plant communities as well as in supporting biodiversity in general.
A novel single‐wire communication method using analog wave for a universal connector
Authors: Tanno Yoshinobu , Hayashi Takafumi
Published: October 2020

Various devices such as computer and peripheral device contribute to our lives. Because there is a wide variety of devices, the types of device connector standard are increasing. A converter for converting the electrical signal of the pin in a connector is required for communication with different connector standard. However, there is a problem that the number of converters for interconnection continues to increase when the connector standard continues to increase. This paper proposes a communication method for the universal connector that can automatically communicate between different connector standards without the converter. The universal connector negotiates at the beginning of the connection using the electrical signal of the pin in the connector. The negotiation using the electrical signal of the pin requires a single‐wire communication. Machine with single‐wire communication requires to understand connection partner's performance because available machines with the universal connector do not strictly limit the partner. In this paper, we propose a novel single‐wire communication method that each machine understands performance of connection partner for the universal connector. The performance of the proposed method was evaluated by simulation.
Cost‐effectiveness of adding dapagliflozin to standard treatment for heart failure with reduced ejection fraction patients in China
Authors: Yao Younan , Zhang Rongcheng , An Tao , Zhao Xinke , Zhang Jian
Published: October 2020

Aims

This study was to determine the cost‐effectiveness of dapagliflozin in heart failure with reduced ejection fraction (HFrEF) patients in China from a perspective of health care payers.

Methods and results

We built a Markov model to perform a cost‐effectiveness analysis comparing standard treatment + dapagliflozin (10 mg, q.d.) with standard treatment for HFrEF. The base case in our simulation was a 65‐year‐old HFrEF patient and was modelled over 15 years. Inputs of the model were derived from the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial and other relevant data from China. Costs, quality‐adjusted life year (QALY), and incremental cost‐effectiveness ratio (ICER) were estimated for adding dapagliflozin relative to standard treatment. Costs and QALY were discounted at a 4.2% rate annually. All costs are presented in 2017 US dollars. Dapagliflozin would be considered very cost‐effective if the ICER was lower than a willingness‐to‐pay (WTP) threshold of $8573.4. Uncertainty was assessed in our model using one‐way, two‐way, and probabilistic sensitivity analysis (PSA). In our base case, compared with standard treatment, adding dapagliflozin was more expensive ($5829.4 vs. $4377.1) but more effective (4.82 vs. 4.44 QALYs). The respondent ICER was $3827.6 per QALY gained at 15‐year follow‐up. When the simulated horizon was longer than 3.5 years, the respondent ICER became lower than the WTP threshold. The inputs with the largest impact on ICER were the cost of dapagliflozin, the cardiovascular mortality in both groups, and the cost of hospitalization for heart failure. Most results of sensitivity analysis were robust. PSA showed a similar result as the base case (ICER = $4412.5 per QALY gained). In Monte Carlo simulation, at a WTP threshold of $8573.4 per QALY, dapagliflozin was considered very cost‐effective in 53.10% of the simulations.

Conclusions

Dapagliflozin was a very cost‐effective treatment option for HFrEF patients in China according to the result of our model. Our findings will help doctors and health care payers to make decisions in clinical practice. Future real‐world studies of cost‐effectiveness of dapagliflozin based on Chinese population were also needed.
MitraClip implantation followed by insertion of a left ventricular assist device in patients with advanced heart failure
Authors: Kreusser Michael M. , Hamed Sonja , Weber Andreas , Schmack Bastian , Volz Martin J. , Geis Nicolas A. , Grossekettler Leonie , Pleger Sven T. , Ruhparwar Arjang , Katus Hugo A. , Raake Philip W.
Published: October 2020

Aims

Mitral valve regurgitation (MR) is common in patients with advanced heart failure (HF). Percutaneous mitral valve repair (PMVR) via MitraClip (MC) has emerged as a feasible treatment strategy for these high‐risk patients. However, as HF often further progresses, there is a frequent need for left ventricular assist device (LVAD) implantation in these patients. We aimed to investigate whether prior MC implantation affects the subsequent LVAD implantation and outcome.

Methods and results

Thirty‐seven patients with advanced HF and significant MR who underwent LVAD implantation were retrospectively analysed. Follow‐up data were collected at 1 year after LVAD implantation. Primary endpoint was all‐cause mortality. Secondary endpoint included peri‐operative parameters and clinical development depicted as New York Heart Association (NYHA) class and Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) level. Seventeen patients initially received a MC device (MC group), resulting in a significant reduction in MR grade. After MC, NYHA class and INTERMACS level further worsened, leading to subsequent LVAD implantation after a median time of 475 days in the MC group. At LVAD implantation, overall characteristics were comparable with those of the patients undergoing LVAD implantation without prior MC placement (no‐MC group). Procedural data revealed a higher incidence of right ventricular (RV) failure needing mechanical RV assistance and a longer need for nitric oxide ventilation in the MC group after LVAD implantation. One‐year survival was slightly better in the no‐MC group compared with the MC group [41% (n = 7/17) vs. 65% (n = 13/20); P = 0.15], albeit event‐free survival was comparable between both groups, MC and no‐MC.

Conclusions

LVAD implantation after MC is feasible and safe. However, in patients with advanced HF and severe MR, PMVR may only delay a needed LVAD implantation and thereby lead to poorer peri‐operative RV function and impaired outcome. Arguably, these patients might benefit from the timely management of advanced HF by the means of early LVAD implantation or heart transplantation.
Novel Designing of Chemically Modified Electrode (CME) of the Bio‐MOF‐1 for the Detection of Dopamine Based on Inhibition of [Ru(bpy)3]2+/DBAE System
Authors: Dong X. Y. , Zhang R. Z. , Zhang T. K. , Liu F. Y.
Published: October 2020

Metal organic frameworks (MOFs) have attracted extensive attention in electrochemical research fields due to their high surface area and controlled porosity. Current study is design to investigate the ECL performance of the chemically modified electrode (CME) based on the bio‐MOF‐1, a porous zinc‐adenine framework, which loaded ruthenium complex and employed for the detection of dopamine (DA). The composite material [Ru(bpy)3]2+@bio‐MOF‐1 (Ru‐bMOF) modified carbon glassy electrode (Ru‐bMOF/GCE) exhibited an excellent ECL performance having a linear co‐efficient response (R2=0.9968) for 2‐(dibutyl amino) ethanol (DBAE), a classical ECL co‐reactant was obtained over a concentration range of 1.0×10−9 M to 1.0×10−4 M in 0.10 M pH=6.0 phosphate buffer solution (PBS). Furthermore, DA was detected based on its inhibition effect on [Ru(bpy)3]2+/DBAE system. Compared to traditional analytical methods, this method has various advantages such as simple electrode preparation, quick response, high reproducibility (RSD<2.0 %), low limit of detection (LOD=1.0×10−10 mol/L). This chemical investigated modified electrode had exploited potential for detection of DA.
Lactobacillus plantarum 06CC2 reduces hepatic cholesterol levels and modulates bile acid deconjugation in Balb/c mice fed a high‐cholesterol diet
Authors: Yamasaki Masao , Minesaki Mikako , Iwakiri Asuka , Miyamoto Yuko , Ogawa Kenjiro , Nishiyama Kazuo , Tsend‐Ayush Chuluunbat , Oyunsuren Tsendesuren , Li Yiran , Nakano Tomoki , Takeshita Masahiko , Arima Yuo
Published: October 2020

Previous study suggested that dietary intake of Lactobacillus plantarum 06CC2 (LP06CC2) isolated from Mongolian dairy products showed various health beneficial effects. Here, the effect of LP06CC2 on the cholesterol metabolism in mice fed a cholesterol‐loaded diet was evaluated. Cholesterol and LP06CC2 were incorporated into the AIN93G‐based diet to evaluate the effect on cholesterol metabolism in Balb/c mice. Serum and liver cholesterol levels were significantly increased in mice fed a cholesterol‐loaded diet whereas the LP06CC2 ingestion suppressed the increase of liver cholesterol. LP06CC2 suppressed the increase of the hepatic damage indices. The increase of the cecal content and fecal butyrate were observed in mice fed LP06CC2. The analysis of bile acids clearly showed that LP06CC2 increased their deconjugation indicating the decrease of bile acid absorption. The protein expression of hepatic Cyp7A1 was also suppressed by LP06CC2 in mice fed cholesterol. Finally, in vitro studies showed that LP06CC2 had the most potent ability to deconjugate bile acids using glycocholate among the tested probiotic lactic acid bacteria isolated from Mongolian dairy products. Taken together, LP06CC2 is a promising microorganism for the reduction of the cholesterol pool via modulation of bile acid deconjugation.
Hospital entrance smoking is reduced by broadcasting recorded antitobacco messages from Australian primary school children over entrance public address system
Authors: Webb Ashley , Tascone Belinda , Wickham Lucy , Webb Gemma , Wijeyaratne Avisha , Boyd David Thomas , Leong Samuel
Published: October 2020

Issue addressed

Smoking near hospital entrances occurs frequently despite smoke‐free policies, resulting in multiple issues including second‐hand smoke exposure (SHS) to vulnerable populations. Primary school children were engaged through their health curriculum to produce antismoking audio recordings for broadcast over a hospital entrance loudspeaker system to determine if this reduced smoking.

Method

Students produced original recordings against hospital grounds smoking during class workshops, from which a collection (n = 16) was selected. Episodes of entrance smoking and total entrance traffic were recorded using security camera infrastructure over a 5‐week period. A computer‐controlled entrance loudspeaker played a message which was followed by silence until a new (different) message was played. Intensity of messaging was moderate in week 3 (every 5 minutes), increasing to high in week 4 (3 minutely) and compared to no messages (weeks 1‐2 preintervention) and week 5 (postintervention).

Results

Smokers presented 316 times, smoking 523 cigarettes over 155 hours of observation (patients 70.6%, visitors 29.4%). SHS exposure was high given 172 others used the entrance/hour. Smoking was highest in the preintervention period (weeks 1‐2), median five cigarettes/hr [IQR,3‐7 (min = 0, max = 12)], falling to four cigarettes/hr during 5‐minutely broadcasts [IQR,2‐5 (min = 1, max = 14)] (P = .06), but zero cigarettes/hr during 3‐minutely broadcasts [IQR,0‐1(min = 0, max = 7)] (P < .0001). Postintervention (no broadcasts), smoking increased from zero to 1 cigarette/hr [IQR,0‐3 (min = 0, max = 5)]; (P = .052). Nonsmoker movements did not change significantly between each period.

Conclusion

Intensive (3 minutely) broadcasting of short antismoking messages significantly reduced hospital entrance smoking.

So what?

Health services can positively interact with the health curriculum of primary schools against tobacco use while developing low‐cost strategies to effectively deter entrance smoking.
Increased S1P expression in osteoclasts enhances bone formation in an animal model of Paget's disease
Authors: Nagata Yuki , Miyagawa Kazuaki , Ohata Yasuhisa , Petrusca Daniela N. , Pagnotti Gabriel M. , Mohammad Khalid S. , Guise Theresa A. , Windle Jolene J. , David Roodman G. , Kurihara Noriyoshi
Published: October 2020

Paget's disease (PD) is characterized by increased numbers of abnormal osteoclasts (OCLs) that drive exuberant bone formation, but the mechanisms responsible for the increased bone formation remain unclear. We previously reported that OCLs from 70% of PD patients express measles virus nucleocapsid protein (MVNP), and that transgenic mice with targeted expression of MVNP in OCLs (MVNP mice) develop bone lesions and abnormal OCLs characteristic of PD. In this report, we examined if OCL‐derived sphingosine‐1‐phosphate (S1P) contributed to the abnormal bone formation in PD, since OCL‐derived S1P can act as a coupling factor to increase normal bone formation via binding S1P‐receptor‐3 (S1PR3) on osteoblasts (OBs). We report that OCLs from MVNP mice and PD patients expressed high levels of sphingosine kinase‐1 (SphK‐1) compared with wild‐type (WT) mouse and normal donor OCLs. SphK‐1 production by MVNP‐OCLs was interleukin‐6 (IL‐6)‐dependent since OCLs from MVNP/IL‐6−/− mice expressed lower levels of SphK‐1. Immunohistochemistry of bone biopsies from a normal donor, a PD patient, WT and MVNP mice confirmed increased expression levels of SphK‐1 in OCLs and S1PR3 in OBs of the PD patient and MVNP mice compared with normal donor and WT mice. Further, MVNP‐OCLs cocultured with OBs from MVNP or WT mice increased OB‐S1PR3 expression and enhanced expression of OB differentiation markers in MVNP‐OBs precursors compared with WT‐OBs, which was mediated by IL‐6 and insulin‐like growth factor 1 secreted by MVNP‐OCLs. Finally, the addition of an S1PR3 antagonist (VPC23019) to WT or MVNP‐OBs treated with WT and MVNP‐OCL‐conditioned media (CM) blocked enhanced OB differentiation of MVNP‐OBs treated with MVNP‐OCL‐CM. In contrast, the addition of the SIPR3 agonist, VPC24191, to the cultures enhanced osterix and Col‐1A expression in MVNP‐OBs treated with MVNP‐OCL‐CM compared with WT‐OBs treated with WT‐OCL‐CM. These results suggest that IL‐6 produced by PD‐OCLs increases S1P in OCLs and S1PR3 on OBs, to increase bone formation in PD.
Functional aspects of primary cilium in signaling, assembly and microenvironment in cancer
Authors: Wang Bo , Liang Zheyong , Liu Peijun
Published: October 2020

The primary cilium is an antennae‐like structure extent outside the cell surface. It has an important role in regulating cell‐signaling transduction to affect proliferation, differentiation and migration. Evidence is accumulating that ciliary defects lead to ciliopathies and ciliary deregulation also play crucial roles in cancer formation and progression. Interestingly, restoring the cilia can suppress proliferation in some cancer cell. However, t he role of primary cilia in cancer still be debated. In this article, we review the role of the primary cilium in cancer through architecture, signaling pathways, cilia assembly and disassembly regulators, and summarized the new findings of the primary cilium in tumor microenvironments and different cancers, highlighting novel possibilities for therapeutic target in cancer.
Carbon nanotube field effect transistor (CNTFET) operational transconductance amplifier (OTA) based design of high frequency memristor emulator
Authors: Khurshid Tabassum , Fatima Syed , Khanday Farooq Ahmad , Bashir Faisal , Zahoor Furqan , Hussin Fawnizu Azmadi
Published: October 2020

The design and simulation of high frequency memristor emulator using carbon nanotube field effect transistor (CNTFET) based Operational Transconductance Amplifier (OTA) has been presented out in this paper. The proposed memristor emulator design consists of two CNTFET‐OTAs and one capacitor with both grounded and floating topologies available for applications. The proposed CNTFET memristor design emulator outperforms the conventional complementary metal oxide semiconductor (CMOS) based memristor emulator topologies. The performance comparison with the reported memristor emulator designs reveals that the proposed grounded and floating memristor design can work over a frequency range of 1 GHz and 10 MHz respectively in comparison to conventional CMOS based design, which works over a maximum range of 8 MHz and 0.4 MHz for grounded and floating memristor designs respectively. The proposed memristor emulator circuit also offers electronic tunability of the memristance which is important for digitally programmable application of memristors.
Estimating publication bias in meta‐analyses of peer‐reviewed studies: A meta‐meta‐analysis across disciplines and journal tiers
Authors: Mathur Maya B. , VanderWeele Tyler J.
Published: October 2020

Selective publication and reporting in individual papers compromise the scientific record, but are meta‐analyses as compromised as their constituent studies? We systematically sampled 63 meta‐analyses (each comprising at least 40 studies) in PLoS One, top medical journals, top psychology journals, and Metalab, an online, open‐data database of developmental psychology meta‐analyses. We empirically estimated publication bias in each, including only the peer‐reviewed studies. Across all meta‐analyses, we estimated that “statistically significant” results in the expected direction were only 1.17 times more likely to be published than “nonsignificant” results or those in the unexpected direction (95% CI: [0.93, 1.47]), with a confidence interval substantially overlapping the null. Comparable estimates were 0.83 for meta‐analyses in PLoS One, 1.02 for top medical journals, 1.54 for top psychology journals, and 4.70 for Metalab. The severity of publication bias did differ across individual meta‐analyses; in a small minority (10%; 95% CI: [2%, 21%]), publication bias appeared to favor “significant” results in the expected direction by more than threefold. We estimated that for 89% of meta‐analyses, the amount of publication bias that would be required to attenuate the point estimate to the null exceeded the amount of publication bias estimated to be actually present in the vast majority of meta‐analyses from the relevant scientific discipline (exceeding the 95th percentile of publication bias). Study‐level measures (“statistical significance” with a point estimate in the expected direction and point estimate size) did not indicate more publication bias in higher‐tier versus lower‐tier journals, nor in the earliest studies published on a topic versus later studies. Overall, we conclude that the mere act of performing a meta‐analysis with a large number of studies (at least 40) and that includes non‐headline results may largely mitigate publication bias in meta‐analyses, suggesting optimism about the validity of meta‐analytic results.
Circulating tumor cell analysis in locally advanced and metastatic squamous cell carcinoma of the head and neck
Authors: Harris Ethan J. , Huang Julian , Carroll Erin , Lowe Alarice C. , Chau Nicole G. , Rabinowits Guilherme , Haddad Robert , Hanna Glenn J. , Haddad Tyler , Sanborn Matthew , Kacew Alec , Lorch Jochen
Published: October 2020

Background

Circulating tumors cells (CTCs) are considered an early step towards metastasis and have been linked to poor prognosis in several types of cancer. CTCs in squamous cell carcinoma of the head and neck (SCCHN) have an unclear role.

Methods

In this prospective study, patients with locally advanced or metastatic SCCHN had CTC counts assessed before starting systemic treatment using the CellSearch System. Select cases also had sequential CTC evaluation. Presence of CTCs was correlated with patient characteristics and outcomes.

Results

Forty‐eight patients enrolled, and 36 had evaluable clinical data and baseline CTC counts. Twenty‐five patients had locally advanced disease (LAD) and 11 had metastatic disease. ≥1 CTCs were detected in six patients with LAD (24%) and four with metastatic disease (36%). On univariate analysis, smoking was associated with CTCs.

Conclusion

CTCs are not associated with prognosis in patients with LAD and metastatic disease; however, they are present in this patient population, and ≥1 CTCs is associated with a history of smoking.

Level of evidence

1b; individual prospective cohort study.
The Impact of Dabigatran Treatment on Sinusoidal Protection Against Hepatic Ischemia/Reperfusion Injury in Mice
Authors: Noguchi Daisuke , Kuriyama Naohisa , Hibi Taemi , Maeda Koki , Shinkai Toru , Gyoten Kazuyuki , Hayasaki Aoi , Fujii Takehiro , Iizawa Yusuke , Tanemura Akihiro , Murata Yasuhiro , Kishiwada Masashi , Sakurai Hiroyuki , Mizuno Shugo
Published: October 2020

Thrombin is a key player in the coagulation cascade, and it is attracting much attention as a promotor of cellular injured signaling. In ischemia/reperfusion injury (IRI), which is a severe complication of liver transplantation, thrombin may also promote tissue damage. The aim of this study is to reveal whether dabigatran, a direct thrombin inhibitor, can attenuate hepatic IRI with focusing on a protection of sinusoidal endothelial cells (SECs). Both clinical patients who underwent hepatectomy and in vivo mice model of 60‐minute hepatic partial‐warm IRII, thrombin generation was evaluated before and after IRI. In next study, IRI mice were treated with or without dabigatran. In addition, hepatic SECs and hepatocytes pretreated with or without dabigatran were incubated in hypoxia/reoxygenation (H‐R) environment in vitro. Thrombin generation evaluated by thrombin–antithrombin complex (TAT) was significantly enhanced after IRI in the clinical study and in vivo study. Thrombin exacerbated lactate dehydrogenase cytotoxicity levels in a dose‐dependent manner in vitro. In an IRI model of mice, dabigatran treatment significantly improved liver histological damage, induced sinusoidal protection, and provided both antiapoptotic and anti‐inflammatory effects. Furthermore, dabigatran not only enhanced endogenous thrombomodulin (TM) but also reduced excessive serum high‐mobility group box‐1 (HMGB‐1). In H‐R models of SECs, not hepatocytes, pretreatment with dabigatran markedly attenuated H‐R damage, enhanced TM expression in cell lysate, and decreased extracellular HMGB‐1. The supernatant of SECs pretreated with dabigatran protected hepatocytes from H‐R damage and cellular death. Thrombin exacerbated hepatic IRI, and excessive extracellular HMGB‐1 caused severe inflammation‐induced and apoptosis‐induced liver damage. In this situation, dabigatran treatment improved vascular integrity via sinusoidal protection and degraded HMGB‐1 by endogenous TM enhancement on SECs, greatly ameliorating hepatic IRI.
Polyethyleneimine‐CpG Nanocomplex as an In Situ Vaccine for Boosting Anticancer Immunity in Melanoma
Authors: Xu Yudi , Ma Sheng , Si Xinghui , Zhao Jiayu , Yu Haiyang , Ma Lili , Song Wantong , Tang Zhaohui
Published: October 2020

Cancer immunotherapy is redefining the field of cancer therapy. However, current cancer immunotherapies are limited by insufficient immune activation, which results in low response rate. Herein, polyethyleneimine‐CpG nanocomplex (CpG@PEI) is reported as an in situ vaccine for boosting anticancer immunity in melanoma. CpG, a Toll‐like receptor (TLR) 9 agonist, can activate antigen‐presenting cells and increase the expression of costimulatory molecules, while PEI can help to enhance the stability and cellular internalization of CpG. It is proved that PEI loading can significantly enhance the cellular internalization and immune stimulation ability of CpG, and the CpG@PEI nanocomplex can effectively inhibit murine B16F10 melanoma growth after intratumoral injection. Further analysis reveals that this CpG@PEI nanocomplex therapy elicits both innate and adaptive immunity, with much increased natural killer (NK) cells and T cells infiltration in the tumor, as well as CD80 expression on the dendritic cells (DCs). This study will inspire more attempts in directly using single nanoparticle‐loaded pattern recognition receptor (PRR) agonists for cancer immunotherapy.
Three‐dimensional whole‐brain simultaneous T1, T2, and T1ρquantification using MR Multitasking: Method and initial clinical experience in tissue characterization of multiple sclerosis
Authors: Ma Sen , Wang Nan , Fan Zhaoyang , Kaisey Marwa , Sicotte Nancy L. , Christodoulou Anthony G. , Li Debiao
Published: October 2020

Purpose

To develop a 3D whole‐brain simultaneous T1/T2/T1ρquantification method with MR Multitasking that provides high quality, co‐registered multiparametric maps in 9 min.

Methods

MR Multitasking conceptualizes T1/T2/T1ρrelaxations as different time dimensions, simultaneously resolving all three dimensions with a low‐rank tensor image model. The proposed method was validated on a phantom and in healthy volunteers, comparing quantitative measurements against corresponding reference methods and evaluating the scan‐rescan repeatability. Initial clinical validation was performed in age‐matched relapsing‐remitting multiple sclerosis (RRMS) patients to examine the feasibility of quantitative tissue characterization and to compare with the healthy control cohort. The feasibility of synthesizing six contrast‐weighted images was also examined.

Results

Our framework produced high quality, co‐registered T1/T2/T1ρmaps that closely resemble the reference maps. Multitasking T1/T2/T1ρmeasurements showed substantial agreement with reference measurements on the phantom and in healthy controls. Bland‐Altman analysis indicated good in vivo repeatability of all three parameters. In RRMS patients, lesions were conspicuously delineated on all three maps and on four synthetic weighted images (T2‐weighted, T2‐FLAIR, double inversion recovery, and a novel “T1ρ‐FLAIR” contrast). T1 and T2 showed significant differences for normal appearing white matter between patients and controls, while T1ρshowed significant differences for normal appearing white matter, cortical gray matter, and deep gray matter. The combination of three parameters significantly improved the differentiation between RRMS patients and healthy controls, compared to using any single parameter alone.

Conclusion

MR Multitasking simultaneously quantifies whole‐brain T1/T2/T1ρand is clinically promising for quantitative tissue characterization of neurological diseases, such as MS.
Results on approximate controllability results for second‐order Sobolev‐type impulsive neutral differential evolution inclusions with infinite delay
Authors: Vijayakumar V. , Panda Sumati Kumari , Nisar Kottakkaran Sooppy , Baskonus Haci Mehmet
Published: October 2020

In this article, we determine a set of appropriate conditions for approximate controllability of second‐order Sobolev‐type impulsive neutral differential evolution inclusions with infinite delay. We verify the main results by applying ideas about the cosine function, sine functions, and fixed point approach. Next, we continue the discussion to the nonlocal second‐order Sobolev‐type differential system. In the end, we provide a theoretical application to assist in the effectiveness of our discussion.