bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Artificial Hemoprotein with Inducible Peroxidase‐ and Monooxygenase‐Like Activities
Authors: Kariyawasam Kalani , Di Meo Thibault , Hammerer Fabien , Valerio‐Lepiniec Marie , Sciortino Giuseppe , Maréchal Jean‐Didier , Minard Philippe , Mahy Jean‐Pierre , Urvoas Agathe , Ricoux Rémy 
Published: June 2020

AbstractA novel inducible artificial metalloenzyme obtained by covalent attachment of a manganese(III)‐tetraphenylporphyrin (MnTPP) to the artificial bidomain repeat protein, (A3A3′)Y26C, is reported. The protein is part of the αRep family. The biohybrid was fully characterized by MALDI‐ToF mass spectrometry, circular dichroism and UV/Vis spectroscopies. The peroxidase and monooxygenase activities were evaluated on the original and modified scaffolds including those that have a) an additional imidazole, b) a specific αRep bA3‐2 that is known to induce the opening of the (A3A3′) interdomain region and c) a derivative of the αRep bA3‐2 inducer extended with a His6‐Tag (His6‐bA3‐2). Catalytic profiles are highly dependent on the presence of co‐catalysts with the best activity obtained with His6‐bA3‐2. The entire mechanism was rationalized by an integrative molecular modeling study that includes protein–ligand docking and large‐scale molecular dynamics. This constitutes the first example of an entirely artificial metalloenzyme with inducible peroxidase and monooxygenase activities, reminiscent of allosteric regulation of natural enzymatic pathways.
LGBTQ+ in STEM: Visibility and Beyond
Authors: Unsay Joseph D. 
Published: June 2020

AbstractLesbian, gay, bisexual, trans, queer (LGBTQ+, “+”=plus other sexes, gender identities, and sexual orientation) people in the STEM fields (STEM=science, technology, engineering, and mathematics) continue to experience discrimination in their workplace. In the last decade, the clamor for safe and diverse spaces continue to rise. Indeed, social media plays a huge part on increasing visibility of the LGBTQ+ community in STEM. LGBTQ+ scientists have not only promoted discourse and raised concerns to the online community, but more importantly, supported each other in platforms such as Twitter. Beyond social media, work at the institutes by LGBTQ+ individuals are also bearing fruit. This piece explores the grassroots work of scientists as they work hand‐in‐hand with their institute staff and leadership to promote diversity and inclusivity within and beyond their community.
Simulation of binary particle segregation for bubbling fluidized beds using polydispersed structure‐based drag model extended from a monodispersed model
Authors: Jia Jibin , Li Hongzhong , Zou Zheng , Liu Wenming , Zhu Qingshan 
Published: June 2020

AbstractA bubble structure‐based drag model developed for the monodispersed system has been extended to simulate bi‐dispersed bubbling fluidized beds. Both dense phase and dilute phase are considered to be comprised of two types of particles with different sizes. The derivation of the structure‐based drag coefficient for individual particle based on the force equilibrium principle is proved to be independent of the volume fractions (εsi) of particle i. The multi‐fluid model in the commercial software Ansys Fluent is employed to evaluate the polydispersed drag model for the segregation of binary gas‐particle flows in a bubbling fluidized bed. It is shown that the simulation results predicted by the new structure‐based drag model are in reasonable agreement with experimental data with a 6.34% root mean square error (RMSE). The new structure‐based model can capture the particle distribution at the top region of the fluidized bed well. The bubble behaviour can also be captured by the new model well.
Development of Biomimetic Synthesis of Propindilactone G†
Authors: Wang Yu , Chen Bo , He Xubiao , Gui Jinghan 
Published: June 2020

Summary of main observation and conclusionThe natural product propindilactone G is a complex Schisandra nortriterpenoid with a unique 5/5/7/6/5 pentacyclic framework. This full paper describes the development of concise biomimetic synthesis of propindilactone G from a known steroid lactone. The key C19‐OH intermediate was synthesized via Breslow and Suárez radical remote C—H functionalizations. Wagner‐Meerwein rearrangement was subsequently utilized for the expansion of the B ring. To invert the configuration of the C10 tertiary alcohol, an intramolecular peroxide cyclization catalyzed by BF3·Et2O was devised. The 5/5 fused lactone system was then assembled in a biomimetic transesterification/oxa‐Michael addition sequence. Our work should provide experimental support for the proposed biosynthetic pathway and facilitate investigation of the biological activities of propindilactone G.
Hypothesis‐free deep survival learning applied to the tumour microenvironment in gastric cancer
Authors: Meier Armin , Nekolla Katharina , Hewitt Lindsay C , Earle Sophie , Yoshikawa Takaki , Oshima Takashi , Miyagi Yohei , Huss Ralf , Schmidt Günter , Grabsch Heike I 
Published: June 2020

AbstractThe biological complexity reflected in histology images requires advanced approaches for unbiased prognostication. Machine learning and particularly deep learning methods are increasingly applied in the field of digital pathology. In this study, we propose new ways to predict risk for cancer‐specific death from digital images of immunohistochemically (IHC) stained tissue microarrays (TMAs). Specifically, we evaluated a cohort of 248 gastric cancer patients using convolutional neural networks (CNNs) in an end‐to‐end weakly supervised scheme independent of subjective pathologist input. To account for the time‐to‐event characteristic of the outcome data, we developed new survival models to guide the network training. In addition to the standard H&E staining, we investigated the prognostic value of a panel of immune cell markers (CD8, CD20, CD68) and a proliferation marker (Ki67). Our CNN‐derived risk scores provided additional prognostic value when compared to the gold standard prognostic tool TNM stage. The CNN‐derived risk scores were also shown to be superior when systematically compared to cell density measurements or a CNN score derived from binary 5‐year survival classification, which ignores time‐to‐event. To better understand the underlying biological mechanisms, we qualitatively investigated risk heat maps for each marker which visualised the network output. We identified patterns of biological interest that were related to low risk of cancer‐specific death such as the presence of B‐cell predominated clusters and Ki67 positive sub‐regions and showed that the corresponding risk scores had prognostic value in multivariate Cox regression analyses (Ki67&CD20 risks: hazard ratio (HR) = 1.47, 95% confidence interval (CI) = 1.15–1.89,p= 0.002; CD20&CD68 risks: HR = 1.33, 95% CI = 1.07–1.67,p= 0.009). Our study demonstrates the potential additional value that deep learning in combination with a panel of IHC markers can bring to the field of precision oncology.
Review paper on WPW and athletes: Let sleeping dogs lie?
Authors: Leung Lisa W.M. , Gallagher Mark M. 
Published: June 2020

AbstractAccessory pathways are present in 1 in 300 young individuals. They are often asymptomatic and potentially lethal arrhythmias may be the first presentation. During long‐term follow‐up, up to 20% of asymptomatic individuals with pre‐excitation go on to develop an arrhythmia and the absence of traditional clinical and electrophysiological high‐risk markers does not guarantee the “safe” nature of an accessory pathway. The widespread availability of permanent cure for the condition at low risk by catheter ablation, creates an incentive to screen for accessory pathways with a 12‐lead ECG, particularly in individuals who are perceived to be at increased risk, such as athletes and high‐risk professions. We review the existing literature on the assessment and management of accessory pathways (Wolff‐Parkinson‐White [WPW] syndrome) and discuss its implications for the young athletic population.
Effects of Multiple‐Dose Administration of Aprocitentan on the Pharmacokinetics of Rosuvastatin
Authors: Sidharta Patricia N. , Dingemanse Jasper 
Published: June 2020

AbstractAprocitentan is an investigational, orally active, dual, endothelin receptor antagonist that targets a novel pathway in the treatment of difficult‐to‐control (resistant) hypertension. The drug‐drug interaction potential of aprocitentan on the breast cancer resistance protein (BCRP) transporter substrate rosuvastatin was investigated in this single‐center, open‐label, single‐sequence study. Twenty healthy male subjects received a single dose of 10‐mg rosuvastatin on days 1 and 13 followed by pharmacokinetic and tolerability assessments for up to 120 hours. From day 5 to day 17, subjects received 25 mg of aprocitentan once daily. Seventeen of 20 enrolled subjects completed the treatment. At steady state, aprocitentan did not affect the pharmacokinetics of rosuvastatin in a clinically relevant way. The maximum plasma concentration was increased by 40% with a 90% confidence interval of 1.19 to 1.65. However, the ratio of the geometric means for both area under the plasma concentration–time curve from time 0 to time t and area under the plasma concentration–time curve from time 0 to infinity was close to 1 with the 90% confidence interval within a reference interval of 0.80 to 1.25.Adverse events leading to study discontinuation were reported in 2 subjects. Overall, the combination of rosuvastatin and aprocitentan was well tolerated. Based on these data, aprocitentan does not affect BCRP and can be administered concomitantly with drugs dependent on BCRP transport.
Humanized Mouse Models for Evaluation of PSC Immunogenicity
Authors: Hermsen Jack , Brown Matthew E. 
Published: June 2020

AbstractNew human pluripotent stem cell (hPSC)‐derived therapies are advancing to clinical trials at an increasingly rapid pace. In addition to ensuring that the therapies function properly, there is a critical need to investigate the human immune response to these cell products. A robust allogeneic (or autologous) immune response could swiftly eliminate an otherwise promising cell therapy, even in immunosuppressed patients. In coming years, researchers in the regenerative medicine field will need to utilize a number of in vitro and in vivo assays and models to evaluate and better understand hPSC immunogenicity. Humanized mouse models—mice engrafted with functional human immune cell types—are an important research tool for investigating the mechanisms of the adaptive immune response to hPSC therapies. This article provides an overview of humanized mouse models relevant to the study of hPSC immunogenicity and explores central considerations for investigators seeking to utilize these powerful models in their research. © 2020 Wiley Periodicals LLC.
Design of low power approximate floating‐point adders
Authors: Omidi Reza , Sharifzadeh Sepehr 
Published: June 2020

SummaryDue to the increasing demands for more power in data intensive computing, low power design methodologies play a very important role in these systems. For noncritical data, the approximate computing that significantly reduces the power can be used. In this paper, an approximate floating‐point adder is proposed by designing an inexact mantissa adder and exponent subtractor. The results indicate that the power consumption and delay of the proposed approximate floating‐point adder have been decreased by 37% and 62% compared with the IEEE‐754 single‐precision floating‐point (FP) adder. Furthermore, compared with a state‐of‐the‐art inexact floating‐point adder, the proposed method provides an improvement of 7% and 21% in terms of the power consumption and delay. In addition, the proposed floating‐point adder has been investigated in terms of error, and the mean error of the proposed floating‐point adder at worst is about 55% less than that of another approximate floating‐point adder considered in this work. High dynamic range (HDR) images are processed using the proposed approximate floating‐point adders to show the performance of the proposed adder. The results show that, on average, peak signal‐to‐noise ratio increased by 9.6 and 18.64 dB, which may be achieved by utilizing the proposed floating‐point adder.
Analysis of alert message propagation on the highway in VANET assuming Markovian vehicle arrival process
Authors: Mahmood Dhari Ali , Horvath Gabor 
Published: June 2020

SummaryVehicular ad hoc networks (VANETs) provide the infrastructure for the intelligent transportation system (ITS). The number of vehicles that are capable of communicating with each other through VANET is increasing. In this paper, we provide several analytical results regarding the message propagation on the highway in VANET. In our scenario, there is a stationary message source (i.e., alert messages are generated at an accident). Vehicles can receive the message and get informed when they reach the radio transmission range of the message source or another informed vehicle. Most papers published on the analysis of message propagation assume that the inter arrival times between vehicles follow a Poisson process; there are very few results available with more general traffic model. In this paper, we show that the Poisson process is not always suitable for modeling vehicle traffic. Instead of the Poisson process, we propose to use the more general Markovian arrival process (MAP) to model the vehicle headway times and derive the probability that the message propagates beyond a certain distance from the accident under this traffic assumption. Through several numerical examples, we demonstrate how much the statistics of the vehicle arrival process impacts the message propagation distance.
Cytomorphology of Mycobacterium avium intracellulare‐associated ascites
Authors: Satturwar Swati , Pantanowitz Liron , Xing Juan , Schoedel Karen , Weber David , Monaco Sara E. 
Published: June 2020

AbstractAscites due to Mycobacterium avium intracellulare (MAI) infection is extremely rare and associated with a poor outcome. The cytomorphology of this condition has not been previously reported. We present a unique case of a 45‐year‐old woman with iatrogenic immunodeficiency who developed MAI‐associated chylous ascites. The ascitic fluid cytology showed numerous lymphocytes and foamy histiocytes with abundant intracytoplasmic MAI organisms. The diagnosis was confirmed by tissue biopsy showing MAI mesenteritis. It is important to consider MAI‐associated ascites in the differential diagnosis whenever ascitic fluid shows a predominant population of lymphocytes and macrophages, especially in immunocompromised patients.
Association between circulating follistatin‐like‐1 and metabolic syndrome in middle‐aged and old population: A cross‐sectional study
Authors: Yang Shan , Dai Han , Hu Wenjing , Geng Shan , Li Ling , Li Xinrun , Liu Hua , Liu Dongfang , Li Ke , Yang Gangyi , Yang Mengliu 
Published: June 2020

AbstractAimFollistatin‐like‐1 (FSTL‐1) is considered to be a novel cytokine, and it is associated with metabolic diseases. However, it is necessary to investigate further the association of FSTL‐1 with metabolic syndrome (MetS) and insulin resistance (IR). We performed a cross‐sectional study to investigate the associated of circulating FSTL‐1 with the MetS.Materials and methodsA cross‐sectional study was performed in 487 Chinese people, including 231 control subjects and 256 patients with MetS. Bioinformatics analysis was used to determine the protein and pathways associated with FSTL‐1. The protein and protein interaction (PPI) network was constructed and analysed. Serum FSTL‐1 concentrations were determined by an ELISA assay. The association of FSTL‐1 with MetS components and IR was assessed.ResultsSerum FSTL‐1 levels were markedly higher in patients with newly diagnosed MetS than in controls (7.5 [5.6‐9.2] vs 5.8 [5.0‐7.7] μg/L, P < .01). According to bioinformatics analysis, the top high‐degree genes were identified as the core genes, including SPARCL1, CYR61, LTBP1, IL‐6, BMP2, BMP4, FBN1, FN1 CHRDL1 and FSTL‐3. These genes are mainly enriched in pathways including TGF‐ß, AGE‐RAGE signalling pathway in diabetic complications, and Hippo signalling pathways; in basal cell carcinoma, cytokine‐cytokine receptor interaction and in amoebic and Yersinia infections. Furthermore, serum FSTL‐1 levels were positively associated with fasting plasma glucose (FPG), waist circumference (WC), blood pressure, triglyceride levels and visceral adiposity index (VAI). We found that serum FSTL‐1 levels were markedly associated with MetS and IR by binary logistic regression analysis.ConclusionsWe conclude that FSTL‐1 may be a novel cytokine related to MetS and IR.
Hydroxychloroquine, COVID‐19 and diabetes. Why it is a different story
Authors: Stoian Anca Pantea , Catrinoiu Doina , Rizzo Manfredi , Ceriello Antonio 
Published: June 2020

AbstractHydroxychloroquine has been proposed for the cure of the COVID‐19 due to its anti‐inflammatory and anti‐viral action. People with diabetes are more prone to severe outcome if affected by COVID‐19 and the use of Hydroxychloroquine might have some benefit in this setting. However, the use of Hydroxychloroquine in diabetes deserves particular attention for its documented hypoglycemic action.
Application of a chiral high‐performance liquid chromatography‐tandem mass spectrometry method for the determination of 13 related amphetamine‐type stimulants to forensic samples: Interpretative hypotheses
Authors: Schwelm Hannes M. , Grumann Christina , Auwärter Volker , Neukamm Merja A. 
Published: June 2020

AbstractInterpretation of amphetamine‐type stimulant (ATS) findings in urine samples can be challenging without chiral information. We present a sensitive enantioselective high‐performance liquid chromatography–tandem mass spectrometry method for the quantification of (R)‐amphetamine, (S)‐amphetamine, (R)‐methamphetamine, (S)‐methamphetamine, (1R,2R)‐pseudoephedrine, (1S,2S)‐pseudoephedrine, (1R,2S)‐ephedrine, (1S,2R)‐ephedrine, (1R,2S)‐norephedrine, (1S,2R)‐norephedrine, (R)‐cathinone, (S)‐cathinone, and (1S,2S)‐norpseudoephedrine (cathine) in urine. The method was successfully applied to more than 100 authentic urine samples from forensic casework. In addition, samples from a controlled self‐administration of (1S,2S)‐pseudoephedrine (Rinoral, 1200 mg within 6 days) were analyzed. The results strengthen the hypothesis that (1R,2S)‐norephedrine is a minor metabolite of amphetamine and methamphetamine. We suggest cathine and (1S,2R)‐norephedrine as minor metabolites of amphetamine racemate in humans. Small methamphetamine concentrations detected in samples with high concentrations of amphetamine could result from a metabolic formation by methylation of amphetamine although in samples with an (R)/(S) ratio for methamphetamine < 1 an additional (previous) (S)‐methamphetamine consumption seems likely. Our data suggest that even amphetamine concentrations exceeding methamphetamine concentrations in urine can be caused by the biotransformation of methamphetamine to amphetamine as long as no (R)‐amphetamine is detected. However, without chiral information, such findings might be (falsely) assumed as a co‐consumption of both substances. Cathinone enantiomers detected in urine samples with high amphetamine concentrations can be interpreted as metabolites of amphetamine. In addition, the results of the self‐administration study revealed that both cathinone enantiomers are minor metabolites of (1S,2S)‐pseudoephedrine, which is the active ingredient of various medicines used for cold. The enantioselective analysis is a powerful tool to avoid the misinterpretation of ATS findings in urine samples.
Acknowledging uncertainty in evolutionary reconstructions of ecological niches
Authors: Owens Hannah L. , Ribeiro Vivian , Saupe Erin E. , Cobos Marlon E. , Hosner Peter A. , Cooper Jacob C. , Samy Abdallah M. , Barve Vijay , Barve Narayani , Muñoz‐R. Carlos J. , Peterson A. Townsend 
Published: June 2020

AbstractReconstructing ecological niche evolution can provide insight into the biogeography and diversification of evolving lineages. However, comparative phylogenetic methods may infer the history of ecological niche evolution inaccurately because (a) species' niches are often poorly characterized; and (b) phylogenetic comparative methods rely on niche summary statistics rather than full estimates of species' environmental tolerances. Here, we propose a new framework for coding ecological niches and reconstructing their evolution that explicitly acknowledges and incorporates the uncertainty introduced by incomplete niche characterization. Then, we modify existing ancestral state inference methods to leverage full estimates of environmental tolerances. We provide a worked empirical example of our method, investigating ecological niche evolution in the New World orioles (Aves: Passeriformes: Icterus spp.). Temperature and precipitation tolerances were generally broad and conserved among orioles, with niche reduction and specialization limited to a few terminal branches. Tools for performing these reconstructions are available in a new R package called nichevol.
Western bumble bee: declines in the continental United States and range‐wide information gaps
Authors: Graves Tabitha A. , Janousek William M. , Gaulke Sarah M. , Nicholas Amy C. , Keinath Douglas A. , Bell Christine M. , Cannings Syd , Hatfield Richard G. , Heron Jennifer M. , Koch Jonathan B. , Loffland Helen L. , Richardson Leif L. , Rohde Ashley T. , Rykken Jessica , Strange James P. , Tronstad Lusha M. , Sheffield Cory S. 
Published: June 2020

AbstractIn recent decades, many bumble bee species have declined due to changes in habitat, climate, and pressures from pathogens, pesticides, and introduced species. The western bumble bee (Bombus occidentalis), once common throughout western North America, is a species of concern and will be considered for listing by the U.S. Fish and Wildlife Service (USFWS) under the Endangered Species Act (ESA). We attempt to improve alignment of data collection and research with USFWS needs to consider redundancy, resiliency, and representation in the upcoming species status assessment. We reviewed existing data and literature on B. occidentalis, highlighting information gaps and priority topics for research. Priorities include increased knowledge of trends, basic information on several life‐history stages, and improved understanding of the relative and interacting effects of stressors on population trends, especially the effects of pathogens, pesticides, climate change, and habitat loss. An understanding of how and where geographic range extent has changed for the two subspecies of B. occidentalis is also needed. We outline data that could be easily collected in other research projects that would increase their utility for understanding range‐wide trends of bumble bees. We modeled the overall trend in occupancy from 1998 to 2018 of Bombus occidentalis within the continental United States using existing data. The probability of local occupancy declined by 93% over 21 yr from 0.81 (95% CRI = 0.43, 0.98) in 1998 to 0.06 (95% CRI = 0.02, 0.16) in 2018. The decline in occupancy varied spatially by landcover and other environmental factors. Detection rates vary in both space and time, but peak detection across the continental United States occurs in mid‐July. We found considerable spatial gaps in recent sampling, with limited sampling in many regions, including most of Alaska, northwestern Canada, and the southwestern United States. We therefore propose a sampling design to address these gaps to best inform the ESA species status assessment through improved assessment of how the spatial distribution of stressors influences occupancy changes. Finally, we request involvement via data sharing, participation in occupancy sampling with repeated visits to distributed survey sites, and complementary research to address priorities outlined in this paper.