bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Interleukin‐1 Receptor–Associated Kinase 4 Inhibitor PF‐06650833 Blocks Inflammation in Preclinical Models of Rheumatic Disease and in Humans Enrolled in a Randomized Clinical Trial
Authors: Winkler Aaron , Sun Weiyong , De Saurav , Jiao Aiping , Sharif M. Nusrat , Symanowicz Peter T. , Athale Shruti , Shin Julia H. , Wang Ju , Jacobson Bruce A. , Ramsey Simeon J. , Dower Ken , Andreyeva Tatyana , Liu Heng , Hegen Martin , Homer Bruce L. , Brodfuehrer Joanne , Tilley Mera , Gilbert Steven A. , Danto Spencer I. , Beebe Jean J. , Barnes Betsy J. , Pascual Virginia , Lin Lih‐Ling , Kilty Iain , Fleming Margaret , Rao Vikram R. 
Published: August 2021

ObjectiveTo investigate the role of PF‐06650833, a highly potent and selective small‐molecule inhibitor of interleukin‐1–associated kinase 4 (IRAK4), in autoimmune pathophysiology in vitro, in vivo, and in the clinical setting.MethodsRheumatoid arthritis (RA) inflammatory pathophysiology was modeled in vitro through 1) stimulation of primary human macrophages with anti–citrullinated protein antibody immune complexes (ICs), 2) RA fibroblast‐like synoviocyte (FLS) cultures stimulated with Toll‐like receptor (TLR) ligands, as well as 3) additional human primary cell cocultures exposed to inflammatory stimuli. Systemic lupus erythematosus (SLE) pathophysiology was simulated in human neutrophils, dendritic cells, B cells, and peripheral blood mononuclear cells stimulated with TLR ligands and SLE patient ICs. PF‐06650833 was evaluated in vivo in the rat collagen‐induced arthritis (CIA) model and the mouse pristane‐induced and MRL/lpr models of lupus. Finally, RNA sequencing data generated with whole blood samples from a phase I multiple‐ascending‐dose clinical trial of PF‐06650833 were used to test in vivo human pharmacology.ResultsIn vitro, PF‐06650833 inhibited human primary cell inflammatory responses to physiologically relevant stimuli generated with RA and SLE patient plasma. In vivo, PF‐06650833 reduced circulating autoantibody levels in the pristane‐induced and MRL/lpr murine models of lupus and protected against CIA in rats. In a phase I clinical trial (NCT02485769), PF‐06650833 demonstrated in vivo pharmacologic action pertinent to SLE by reducing whole blood interferon gene signature expression in healthy volunteers.ConclusionThese data demonstrate that inhibition of IRAK4 kinase activity can reduce levels of inflammation markers in humans and provide confidence in the rationale for clinical development of IRAK4 inhibitors for rheumatologic indications.
Measuring the citation context of national self‐references
Authors: Chen Liyue , Ding Jielan , Larivière Vincent 
Published: August 2021

AbstractThe emphasis on research evaluation has brought scrutiny to the role of self‐citations in the scholarly communication process. While author self‐citations have been studied at length, little is known on national‐level self‐references (SRs). This paper analyses the citation context of national SRs, using the full‐text of 184,859 papers published in PLOS journals. It investigates the differences between national SRs and nonself‐references (NSRs) in terms of their in‐text mention, presence in enumerations, and location features. For all countries, national SRs exhibit a higher level of engagement than NSRs. NSRs are more often found in enumerative citances than SRs, which suggests that researchers pay more attention to domestic than foreign studies. There are more mentions of national research in the methods section, which provides evidence that methodologies developed in a nation are more likely to be used by other researchers from the same nation. Publications from the United States are cited at a higher rate in each of the sections, indicating that the country still maintains a dominant position in science. On the whole, this paper contributes to a better understanding of the role of national SRs in the scholarly communication system, and how it varies across countries and over time.
Radical Cyclization of 1,n‐Enynes and 1,n‐Dienes for the Synthesis of 2‐Pyrrolidone
Authors: Jiang Li‐Lin , Hu Sen‐Jie , Xu Qing , Zheng Hongxing , Wei Wen‐Ting 
Published: August 2021

Abstract2‐Pyrrolidones have aroused enormous interest as a useful structural moiety in drug discovery; however, not only does their syntheses suffer from low selectivity and yield, but also it requires high catalyst loadings. The radical cyclization of 1,n‐enynes and 1,n‐dienes has demonstrated to be an attractive method for the synthesis of 2‐pyrrolidones due to its mild reaction conditions, fewer steps, higher atom economy, excellent functional group compatibility, and high regioselectivity. Furthermore, radical receptors with unsaturated bonds (i. e. 1,n‐enynes and 1,n‐dienes) play a crucial role in realizing radical cyclization because of the ability to selectively introduce one or more radical sources. In this review, we discuss representative examples of methods involving the radical cyclization of 1,n‐enynes and 1,n‐dienes published in the last five years and discuss each prominent reaction design and mechanism, providing favorable tools for the synthesis of valuable 2‐pyrrolidone for a variety of applications.
K2Na3[{B6O10(OH)}{B3O4(OH)3}] ⋅ H2O: A Layered Borate Built by Mixed Oxoboron Clusters with Nonlinear‐Optical Property
Authors: Chen Chong‐An , Qiu Qi‐Ming , Yang Guo‐Yu 
Published: August 2021

AbstractA new acentric borate, K2Na3[{B6O10(OH)}‐{B3O4(OH)3}] ⋅ H2O (1) has been made under solvothermal condition. 1 has layered structure made by B6O13(OH)‐based chains and B3O5(OH)3‐bridging clusters. Second‐harmonic generation (SHG) measurements reveal that 1 is a phase‐matchable nonlinear optical (NLO) material, showing the SHG signal intensity of 1.8 times that of KDP (KH2PO4). Besides, UV‐Vis diffuse reflectance spectrum shows that 1 has the short deep UV (DUV) absorption cutoff edge of 198 nm. Thermogravimetric analysis reveals it has good thermal stability. Also 1 represents firstly mixed oxoboron clusters‐made 2D layered borate with NLO property.
Optimal interpregnancy interval in autism spectrum disorder: A multi‐national study of a modifiable risk factor
Authors: Pereira Gavin , Francis Richard W. , Gissler Mika , Hansen Stefan N. , Kodesh Arad , Leonard Helen , Levine Stephen Z. , Mitter Vera R. , Parner Eric T. , Regan Annette K. , Reichenberg Abraham , Sandin Sven , Suominen Auli , Schendel Diana 
Published: August 2021

AbstractIt is biologically plausible that risk of autism spectrum disorder (ASD) is elevated by both short and long interpregnancy intervals (IPI). We conducted a retrospective cohort study of singleton, non‐nulliparous live births, 1998–2007 in Denmark, Finland, and Sweden (N = 925,523 births). Optimal IPI was defined as the IPI at which minimum risk was observed. Generalized additive models were used to estimate relative risks (RR) of ASD and 95% Confidence Intervals (CI). Population impact fractions (PIF) for ASD were estimated under scenarios for shifts in the IPI distribution. We observed that the association between ASD (N = 9302) and IPI was U‐shaped for all countries. ASD risk was lowest (optimal IPI) at 35 months for all countries combined, and at 30, 33, and 39 months in Denmark, Finland, and Sweden, respectively. Fully adjusted RRs at IPIs of 6, 12, and 60 months were 1.41 (95% CI: 1.08, 1.85), 1.26 (95% CI: 1.02, 1.56), and 1.24 (95% CI: 0.98, 1.58) compared to an IPI of 35 months. Under the most conservative scenario PIFs ranged from 5% (95% CI: 1%–8%) in Denmark to 9% (95% CI: 6%–12%) in Sweden. The minimum ASD risk followed IPIs of 30–39 months across three countries. These results reflect both direct IPI effects and other, closely related social and biological pathways. If our results reflect biologically causal effects, increasing optimal IPIs and reducing their indications, such as unintended pregnancy and delayed age at first pregnancy has the potential to prevent a salient proportion of ASD cases.Lay SummaryWaiting 35 months to conceive again after giving birth resulted in the least risk of autism. Shorter and longer intervals resulted in risks that were up to 50% and 85% higher, respectively. About 5% to 9% of autism cases might be avoided by optimizing birth spacing.
Optimization, extraction, and purification of three bioactive compounds from Entada phaseoloides by high‐speed countercurrent chromatography
Authors: Zhou Yan , Shan Hu , Lü Haitao 
Published: August 2021

AbstractThe objective of this paper was to develop a preparative method for the separation and purification of phaseoloidin, entadamide A, and entadamide A‐β‐D‐glucopyranoside from the crude extract of Entada phaseoloides by high‐speed countercurrent chromatography (HSCCC) for the first time. Optimized by orthogonal experiments, the extraction conditions were extraction temperature of 65°C, solid‐to‐liquid ratio of 1:15 (g/mL), ethanol concentration of 40%, and extraction time of 2.5 h. Using n‐butanol‐acetic acid‐water (4:1:5, v/v/v) as the two‐phase solvent system, 38.79 mg phaseoloidin (the purity was 99.3% with a recovery of 98.1%), 34.85 mg entadamide A (the purity was 96.4% with a recovery of 98.5%), and 33.97 mg entadamide A‐β‐D‐glucopyranoside (the purity was 98.6% with a recovery of 97.7%) were obtained from 500 mg crude extract by HSCCC in head‐to‐tail elution mode. The retention ratio of stationary phase was 51.0%. According to the antioxidant activity assays, phaseoloidin, entadamide A, and entadamide A‐β‐D‐glucopyranoside had certain scavenging abilities on 1,1‐diphenyl‐2‐picrylhydrazyl free radicals and hydroxyl free radicals.
The safety and efficacy of botulinum toxin A on the treatment of depression
Authors: Zhang Qilin , Wu Wenqi , Fan Yuxin , Li Yang , Liu Jing , Xu Yingying , Jiang Caixia , Tang Zhen , Cao Cong , Liu Tong , Chen Li‐Hua , Hu Hua , Luo Weifeng 
Published: August 2021

AbstractObjectivesEffective strategy for the treatment of depression is limited. This study was to evaluate the safety and efficacy of botulinum toxin A (BoNT/A) in the treatment of depression.MethodsSeventy‐six patients were assigned to the BoNT/A group (n = 52) and sertraline control group (n = 24). For the BoNT/A group, BoNT/A was injected into the frowning muscle, depressor muscle, occipital frontalis muscle, lateral canthus, and bilateral temporal region at 20 sites. Five units per site and a total of 100 units of BoNT/A were given. Patients in the sertraline control group were medicated with sertraline 50–200 mg (114.58 ± 52.08 mg) per day. Depression was assessed by the 17‐item Hamilton Depression Scale (HAMD‐17), 14‐item Hamilton Anxiety Scale (HAMA‐14), Self‐rating Depression Scale (SDS), and Self‐rating Anxiety Scale (SAS). All participants were followed up for 12 weeks.ResultsScores of HAMD, HAMA, SDS, and SAS decreased significantly in both BoNT/A and sertraline groups after treatment for 12 weeks. Overall, there were no differences in decreased magnitude between the two groups (p > .05). The HAMA, SDS, and SAS results showed that the onset time of BoNT/A was earlier than that of sertraline. Side effects rates were 15.38% for BoNT/A and 33.33% for sertraline.ConclusionThis study demonstrated significant antidepressant effects of BoNT/A. The efficacy of BoNT/A was comparable with established antidepressant sertraline. The onset time of BoNT/A was earlier than sertraline, and the proportion of side effects was less than sertraline. Therefore, BoNT/A could be a safe and effective option for the treatment of depression.
Strategic ambidexterity in green product innovation: Obstacles and implications
Authors: Peters Kristian , Buijs Paul 
Published: August 2021

AbstractScholars and managers routinely point to various uncertainties in explaining why manufacturing firms struggle with green product innovation and why green product innovation is different from conventional product innovation. This explanation is yet unsatisfactory as a thorough understanding of how a firm deals with uncertainty exists in conventional innovation literature. At the same time, there is a lack of agreement and understanding how a firm's capabilities shape its green product innovation practices, which could contribute to this gap. Based on a case study at five multinational manufacturers, this paper sets out to contribute to the capability perspective on green product innovation by understanding how manufacturing firms learn and innovate in order to make and sell greener products. A powerful and favored way for firms to learn and innovate under uncertainty is through strategic ambidexterity. With this learning strategy, firms rely on existing competences in one area (exploitation) while they simultaneously explore new competences in another area (exploration). However, our results show that strategic ambidexterity is oftentimes unachievable due to several factors, and as result, firms are forced to choose between a highly uncertain and risky alternative strategy and a more conservative but also less green strategy based on exploitation only, which is often the preferred option. In addition, our findings shed a new light on the role of uncertainty in green product innovation as we conclude that uncertainties firms face in green product innovation are indeed abundant, but are fundamentally not new nor caused by external sources only.
Study on the Composition and Physiological Activity of the Essential Oils and Extracts of Cinnamomum camphora Fruit
Authors: Lv Chenyuan , Hao Linyu , Cui Xinang , Yi Fengping , Su Chang 
Published: August 2021

AbstractSupercritical carbon dioxide (SC‐CO2), hydrodistillation (HDO), ethanol extraction (EE), and petroleum ether extraction (PE) were used to extract the essential oil and extracts of Cinnamomum camphora fruit in this study. Gas chromatography‐mass spectrometry was used to identify the volatile components of essential oils and extracts, and 63 compounds were identified. 2,2‐Diphenyl‐1‐picrylhydrazyl (DPPH) and 2,2′‐azinobis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS) radical scavenging assay and Ferric reducing ability of plasma (FRAP) assays and the inhibition experiment of bacteria and fungi (Staphylococcus aureus (S. aureus), Hay bacillus (H. bacillus), Escherichia coli (E. coli), Aspergillus niger (A. niger), Candida albicans (C. albicans)) showed these essential oils and extracts indicated antioxidant and antibacterial activities. S. aureus was the most sensitive to the essential oil (MIC=0.08 mg/ml). Combined with the Brine Shrimp Lethality Test (BSLT) experiment, HDO (LD50=68.21 μg/ml) was considered to have the most potential natural preservative. Subsequently, the inhibitory mechanism of HDO on bacteria and fungi was explored through extracellular conductivity and SEM, and the possibility of HDO to preserve the freshness of bananas was verified through banana shelf‐life experiments. The results suggested these essential oils and extracts of Cinnamomum camphora fruit indicated effectively inhibit the growth of microorganisms on the surface of bananas, extend the shelf‐life, and have the potential to become a natural antiseptic ingredient.
Simultaneous separation of atenolol enantiomers and its acid/alkaline degradation impurities on mixed‐mode chiral ligand exchange stationary phases
Authors: Bai Hui , Chen Lei 
Published: August 2021

AbstractSimultaneous separation of the enantiomer and impurities is a huge challenge for the quality control of the chiral drug. In this work, mixed‐mode chiral ligand exchange stationary phases (CSPs) modified by octyl and sulfhydryl ligands were prepared by vapor deposition and click chemistry methods. Qualitative and quantitative determination of the prepared CSPs were achieved by Fourier transform infrared spectroscopy, solid‐state 13C CP/MAS NMR, and elemental analysis. The chiral resolution of CSPs was investigated through a comprehensively chromatographic evaluation of various racemates. Besides, the thermodynamic experiment was carried out to elucidate the contribution of hydrophobic ligand to the improvement of chiral recognition and selectivity. Atenolol and its degradation products were analyzed on the synthesized CSPs and compared with the commercial chiral column. A good separation of atenolol enantiomers from its acid and alkaline degradation impurities was simultaneously achieved on the C8/L‐Hypro CSP. This new CSP is expected to have more applications in the quality control of other chiral drugs.
Accelerating high‐order stencils on GPUs
Authors: Sai Ryuichi , Mellor‐Crummey John , Meng Xiaozhu , Zhou Keren , Araya‐Polo Mauricio , Meng Jie 
Published: August 2021

SummaryFinite‐difference methods based on high‐order stencils are commonly used for modeling of seismic wave propagation, weather forecasting, computational fluid dynamics, convolutional neural networks, and others. Nowadays, the community commonly employs graphics processing units (GPUs) to accelerate such stencil computations. As a result, knowing how to write efficient stencil computations for GPUs is of significant interest. While high‐performance, low‐order stencils on GPUs have been studied extensively in the literature, not all proposed approaches work well for high‐order stencils. Furthermore, coping with boundary conditions used with stencils for seismic modeling makes it challenging to efficiently exploit thread‐level parallelism on GPUs. In this article, we describe several implementations of a 25‐point stencil. We evaluate our stencil code shapes, memory hierarchy usage, data access patterns, and other performance attributes on several modern GPUs and compare them with machine rooflines. On average, our top‐performing kernels achieve six times the performance of a 25‐point stencil code developed in C and mapped to GPUs using OpenACC. Several of our implementations have excellent performance portability across multiple generations of both NVIDIA and AMD GPUs.
Metal‐Organic‐Framework Based Functional Materials for Uranium Recovery: Performance Optimization and Structure/Functionality‐Activity Relationships
Authors: Zhao Zhiwei , Cheng Gong , Zhang Yizhe , Han Bing , Wang Xiangke 
Published: August 2021

AbstractUranium recovery has profound significance in both uranium resource acquisition and pollution treatment. In recent years, metal‐organic frameworks (MOFs) have attracted much attention as potential uranium adsorbents owing to their tunable structural topology and designable functionalities. This review explores the research progress in representative classic MOFs (MIL‐101, UiO‐66, ZIF‐8/ZIF‐67) and other advanced MOF‐based materials for efficient uranium extraction in aqueous or seawater environments. The uranium uptake mechanism of the MOF‐based materials is refined, and the structure/functionality‐property relationship is further systematically elucidated. By summarizing the typical functionalization and structure design methods, the performance improvement strategies for MOF‐based adsorbents are emphasized. Finally, the present challenges and potential opportunities are proposed for the breakthrough of high‐performance MOF‐based materials in uranium extraction.
Longitudinal Data Discontinuity in Electronic Health Records and Consequences for Medication Effectiveness Studies
Authors: Joshua Lin Kueiyu , Jin Yinzhu , Gagne Joshua , Glynn Robert J. , Murphy Shawn N. , Tong Angela , Schneeweiss Sebastian 
Published: August 2021

Electronic health record (EHR) discontinuity (i.e., receiving care outside of the study EHR system), can lead to information bias in EHR‐based real‐world evidence (RWE) studies. An algorithm has been previously developed to identify patients with high EHR‐continuity. We sought to assess whether applying this algorithm to patient selection for inclusion can reduce bias caused by data‐discontinuity in four RWE examples. Among Medicare beneficiaries aged >=65 years from 2007 to 2014, we established 4 cohorts assessing drug effects on short‐term or long‐term outcomes, respectively. We linked claims data with two US EHR systems and calculated %bias of the multivariable‐adjusted effect estimates based on only EHR vs. linked EHR‐claims data because the linked data capture medical information recorded outside of the study EHR. Our study cohort included 77,288 patients in system 1 and 60,309 in system 2. We found the subcohort in the lowest quartile of EHR‐continuity captured 72–81% of the short‐term and only 21–31% of the long‐term outcome events, leading to %bias of 6–99% for the short‐term and 62–112% for the long‐term outcome examples. This trend appeared to be more pronounced in the example using a nonuser comparison rather than an active comparison. We did not find significant treatment effect heterogeneity by EHR‐continuity for most subgroups across empirical examples. In EHR‐based RWE studies, investigators may consider excluding patients with low algorithm‐predicted EHR‐continuity as the EHR data capture relatively few of their actual outcomes, and treatment effect estimates in these patients may be unreliable.
Enhanced collision resolution and throughput analysis for the 802.11 distributed coordination function
Authors: Kobbaey Thaeer , Hamzaoui Raouf , Ahmad Shakeel , Al‐Fayoumi Mustafa , Thomos Nikolaos 
Published: August 2021

SummaryThe IEEE 802 standards rely on the distributed coordination function (DCF) as the fundamental medium access control method. DCF uses the binary exponential backoff (BEB) algorithm to regulate channel access. The backoff time determined by BEB depends on a contention window (CW) whose size is doubled if a station suffers a collision and reset to its minimum value after a successful transmission. Doubling the size of CW reduces channel access time, which decreases the throughput. Resetting it to its minimum value harms fairness since the station will have a better chance of accessing the channel compared to stations that suffered a collision. We propose an algorithm that addresses collisions without instantly increasing the CW size. Our algorithm aims to reduce the collision probability without affecting the channel access time and delay. We present extensive simulations for fixed and mobile scenarios. The results show that, on average, our algorithm outperforms BEB in terms of throughput and fairness. Compared to exponential increase exponential decrease (EIED), our algorithm improves, on average, throughput and delay performance. We also propose analytical models for BEB, EIED and our algorithm. Our models extend Bianchi's popular Markov chain‐based model by using a collision probability that is dependent on the station transmission history. Our models provide a better estimation of the probability that a station transmits in a random slot time, which allows a more accurate throughput analysis. Using our models, we show that both the saturation throughput and maximum throughput of our algorithm are higher than those of BEB and EIED.
Cloning capacity helps seeds of Garcinia xanthochymus counter animal predation
Authors: Wang Zhen‐yu , Cao Lin , Yan Chuan , Niu Yu‐da , Chong Kang , Zhang Zhi‐bin 
Published: August 2021

AbstractSeed predators have the potential to act as agents of natural selection that influence seed traits and seed fates, which in turn affect the whole plant population dynamic. Accordingly, plants deploy a variety of mechanisms (e.g., resistance and tolerance strategies) to lessen the impact of predation on seed crop or on an individual seed. In this study, we described a novel mechanism, seed cloning strategy, in a tropical plant species in countering animal predation. By conducting field‐ and laboratory‐based germination experiments, we found that both rodent damaged and artificially damaged seed fragments of a large‐seeded tree Garcinia xanthochymus (Clusiaceae) could successfully germinate and establish as seedlings. Tissue culture experiments revealed that G. xanthochymus has no endosperm in seeds, and its seed fragments own strong capacity of differentiation and cloning. Seed damage negatively affected seedling growth and germination, but the seed germination rate was remarkably high. Our study suggests that, seed cloning capacity, adopted by the large‐seeded tree G. xanthochymus may act as a novel strategy counteract for seed predation and would play a significant role in stabilizing the mutualism between plant and animals.