bluuebunny/crossref_metadata_2025_split huggingface dataset:
GLPG1205, a GPR84 Modulator: Safety, Pharmacokinetics, and Pharmacodynamics in Healthy Subjects
Authors: Timmis Helen , Van Kaem Tim , Desrivot Julie , Dupont Sonia , Meuleners Luc , Beetens Johan , Helmer Eric , Santermans Eva , Huettner Silke 
Published: May 2021

AbstractGLPG1205 is a modulator of GPR84, a G‐protein–coupled receptor reported to be associated with several diseases. Safety, tolerability, pharmacokinetics, and pharmacodynamics of GLPG1205 in healthy subjects were evaluated in 2 randomized, double‐blind, placebo‐controlled, single‐site, phase 1 studies. In study 1, 16 (aged 21‐48 years) and 24 (24‐50 years) healthy men received single doses of GLPG1205 10 to 800 mg, and GLPG1205 50, 100, or 200 mg once daily for 14 days, respectively, or placebo. Study 2 evaluated the effect of aging on GLPG1205 pharmacokinetics: 24 healthy men (aged 37–83 years), weight‐matched into 3 age cohorts (65‐74, ≥75, and 18‐50 years), received GLPG1205 50 mg or placebo once daily for 14 days; an open‐label part of this study evaluated a GLPG1205 250‐mg loading dose followed by 50 mg once daily for 13 days in 8 healthy men (aged 68‐74 years). Single (up to 800 mg) and multiple (maximum tolerated dose 100 mg once daily) GLPG1205 doses had favorable safety and tolerability profiles. After single administration of GLPG1205, median time to occurrence of maximum observed plasma concentration and arithmetic mean apparent terminal half‐life ranged from 2.0 to 4.0 and from 30.1 to 140 hours, respectively. Age did not affect GLPG1205 exposure. GPR84 receptor occupancy with GLPG1205 vs placebo confirmed target engagement. These results support further clinical development of GLPG1205.
Performance characterization of video analytics workloads in heterogeneous edge infrastructures
Authors: Rivas Daniel , Guim Francesc , Polo Jordà , Carrera David 
Published: May 2021

SummaryPowered by deep learning, video analytic applications process millions of camera feeds in real‐time to extract meaningful information from their surroundings. And this number grows by the minute. To avoid saturating the backhaul network and provide lower latencies, a distributed and heterogeneous edge cloud is postulated as a key enabler for widespread video analytics. This article provides a complete characterization of end‐to‐end video analytics across a set of hardware platforms and different neural network architectures. Each platform is selected to fill a different gap in a distributed, shared, and heterogeneous infrastructure. Moreover, we analyze how performance scales on each of these platforms with respect to the amount of resources dedicated to video analytics. Finally, we extract the key conclusions of the characterization to build an experimental model to estimate performance and cost of end‐to‐end video analytics in different edge scenarios. Our experiments show that managing video analytics workloads efficiently requires awareness of both, the platforms in which these are executed, and the full end‐to‐end pipeline. To the best of our knowledge, this is the first work that provides a complete characterization of end‐to‐end video analytics in heterogeneous edge platforms.
Edge intelligence‐enabled supply chain financial model based on Business‐to‐Business e‐business platforms
Authors: Yin Feng , Yang Rongjun , Yu Hongxin , Zhou Wei , Zhao Yuanjun , Zhang Shuai 
Published: May 2021

SummaryBased on the analysis of the existing traditional supply chain financial model, this article proposes an edge intelligence‐enabled supply chain financial model based on Business‐to‐Business (B2B) platforms, combines the operation mechanism of the model and the quantitative analysis thinking of the traditional supply chain financing. This article uses the model to construct and evaluates the cost–benefit model of dealers, manufacturers, and B2B e‐business platforms in the perspective of the supply chain finance for B2B platforms. In order to further explore the operation strategy of supply chain member enterprises, this article also explores the selection of financing objects of B2B platforms, the optimization of financing cost rate formulated by the loan amount of financing enterprises, and the optimization of product order quantity. Numerical analysis shows that the proposed model can directly reflect the changing trend of the relevant parameters of B2B platforms' supply chain financial model and provide suggestions for the cooperation mechanism between supply chain and commercial banks.
Discovery of Nonracemic Amisulpride to Maximize Benefit/Risk of 5‐HT7 and D2 Receptor Antagonism for the Treatment of Mood Disorders
Authors: Hopkins Seth C. , Wilkinson Scott , Corriveau Taryn J. , Nishikawa Hiroyuki , Nakamichi Keiko , Loebel Antony , Koblan Kenneth S. 
Published: May 2021

In contrast to the dose‐occupancy relationship in the treatment of schizophrenia, the minimal effective level of dopamine receptor 2 (D2R) blockade for antipsychotics in the treatment of bipolar depression is unknown. Lower doses aimed at reducing extrapyramidal side effects must be balanced against the need to retain the therapeutic benefit of D2R blockade on emergent cycling, mixed, manic, anxiety, and/or psychotic symptoms. Dose‐reductions intended to lower D2R blockade, however, could also decrease concomitant serotonin receptor antagonism and its potential benefit on depressive symptoms. Here, we uncoupled the potential antidepressant activity in amisulpride, driven by 5‐HT7 receptor (5‐HT7R) antagonism, from the D2R‐mediated antipsychotic activity by discovering that each enantiomer favors a different receptor. Aramisulpride was more potent at 5‐HT7R relative to esamisulpride (Ki 47 vs. 1,900 nM, respectively), whereas esamisulpride was more potent at D2R (4.0 vs. 140 nM). We hypothesized that a nonracemic ratio might achieve greater 5‐HT7R‐mediated antidepressant effects at a lower level of D2R blockade. The dose‐occupancy relationship of esamisulpride at D2R was determined by positron emission tomography (PET) imaging in human volunteers. Separately the dose‐relationship of aramisulpride was established in humans using suppression of rapid eye movement (REM) sleep as a marker of 5‐HT7R antagonism. These results led to the discovery of an 85:15 ratio of aramisulpride to esamisulpride (SEP‐4199) that maximizes the potential for antidepressant benefit of aramisulpride via 5‐HT7R and reduces esamisulpride to minimize D2R‐related extrapyramidal side effects while still retaining D2R‐mediated effects predicted to provide benefit in bipolar depression. The antidepressant efficacy of SEP‐4199 was recently confirmed in a proof‐of‐concept trial for the treatment of bipolar depression (NCT03543410).
Learned Embeddings from Deep Learning to Visualize and Predict Protein Sets
Authors: Dallago Christian , Schütze Konstantin , Heinzinger Michael , Olenyi Tobias , Littmann Maria , Lu Amy X. , Yang Kevin K. , Min Seonwoo , Yoon Sungroh , Morton James T. , Rost Burkhard 
Published: May 2021

AbstractModels from machine learning (ML) or artificial intelligence (AI) increasingly assist in guiding experimental design and decision making in molecular biology and medicine. Recently, Language Models (LMs) have been adapted from Natural Language Processing (NLP) to encode the implicit language written in protein sequences. Protein LMs show enormous potential in generating descriptive representations (embeddings) for proteins from just their sequences, in a fraction of the time with respect to previous approaches, yet with comparable or improved predictive ability. Researchers have trained a variety of protein LMs that are likely to illuminate different angles of the protein language. By leveraging the bio_embeddings pipeline and modules, simple and reproducible workflows can be laid out to generate protein embeddings and rich visualizations. Embeddings can then be leveraged as input features through machine learning libraries to develop methods predicting particular aspects of protein function and structure. Beyond the workflows included here, embeddings have been leveraged as proxies to traditional homology‐based inference and even to align similar protein sequences. A wealth of possibilities remain for researchers to harness through the tools provided in the following protocols. © 2021 The Authors. Current Protocols published by Wiley Periodicals LLC.The following protocols are included in this manuscript:Basic Protocol 1: Generic use of the bio_embeddings pipeline to plot protein sequences and annotationsBasic Protocol 2: Generate embeddings from protein sequences using the bio_embeddings pipelineBasic Protocol 3: Overlay sequence annotations onto a protein space visualizationBasic Protocol 4: Train a machine learning classifier on protein embeddingsAlternate Protocol 1: Generate 3D instead of 2D visualizationsAlternate Protocol 2: Visualize protein solubility instead of protein subcellular localizationSupport Protocol: Join embedding generation and sequence space visualization in a pipeline
Association of masseter muscles thickness and facial morphology with facial expressions in children
Authors: Guédat Christophe , Stergiopulos Ourania , Kiliaridis Stavros , Antonarakis Gregory S. 
Published: May 2021

AbstractObjectiveTo evaluate the potential influence of muscular capacity and facial morphology on facial expressions in children.Materials and methodsA cross‐sectional study was carried out on 40 healthy children (ages 9–13), without previous orthodontic treatment. Masseter muscle thickness and anthropometric facial proportions were measured using ultrasound and digital calipers respectively. A three‐dimensional infrared face‐tracking system was used to register facial expressions. The maximal amplitude of smile and lip pucker (representing maximal lateral and medial commissure movement) were used for analysis. Stepwise regression was used to investigate whether muscle thickness or anthropometric facial proportions were associated with the quantity of commissure movement.ResultsWhen performing maximal smile, children with thicker masseter muscles were found to have more limited displacement of the commissures (R = 0.39; p = 0.036). When performing lip pucker, children with thicker masseter muscles were found to have greater commissure movement (R = 0.40; p = 0.030). No significant associations were found between anthropometric facial proportions and facial expressions.ConclusionMasseter muscle thickness seems to be associated with facial expressions in children. Those with thicker muscles show more limited commissure movement when smiling, but greater movement with lip pucker. This indicates that masticatory muscles may serve as a surrogate for mimic muscle activity. Facial morphology of the subjects does not seem to be associated with facial expression.
Influence of childhood asthma on dental caries: A longitudinal study
Authors: Samec Tomi , Amaechi Bennett Tochukwu , Jan Janja 
Published: May 2021

AbstractObjectivesThe study investigated the influence of childhood asthma on dental caries development and caries risk factors among children with asthma in Slovenia.Material and methodsThe study population consisted of 2–17 years old children (n = 138), who had used anti‐asthmatic medicines for at least 1 year. Controls were their non‐asthmatic siblings (n = 140). International Caries Detection and Assessment System‐II was used to assess caries status. After 3 years, 106 baseline participants (53 asthmatic and 53 siblings) were reexamined. Questionnaires completed by parents and data from the patients' medical records provided information on demographics, child's medical history, medication usage, and oral health behaviors. Additional 308 asthmatic children were examined to assess caries risk factors among children with asthma.ResultsAsthmatic children had significantly higher mean d12fs and D12MFS (p ≤ 0.05), and fewer caries‐free individuals (p ≤ 0.01). In asthmatic children, 3 years mean increment in D12MFS was significantly higher (p ≤ 0.05). Furthermore, progression over 3 years from sound tooth surfaces to decayed cavitated and filled lesions in primary and permanent teeth were present in significantly higher (p ≤ 0.05) percentage, and likewise transition from decayed cavitated lesions to missing tooth surfaces because of caries in primary teeth, and from filled to filled non‐cavitated and cavitated lesions in permanent teeth. Lower caries experience in asthmatic children was associated with lower doses of inhaled glucocorticoid use, leucotriene antagonist use, and daily milk and cheese consumption.ConclusionsAsthmatic children who had used anti‐asthmatic medicines had higher caries experience and higher caries progression over 3 years in both primary and permanent dentitions. Besides anti‐asthmatic medicines, other factors were associated with higher caries experience in asthmatic children.
Distribution of lip‐seal strength and its relation to oral motor functions
Authors: Kugimiya Yoshihiro , Oki Takeshi , Ohta Midori , Ryu Masahiro , Kobayashi Kenichiro , Sakurai Kaoru , Ueda Takayuki 
Published: May 2021

AbstractObjectivesLip‐seal strength, which represents the muscle strength of the lips, appears to chiefly contribute to mastication and pronunciation. However, the functional characteristics of lip‐seal strength in adults are still undefined. The present study aimed to understand not only the distribution of lip‐seal strength in adult men and women but also the effect of age on this strength and identify oral motor functions correlated with lip‐seal strength.Materials and methodsThe subjects included 339 participants (men: 170, age 39.2 ± 18.2 years; women: 169, age 43.1 ± 19.7 years). Oral motor function was evaluated for lip‐seal strength, oral diadochokinesis (ODK), tongue pressure, occlusal force, and masticatory performance. Statistical analyses included the Shapiro–Wilk, Mann–Whitney U, and Jonckheere–Terpstra tests, in addition to the Spearman's correlation analysis and curvilinear regression analysis.ResultsLip‐seal strength did not have a normal distribution (p < 0.001). The mean ± standard deviation and median (first quartile, third quartile) of lip‐seal strength were 11.2 ± 3.4 and 10.9 (8.7, 13.2)N for the whole sample, 12.3 ± 3.4 and 11.9 (9.4, 14.4)N for men, and 10.2 ± 3.0 and 9.9 (8.0, 12.0)N for women. A significant difference was observed in lip‐seal strength between men and women (p < 0.001). Oral motor functions showed a marked correlation with lip‐seal strength, including tongue pressure, occlusal force, and masticatory performance and ODK (/pa/ and /ta/), tongue pressure, and masticatory ability in men and women, respectively. In women, lip‐seal strength declined with increase in age.ConclusionsLip‐seal strength was non‐normally distributed in both men and women, and lip‐seal strength was affected by age only in women. Lip‐seal strength and multiple oral motor functions were significantly correlated. Because the indicators of perioral muscle strength and performance were correlated with lip‐seal strength, lip‐seal strength may also partially reflect the condition of the perioral muscles.
The cold resistance of cottonseed during germination is related to the content of unsaturated fatty acids
Authors: Chen Ying , Tian Liwen , Wan Lu , Xia Jun , Liu Feng , Zhao Ruihai , Wang Tangang , Han Chunli 
Published: May 2021

AbstractThe agricultural industry is severely affected by low temperature due to its wide range of adverse effects. This work aimed to elucidate the changes in fatty acid composition during cotton (Gossypium L.) seed germination and the relationship of that change and germination characteristics. Three temperatures, 15/12 (T12), 21/18 (T18), and 25/25 °C day/night (T25), were set to treat Xinluzao 65 (L65) and Xinhai 35 (H35). Under T12, the germination rate, germination index, and water absorption rate of the cotton seeds decreased, and the mean time of germination increased compared to T25. The germination rate, germination index and water absorption rate of H35 were 6.67, 5.15, and 17% higher, respectively, than those of L65 under the T2 treatment. The total lipids, saturated fatty acid/unsaturated fatty acid (SFA/UFA) ratio, and monounsaturated fatty acid/polyunsaturated fatty acid (MUFA/PUFA) ratio were 3.75, 0.30, and 4.98% higher, respectively, in H35 than in L65 under the T25 treatment. The water absorption rate of L65 was significantly positively correlated with C18:2 and significantly negatively correlated with C24:0 and C18:1. The water absorption rate and germination rate of H35 were significantly positively correlated with C14:0 and C16:1, and C18:2 was significantly negatively correlated with the germination rate and the water absorption rate. Therefore, low‐temperature stress in cotton results in an increase in the water absorption rate and consequent decreases in the concentrations of SFAs C20:0, C22:0, and C24:0, as well as an increase in the concentration of UFA C16:1. These changes enhance the ability of cotton seeds to resist cold damage.
Formic Acid as a Potential On‐Board Hydrogen Storage Method: Development of Homogeneous Noble Metal Catalysts for Dehydrogenation Reactions
Authors: Guo Jian , Yin Chengkai K. , Zhong Dulin L. , Wang Yilin L. , Qi Tiangui , Liu Guihua H. , Shen Leiting T. , Zhou Qiusheng S. , Peng Zhihong H. , Yao Hong , Li Xiaobin B. 
Published: May 2021

AbstractHydrogen can be used as an energy carrier for renewable energy to overcome the deficiency of its intrinsically intermittent supply. One of the most promising application of hydrogen energy is on‐board hydrogen fuel cells. However, the lack of a safe, efficient, convenient, and low‐cost storage and transportation method for hydrogen limits their application. The feasibility of mainstream hydrogen storage techniques for application in vehicles is briefly discussed in this Review. Formic acid (FA), which can reversibly be converted into hydrogen and carbon dioxide through catalysis, has significant potential for practical application. Historic developments and recent examples of homogeneous noble metal catalysts for FA dehydrogenation are covered, and the catalysts are classified based on their ligand types. The Review primarily focuses on the structure−function relationship between the ligands and their reactivity and aims to provide suggestions for designing new and efficient catalysts for H2 generation from FA.
Regulating Utilization Efficiency of the Photogenerated Charge Carriers by Constructing Donor–π–Acceptor Polymers for Upgrading Photocatalytic CO2Reduction
Authors: Chen Jinqing , Zhong Hong , Lv Haowei , Liu Ruixia , Wang Ruihu 
Published: May 2021

AbstractPhotocatalytic CO2reduction offers a promising approach for managing global carbon balance. The smooth delivery of the photoexcited electrons to the active sites without the extra photosensitizers is still challenging. Herein, a series of donor–π–acceptor conjugated organic polymers (COPs) were produced using anthracene, cobalt‐coordinated bipyridyl, and benzene as donor, acceptor, and π linker units, respectively. The introduction of phenyl linker significantly improved the activities of photocatalytic CO2reduction upon visible light illumination. Structure–performance relationship examinations uncovered that donor–π–acceptor structure promotes mobility of charge carriers and utilization efficiency on the catalytically active sites, resulting in high photocatalytic activity and durability for CO2photoreduction. The in‐depth insights into the electron transport processes open new perspectives for further optimization and rational design of photoactive polymers with high efficiency for solar‐energy conversion.
DebarcodeR increases fluorescent cell barcoding capacity and accuracy
Authors: Reisman Benjamin J. , Barone Sierra M. , Bachmann Brian O. , Irish Jonathan M. 
Published: May 2021

AbstractFluorescent cell barcoding (FCB) enables efficient collection of tens to hundreds of flow cytometry samples by covalently marking cells with varying concentration of spectrally distinct dyes. A key consideration in FCB is to balance the density of dye barcodes, the complexity of cells in the sample, and the desired accuracy of the debarcoding. Unfortunately, barcoding bench and computational methods have not benefited from the high dimensional revolution in cytometry due to a lack of automated computational tools that effectively balance these common cytometry needs. DebarcodeR addresses these unmet needs by providing a framework for computational debarcoding augmented by improvements to experimental methods. Adaptive regression modeling accounted for differential dye uptake between different cell types and Gaussian mixture modeling provided a robust method to probabilistically assign cells to samples. Assignment tolerance parameters are available to allow users to balance high cell recovery with accurate assignments. Improvements to experimental methods include: (1) inclusion of an “external standard” control where a pool of all cells was stained a single level of each barcoding dyes and (2) an “internal standard” where each cell is stained with a single level of a separate dye. DebarcodeR significantly improved speed, accuracy, and reproducibility of FCB while avoiding selective loss of unusual cell subsets when debarcoding microtiter plates of cell lines and heterogenous mixtures of primary cells. DebarcodeR is available on Github as an R package that works with flowCore and Cytoverse packages at github.com/cytolab/DebarcodeR.
Which hand knows the “right” word? What hand selection reveals about vocabulary in pre‐and school‐aged children
Authors: van Rootselaar Nicole A. , Grandmont Dana , Gibb Robbin , Li Fangfang , Gonzalez Claudia L. R. 
Published: May 2021

AbstractResearch has shown that infants with increased right‐hand selection for their first gestures perform better at an array of language tasks when they are tested later as toddlers. There is a smaller body of literature which focuses on preschoolers and how their right‐handed movements relate to their speech and vocabulary development. Some research has established a connection between right‐hand preference for grasping and speech production ability in preschool children, but the link to gestures is relatively unexplored in this age group. We investigated if lateralized gestures (pointing) are related to measures of language development (vocabulary) in a preschool‐age sample. Specifically, typically developing children (aged 3–6) completed the Peabody Picture Vocabulary Test (PPVT) to assess receptive language. We recorded their hand preference for pointing during the PPVT and the incidence of mistakes (pointing to the wrong picture). Despite the length of the test, children were more likely to select a correct response with their right hand. This result suggests a relationship between lateralized communicative gestures (pointing) and receptive language. This study provides evidence for an intimate relationship between right‐handed manual movement and language development. Implications of this finding include developing simple fine‐motor tasks to detect and/or ameliorate delayed language development.