bluuebunny/crossref_metadata_2025_split huggingface dataset:
Artificial neural network‐based quantitative structure–activity relationships model and molecular docking for virtual screening of novel potent acetylcholinesterase inhibitors
Authors: Zerroug Enfale , Belaidi Salah , Chtita Samir 
Published: March 2021

AbstractThe deficit in cholinergic neurotransmission is the main incentives for the development of new therapeutic drugs for the treatment of Alzheimer's disease (AD). In this study, we employed cheminformatics tools to explore new molecules that can serve as effective therapeutic agents against AD. Artificial neural networks (ANNs) were applied in a quantitative structure anti‐acetylcholinesterase (AChE)‐activity relationship study on a series of AChE inhibitors (AChEIs). The best computational neural network had an [5‐10‐12‐1] architecture, with a low value of mean squared error (MSE = 0.06) and a high value of R2 (0.96). All validations showed that the ANN model can be used quite satisfactorily for the screening of a new series of molecules having anti‐AChE activity. The virtual screening based on the molecular similarity method and applicability domain of ANN‐quantitative structure–activity relationships allowed the discovery of novel anti‐AChE candidates with improved activity. Docking simulation carried out on these novel AChEIs has identified eight best hits with a higher binding affinity toward their target (4EY7). These eight stable complexes were in good agreement with the biological activity and they have an inhibition profile at a similar rate as the reference drug donepezil. The results showed that these compounds were strongly bound up with the AChE enzyme active site with the optimal conformations.
Methodological improvements to a Procedure for Rapidly Establishing Steady‐State Behavior
Authors: Klapes Bryan , Ginalis Christine L. , McDowell J. J 
Published: March 2021

We performed three experiments to improve the quality and retention of data obtained from a Procedure for Rapidly Establishing Steady‐State Behavior (PRESS‐B; Klapes et al., 2020). In Experiment 1, 120 participants worked on nine concurrent random‐interval random‐interval (conc RI RI) schedules and were assigned to four conditions of varying changeover delay (COD) length. The 0.5‐s COD condition group exhibited the fewest instances of exclusive reinforcer acquisition. Importantly, this group did not differ in generalized matching law (GML) fit quality from the other groups. In Experiment 2, 60 participants worked on nine conc RI RI schedules with a wider range of scheduled reinforcement rate ratios than was used in Experiment 1. Participants showed dramatic reductions in exclusive reinforcer acquisition. Experiment 3 entailed a replication of Experiment 2 wherein blackout periods were implemented between the schedule presentations and each schedule remained in operation until at least one reinforcer was acquired on each alternative. GML fit quality was slightly more consistent in Experiment 3 than in the previous experiments. Thus, these results suggest that future PRESS‐B studies should implement a shorter COD, a wider and richer scheduled reinforcement rate ratio range, and brief blackouts between schedule presentations for optimal data quality and retention.
Outcomes from a multimodal, at‐scale community‐based HIV counselling and testing programme in twelve high HIV burden districts in South Africa
Authors: Medina‐Marino Andrew , Daniels Joseph , Bezuidenhout Dana , Peters Remco , Farirai Thato , Slabbert Jean , Guloba Geoffrey , Johnson Suzanne , Bekker Linda‐Gail , Nkhwashu Nkhensani 
Published: March 2021

AbstractIntroductionFacility‐based HIV testing services (HTS) have been less acceptable and accessible by adolescents, men and key populations in South Africa. Community‐based HIV counselling and testing (CBCT) modalities, including mobile unit and home‐based testing, have been proposed to decrease barriers to HIV testing uptake. CBCT modalities and approaches may be differentially acceptable to men and women based on age. Implementation of multimodal CBCT services may improve HIV testing rates among adolescents and men, and support the roll‐out of prevention services.MethodsA cross‐sectional analysis was conducted using aggregate, routine programmatic data collected from 1 October 2015 through 31 March 2017 from a multimodal, at‐scale CBCT programme implemented in 12 high‐burden districts throughout South Africa. Data collection tools were aligned to reporting standards for the National Department of Health and donor requirements. HIV testing rates (i.e. number of tests performed per 100,000 population using South African census data) and testing proportions by modality were stratified by sex, age groups and heath districts. Descriptive statistics were performed using STATA 13.0.ResultsOverall, 944,487 tests were performed during the 1.5‐year testing period reported. More tests were conducted among females than males (53.6% vs. 46.4%). Overall, 8206 tests per 100,000 population (95% CI: 8190.2 to 8221.9) were performed; female‐to‐male (F:M) testing ratio was 1.11. Testing rates were highest among young women age 20 to 24 years (16,328.4; 95% CI: 16,237.9 to 16,419.1) and adolescent girls aged 15 to 19 years (12,817.0; 95% CI: 12,727.9 to 12,906.6). Home‐based testing accounted for 61.3% of HIV tests, followed by near‐home mobile unit testing (30.2%) and workplace mobile unit testing (4.7%). More women received HTS via home‐based testing (F:M ratio = 1.29), whereas more men accessed work‐place mobile testing (M:F ratio = 1.35). No sex differential was observed among those accessing near‐home mobile testing (F:M ratio = 0.98).ConclusionsConcurrent implementation of multiple, targeted CBCT modalities can reduce sex disparities in HIV testing in South Africa. Given the acceptability and accessibility of these CBCT services to adolescent girls and young women, evident from their high testing rates, leveraging community‐based services delivery platforms to increase access to HIV prevention services, including pre‐exposure prophylaxis (PrEP), should be considered.
Impact of gender on patients hospitalized for SARS‐COV‐2 infection: A prospective observational study
Authors: Giacomelli Andrea , De Falco Teresa , Oreni Letizia , Pedroli Alice , Ridolfo Anna Lisa , Calabrò Elisa , Carrozzo Giorgia , Bonazzetti Cecilia , Antinori Spinello , Brucato Antonio 
Published: March 2021

AbstractBiological sex could affect the natural history of severe acute respiratory syndrome coronavirus 2 infection. We enrolled all COVID‐19 patients admitted to two COVID‐19 hospitals in Milan in a prospective observational study. The primary outcome was death during the study period and the secondary outcome was critical disease at hospital admission. The association(s) between clinically relevant, noncollinear variables, and the primary outcome was assessed with uni‐ and multivariable Logistic regression models. A total of 520 patients were hospitalized of whom 349 (67%) were males with a median age 61 (interquartile range: 50–72). A higher proportion of males presented critically ill when compared to females (30.1% vs. 18.7%, p < .046). Death occurred in 86 (24.6%) males and 27 (15.8%) females (p = .024). In multivariable analysis age (per 10 years more) (adjusted odds ratio [AOR]: 1.83 [95% confidence interval {CI}: 1.42–2.35], p < .0001), obesity (AOR: 2.17 [95% CI: 1.10–4.31], p = .026), critical disease at hospital admission (AOR 6.34 [95% CI: 3.50–11.48], p < .0001) were independently associated to higher odds of death whereas gender was not. In conclusion, a higher proportion of males presented critically ill at hospital admission. Age, critical disease at hospital admission, obesity, anemia, D‐dimer, estimated glomerular filtration rate, lactate dehydrogenase, and creatine kinase predicted death in hospitalized COVID‐19 patients.
Both living and dead Faecalibacterium prausnitzii alleviate house dust mite‐induced allergic asthma through the modulation of gut microbiota and short‐chain fatty acid production
Authors: Hu Wenbing , Lu Wenwei , Li Lingzhi , Zhang Hao , Lee Yuan‐kun , Chen Wei , Zhao Jianxin 
Published: March 2021

AbstractBACKGROUNDAsthma is increasingly prevalent worldwide, and novel strategies to prevent or treat this disease are needed. Probiotic intervention has recently been reported to be effective for asthma prevention. Here, we explored the effects of Faecalibacterium prausnitzii on the development of allergic airway inflammation in a murine model of house dust mite (HDM)‐induced allergic asthma.RESULTSSupplementation with living and dead F. prausnitzii blocked eosinophil, neutrophil, lymphocyte and macrophage influx and alleviated the pathological changes. Moreover, both living and dead F. prausnitzii administration decreased the levels of interleukin (IL)‐4, IL‐5, IL‐13 and immunoglobulin G1, elevated regulatory T cell (Tregs) ratio, improved microbial dysbiosis and enhanced short‐chain fatty acid (SCFA) production. Network correlation analysis revealed that the immune indicators were strongly associated with SCFA production. Based on the linear discriminant analysis effect size, Turicibacter was found to be the core genus related to HDM‐induced asthma. Living F. prausnitzii treatment enriched Faecalibaculum, Dubosiella and Streptococcus, while dead F. prausnitzii treatment increased Muribaculaceae and Parabacteroides. Interestingly, both living and dead F. prausnitzii administration enriched Lachnoclostridium and normalized the pathways involving carbohydrate and lipid metabolism, which might be related to SCFA production.CONCLUSIONFaecalibacterium prausnitzii exerts an anti‐asthmatic effect partly by gut microbiota modulation and SCFA production, suggesting its potential as a probiotic agent for allergic asthma prevention. © 2021 Society of Chemical Industry
Near‐infrared stimulation of the auditory nerve: A decade of progress toward an optical cochlear implant
Authors: Littlefield Philip D. , Richter Claus‐Peter 
Published: March 2021

AbstractObjectivesWe provide an appraisal of recent research on stimulation of the auditory system with light. In particular, we discuss direct infrared stimulation and ongoing controversies regarding the feasibility of this modality. We also discuss advancements and barriers to the development of an optical cochlear implant.MethodsThis is a review article that covers relevant animal studies.ResultsThe auditory system has been stimulated with infrared light, and in a much more spatially selective manner than with electrical stimulation. However, there are experiments from other labs that have not been able to reproduce these results. This has resulted in an ongoing controversy regarding the feasibility of infrared stimulation, and the reasons for these experimental differences still require explanation. The neural response characteristics also appear to be much different than with electrical stimulation. The electrical stimulation paradigms used for modern cochlear implants do not apply well to optical stimulation and new coding strategies are under development. Stimulation with infrared light brings the risk of heat accumulation in the tissue at high pulse repetition rates, so optimal pulse shapes and combined optical/electrical stimulation are being investigated to mitigate this. Optogenetics is another promising technique, which makes neurons more sensitive to light stimulation by inserting light sensitive ion channels via viral vectors. Challenges of optogenetics include the expression of light sensitive channels in sufficient density in the target neurons, and the risk of damaging neurons by the expression of a foreign protein.ConclusionOptical stimulation of the nervous system is a promising new field, and there has been progress toward the development of a cochlear implant that takes advantage of the benefits of optical stimulation. There are barriers, and controversies, but so far none that seem intractable.Level of evidenceNA (animal studies and basic research).
Genome‐wide profiling of miRNAs during seed development reveals their functional relevance in seed size/weight determination in chickpea
Authors: Khemka Niraj , Singh Rajkumar Mohan , Garg Rohini , Jain Mukesh 
Published: March 2021

AbstractMicroRNAs (miRNAs) are non‐coding small RNAs that regulate gene expression at transcriptional and post‐transcriptional levels. The role of miRNAs in seed development and seed size/weight determination is poorly understood in legumes. In this study, we profiled miRNAs at seven successive stages of seed development in a small‐seeded and a large‐seeded chickpea cultivar via small RNA sequencing. In total, 113 known and 243 novel miRNAs were identified. Gene ontology analysis revealed the enrichment of seed/reproductive/post‐embryonic development and signaling pathways processes among the miRNA target genes. A large fraction of the target genes exhibited antagonistic correlation with miRNA expression. The sets of co‐expressed miRNAs showing differential expression between the two cultivars were recognized. Known transcription factor (TF) encoding genes involved in seed size/weight determination, including SPL, GRF, MYB, ARF, HAIKU1, SHB1, KLUH/CYP78A5, and E2Fb along with novel genes were found to be targeted by the predicted miRNAs. Differential expression analysis revealed higher transcript levels of members of SPL and REVOLUTA TF families and lower expression of their corresponding miRNAs in the large‐seeded cultivar. At least 19 miRNAs known to be involved in seed development or differentially expressed between small‐seeded and large‐seeded cultivars at late‐embryogenesis and/or mid‐maturation stages were located within known quantitative trait loci (QTLs) associated with seed size/weight determination. Moreover, 41 target genes of these miRNAs were also located within these QTLs. Altogether, we revealed important roles of miRNAs in seed development and identified candidate miRNAs and their target genes that have functional relevance in determining seed size/weight in chickpea.
Interjecting the geographies of skills into international skilled migration research: Political economy and ethics for a renewed research agenda
Authors: Raghuram Parvati 
Published: March 2021

AbstractThere is now a large literature on skilled migration, which uses multiple definitions, concepts, theories and understandings of skilled migrants. However, this research has not adequately considered the geographies of skills—the spatial and temporal relations through which skills get meaning, are accrued and claimed and their outcomes and how these shape and are shaped by skilled mobilities and migration. This paper explores sites and networks as two interrelated elements of a geography of skills in order to highlight how they have prescribed, produced, prevailed and precluded who attains the skills to migrate. The paper goes on to outline how and why the geographies of skills and skilled migration matter in contemporary knowledge capitalism and the ethical issues they raise for a renewed research agenda on skilled migration. Crucially, it suggests that the spatio‐temporal configurations of skills raise not only empirical and analytical questions but also normative ones about the politics and ethics of skilling.
The catalytic effects of H2O, basic and acidic catalysts on the gas‐phase hydrolysis mechanism of carbonyl fluoride (CF2O)
Authors: Lu Yousong , Zhang Tianlei , Lily Makroni , Wang Weina , Liu Fengyi , Wang Wenliang 
Published: March 2021

AbstractThe carbonyl fluoride (CF2O) is one of the significant atmospheric molecules, and its hydrolysis reaction has been considered the most potential removal process in the earth's troposphere. In this article, the hydrolysis reaction of CF2O assisted by H2O, basic (NH3 and CH3NHCH3), and acidic (H2SO4, HCOOH, and CF3COOH) catalysts have theoretically investigated using quantum chemical methods. These catalysts significantly decrease the hydrolysis reaction of barrier height by 20.4–28.8 kcal mol−1. Here two H‐transfer mechanisms have been identified in these catalyzed hydrolytic reactions as asynchronous collaborative caused by base molecules and the synchronous collaborative led by H2O and acid molecules. In addition, the rate coefficient and relative rate of all catalytic reactions have calculated using conventional transition state theory (TST) over a temperature range of 280–320 K. The results show that H2SO4 has the best catalytic effect without considering the concentration of catalyst molecules in the atmosphere. On the contrary, a high concentration of HCOOH (10 ppbv) is dominant in the catalytic reaction when considered the concentrations of catalyst molecules. In this work, it was identified that the catalytic efficiencies of H2O, acid and base molecules upon addition reaction between CF2O and H2O is not only related to their catalytic mechanisms but also depending upon their concentrations in the atmosphere.
Printed Stretchable Liquid Metal Electrode Arrays for In Vivo Neural Recording
Authors: Dong Ruihua , Wang Lulu , Hang Chen , Chen Zhen , Liu Xiaoyan , Zhong Leni , Qi Jie , Huang Yuqing , Liu Shaoqin , Wang Liping , Lu Yi , Jiang Xingyu 
Published: March 2021

AbstractThe adoption of neural interfacing into neurological diagnosis is severely hampered by the complex, costly, and error‐prone manufacturing methods, requiring new fabrication processes and materials for flexible neural interfacing. Here a strategy for fabricating highly stretchable neural electrode arrays based on screen printing of liquid metal conductors onto polydimethylsiloxane substrates is presented. The screen‐printed electrode arrays show a resolution of 50 µm, which is ideally applicable to neural interfaces. The integration of liquid metal–polymer conductor enables the neural electrode arrays to retain stable electrical properties and compliant mechanical performance under a significant (≈108%) strain. Taking advantage of its high biocompatibility, liquid metal electrode arrays exhibit excellent performance for neurite growth and long‐term implantation. The stretchable electrode arrays can spontaneously conformally come in touch with the brain surface, and high‐throughput electrocorticogram signals are recorded. Based on stretchable electrode arrays, real‐time monitoring of epileptiform activities can be provided at different states of seizure. The method reported here offers a new fabrication strategy to manufacture stretchable neural electrodes, with additional potential utility in diagnostic brain–machine interfaces.
Hybridized Radial and Edge Coupled 3D Plasmon Modes in Self‐Assembled Graphene Nanocylinders
Authors: Dai Chunhui , Agarwal Kriti , Bechtel Hans A. , Liu Chao , Joung Daeha , Nemilentsau Andrei , Su Qun , Low Tony , Koester Steven J. , Cho Jeong‐Hyun 
Published: March 2021

AbstractCurrent graphene‐based plasmonic devices are restricted to 2D patterns defined on planar substrates; thus, they suffer from spatially limited 2D plasmon fields. Here, 3D graphene forming freestanding nanocylinders realized by a plasma‐triggered self‐assembly process are introduced. The graphene‐based nanocylinders induce hybridized edge (in‐plane) and radial (out‐of‐plane) coupled 3D plasmon modes stemming from their curvature, resulting in a four orders of magnitude stronger field at the openings of the cylinders than in rectangular 2D graphene ribbons. For the characterization of the 3D plasmon modes, synchrotron nanospectroscopy measurements are performed, which provides the evidence of preservation of the hybridized 3D graphene plasmons in the high precision curved nanocylinders. The distinct 3D modes introduced in this paper, provide an insight into geometry‐dependent 3D coupled plasmon modes and their ability to achieve non‐surface‐limited (volumetric) field enhancements.
On bounds for steady waves with negative vorticity
Authors: Lokharu Evgeniy 
Published: March 2021

AbstractWe prove that no two-dimensional Stokes and solitary waves exist when the vorticity function is negative and the Bernoulli constant is greater than a certain critical value given explicitly. In particular, we obtain an upper bound$$F \le \sqrt{2} + \epsilon $$F≤2+ϵfor the Froude number of solitary waves with a negative constant vorticity, sufficiently large in absolute value.
Data-driven assessment, contextualisation and implementation of 134 variables in the risk for type 2 diabetes: an analysis of Lifelines, a prospective cohort study in the Netherlands
Authors: van der Meer Thomas P. , Wolffenbuttel Bruce H. R. , Patel Chirag J. 
Published: March 2021

AbstractAims/hypothesisWe aimed to assess and contextualise 134 potential risk variables for the development of type 2 diabetes and to determine their applicability in risk prediction.MethodsA total of 96,534 people without baseline diabetes (372,007 person-years) from the Dutch Lifelines cohort were included. We used a risk variable-wide association study (RV-WAS) design to independently screen and replicate risk variables for 5-year incidence of type 2 diabetes. For identified variables, we contextualised HRs, calculated correlations and assessed their robustness and unique contribution in different clinical contexts using bootstrapped and cross-validated lasso regression models. We evaluated the change in risk, or ‘HR trajectory’, when sequentially assigning variables to a model.ResultsWe identified 63 risk variables, with novel associations for quality-of-life indicators and non-cardiovascular medications (i.e., proton-pump inhibitors, anti-asthmatics). For continuous variables, the increase of 1 SD of HbA1c, i.e., 3.39 mmol/mol (0.31%), was equivalent in risk to an increase of 0.53 mmol/l of glucose, 19.8 cm of waist circumference, 8.34 kg/m2of BMI, 0.67 mmol/l of HDL-cholesterol, and 0.14 mmol/l of uric acid. Other variables required an increase of >3 SD, which is not physiologically realistic or a rare occurrence in the population. Though moderately correlated, the inclusion of four variables satiated prediction models. Invasive variables, except for glucose and HbA1c, contributed little compared with non-invasive variables. Glucose, HbA1cand family history of diabetes explained a unique part of disease risk. Adding risk variables to a satiated model can impact the HRs of variables already in the model.ConclusionsMany variables show weak or inconsistent associations with the development of type 2 diabetes, and only a handful can reliably explain disease risk. Newly discovered risk variables will yield little over established factors, and existing prediction models can be simplified. A systematic, data-driven approach to identify risk variables for the prediction of type 2 diabetes is necessary for the practice of precision medicine.Graphical abstract