bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adverse maternal environment alters Oprl1 variant expression in mouse hippocampus
Authors: Ke Xingrao , Huang Yingliu , Fu Qi , Majnik Amber , Sampath Venkatesh , Lane Robert H. 
Published: August 2022

AbstractAn adverse maternal environment (AME) and Western diet (WD) in early life predispose offspring toward cognitive impairment in humans and mice. Cognitive impairment associates with hippocampal dysfunction. An important regulator of hippocampal function is the hippocampal Nociceptin/Orphanin FQ (N/OFQ) system. Previous studies find links between dysregulation of hippocampal N/OFQ receptor (NOP) expression and impaired cognitive function. NOP is encoded by the opioid receptor‐like 1 (Oprl1) gene that contains multiple mRNA variants and isoforms. Regulation of Oprl1 expression includes histone modifications within the promoter. We tested the hypothesis that an AME and a postweaning WD increase the expression of hippocampal Oprl1 and select variants concurrent with altered histone code in the promoter. We created an AME‐WD model combining maternal WD and prenatal environmental stress plus postweaning WD in the mouse. We analyzed the hippocampal expression of Oprl1, Oprl1 variants, and histone modifications in the Oprl1 promoter in offspring at postnatal day (P) 21 and P100. An AME and an AME‐WD significantly increased the total hippocampal expression of Oprl1 and variant V4 concurrently with an increased accumulation of active histone marks in the promoter of male offspring. We concluded that an AME and an AME‐WD alter hippocampal Oprl1 expression in offspring through an epigenetic mechanism in a variant‐specific and sex‐specific manner. Altered hippocampal Oprl1 expression may contribute to cognitive impairment seen in adult males in this model. Epigenetic regulation of Oprl1 is a potential mechanism by which an AME and a WD may contribute to neurocognitive impairment in male offspring.
Effect of ABCB1 gene variants on rivaroxaban pharmacokinetic and hemorrhage events occurring in patients with non‐valvular atrial fibrillation
Authors: Zhang Dan , Qin Wei , Du Wenwen , Wang Xiaoxing , Chen Wenqian , Li Pengmei 
Published: August 2022

AbstractHemorrhage events occur most frequently in anticoagulant therapy for non‐valvular atrial fibrillation (NVAF). Rivaroxaban is used widely for routine anticoagulation care. Genetic polymorphisms are thought to contribute to the wide intraindividual variability seen in rivaroxaban metabolism and the anticoagulant response. The aim of this study was to evaluate the effect of drug transport related single‐nucleotide polymorphisms (SNPs) on rivaroxaban metabolism and on the risk of a hemorrhage event. A total of 216 Chinese patients with NVAF were enrolled in the study. Rivaroxaban was used for anticoagulation therapy. Rivaroxaban plasma concentrations were detected using a validated ultra‐performance liquid chromatography‐tandem mass spectrometry (UPLC‐MS/MS) method. Seven SNPs in four genes were genotyped using the Sanger dideoxy DNA sequencing method. Associations between genotype variants, the incidence of hemorrhage events, and the time of bleeding were analyzed. ABCB1 2677G (rs2032582) variation was highly associated with the dose‐adjusted rivaroxaban peak concentration in plasma (Cmax/D) (p = 0.025, FDR = 0.042). The ABCB1 G allele carriers had a higher rivaroxaban Cmax/D than non‐carriers. Logistic regression showed that rivaroxaban Cmax/D and ABCB1 genotype variants were associated with a higher incidence of hemorrhage events. No statistically significant difference was found between ABCB1 genotypes and the time of bleeding after anticoagulant therapy in 30 days. These results indicated that ABCB1 2677G (rs2032582) genetic variant affects the rivaroxaban Cmax/Dose and the incidence of hemorrhage events significantly.
On the relevance of prognostic information for clinical trials: A theoretical quantification
Authors: Siegfried Sandra , Senn Stephen , Hothorn Torsten 
Published: August 2022

AbstractThe question of how individual patient data from cohort studies or historical clinical trials can be leveraged for designing more powerful, or smaller yet equally powerful, clinical trials becomes increasingly important in the era of digitalization. Today, the traditional statistical analyses approaches may seem questionable to practitioners in light of ubiquitous historical prognostic information. Several methodological developments aim at incorporating historical information in the design and analysis of future clinical trials, most importantly Bayesian information borrowing, propensity score methods, stratification, and covariate adjustment. Adjusting the analysis with respect to a prognostic score, which was obtained from some model applied to historical data, received renewed interest from a machine learning perspective, and we study the potential of this approach for randomized clinical trials. In an idealized situation of a normal outcome in a two‐arm trial with 1:1 allocation, we derive a simple sample size reduction formula as a function of two criteria characterizing the prognostic score: (1) the coefficient of determination R2 on historical data and (2) the correlation ρ between the estimated and the true unknown prognostic scores. While maintaining the same power, the original total sample size n planned for the unadjusted analysis reduces to in an adjusted analysis. Robustness in less ideal situations was assessed empirically. We conclude that there is potential for substantially more powerful or smaller trials, but only when prognostic scores can be accurately estimated.
Can low‐carbon development force enterprises to make digital transformation?
Authors: Chen Wen 
Published: August 2022

AbstractEnterprises need to innovate business strategies to deal with the negative effects of low‐carbon development, among which digital transformation is an important breakthrough technology. This paper discusses the impact of low‐carbon development on enterprises' digital transformation. Theoretical analysis shows that environmental regulations driven by low‐carbon development have the compensatory effect of stimulating enterprise digital transformation to mitigate misallocation of capital and labor, especially for enterprises with higher productivity. In addition, both the construction of network infrastructure and the development of digital finance can strengthen the incentives for enterprises' digital transformation. The empirical tests based on Chinese A‐share listed enterprises show that the degree of enterprises' digital transformation increases by 0.0122 standard deviation for every one standard deviation reduction in regional carbon emission intensity. These results deepen the understanding of the relationship between green development and microenterprise digitalization.
Serious games in future skills development: A systematic review of the design approaches
Authors: Gurbuz Suleyman C. , Celik Metin 
Published: August 2022

AbstractSerious games offer a magnificent potential for developing future skills along with the 21st‐century learning ecosystem. A close nexus between the design and effectiveness of serious games is still argued. In this regard, the current study provides a systematic literature review on serious game design approaches with a special focus on future skill development. A systematic review protocol, including planning, conducting, and reporting stages, is followed to comprehensively interpret the existing studies. Applying quality controls, 32 serious game studies which include a practical serious game design approach are selected. For providing a more systematic analysis, these approaches are then categorized based on the intended outcome of the serious game that the approach aims to facilitate. It is found that 8 (25%) of these design approaches support at least one future skills, among which problem‐solving as well as collaboration and teamwork are the most commonly supported ones. It is also discovered that clear goals and interactivity, used in 6 (75%) and 5 (63%) of the 8 design approaches respectively, are the most commonly implemented game design elements. Considering the significant literature gap on the implementation of serious games for future skills development, this study consequently provides valuable insights for the game designers, software developers, educational technology researchers, and engineering educators in various domains.
The design and implementation of a 16 bit floating point arithmetic unit using BZK.SAU.FPGA microcomputer assembly language
Authors: Öztekin Halit , Kişioğlu Hakan , Gülbağ Ali , Temurtaş Feyzullah 
Published: August 2022

AbstractThe microcomputer architecture named BZK.SAU.FPGA, which was developed in 2014, was used to increase efficiency in the teaching of the Computer Architecture and Organization course, which is one of the basic courses of the Department of Computer Engineering. In the last version released in 2018, the architecture has been started to be used in many engineering disciplines with its modular structure and a basic operating system. However, this architecture uses fixed‐point numbers in arithmetic operations. Although this situation contributes to its use as an educational tool at the beginner level for new learners, the fact that it cannot operate with floating point numbers is one of the biggest shortcomings of the educational tool. Floating point numbers are used extensively in applications such as mathematical analysis, signal processing, image processing, and so on. Therefore, in this study, the FPA unit for the computation of addition, subtraction, multiplication, and division operations is integrated into this architecture. For FPA unit implementation, an assembly‐level program has been embedded in the architecture using an IEEE‐754 half‐precision binary format (FP16) with the aim of presenting the fundamental of the floating‐point computation. The FPA unit proposed to observe the behavior of floating point numbers in arithmetic operations and increase awareness of these issues was used as an auxiliary tool in the computer architecture course. A pre‐ and postsurvey study was conducted to see the learning outcomes of students using this tool on floating point numbers. We found a significant association between pre‐ and postsurvey, indicating that students' knowledge about the behavior of floating point numbers increased (p < .001).
Two Novel Flavonoids with Lipid‐Lowering Activity from Yi Medicine Shekaqi
Authors: Lin Yu‐Ping , Fu Sheng‐Nan , Li Xin‐Ping , Wang Meng‐Meng , Fang Qiong‐Lian , Qiao Xue , Yan Qi , Hua Yan 
Published: August 2022

AbstractYi medicine Shekaqi is the most attractive traditional ethnic medicine due to its significant and diverse pharmacological activities. Two novel flavonoids, including 5,2′‐dihydroxy‐6‐methoxy‐7‐decyloxyflavone and tenaxin II‐7‐O‐β‐D‐glucuronopyranosyl acid butyl ester, along with six known flavonoids, were isolated from Yi medicine Shekaqi. Their structures were elucidated based on the analysis of their comprehensive spectral data. The in vitro lipid‐lowering activities of the eight compounds showed that all the compounds significantly inhibited the lipopolysaccharide (LPS)‐induced increase in the total cholesterol (TC) level, while compounds 1, 4, 6, 7, and 8 significantly inhibited the LPS‐induced increase in the triglyceride (TG) level.
Design, Synthesis and Cytotoxicity Evaluation of Novel Indole Derivatives of Panaxadiol
Authors: Han Linlin , Li Tao , Miao Dongyu , Lee Jungjoon , Xiao Shengnan , Piao Huri , Zhao Yuqing 
Published: August 2022

AbstractBased on the well‐known cytotoxicity of indole compounds, we used the ‘Fisher indole synthesis’ method to introduce appropriately substituted indole rings into panaxadiol (PD), generating eighteen novel Panaxadiol indole derivatives. Six human cancer cell lines (A549, HepG‐2, HCT‐116, SGC‐7901, MDA‐MB‐231, PC‐3 cells) and one normal ovarian cell lines (IOSE144) were designed to evaluate the anti‐proliferative activity of the PD derivatives. The results showed that the majority of PD derivatives showed enhanced anti‐proliferative activity, when compared with PD, with P‐Methylindolo‐PD exhibiting the highest cytotoxicity. In A549 cells, IC50 value was 5.01±0.87 μM, which is roughly 12 times higher than the activity of PD and 5 times that of 5‐FU. Moreover, cell morphology analysis and Annexin V‐FITC/PI assays exhibited that P‐Methylindolo‐PD could induce A549 cell apoptosis (55.7 % of apoptotic cells at 20 μM). Moreover, molecular docking experiments were performed to explore the molecular mechanism underlining the binding of P‐Methylindolo‐PD to the active site of EGFR. The results support that P‐Methylindolo‐PD might be a promising lead compound for further studies.
Sustainable Polyurethane‐Derived Heteroatom‐Doped Electrode Materials for Advanced Supercapacitors
Authors: Tang Jianguo , Zhao Yi , Sunarso Jaka , Wong Ngie Hing , Zhou Jin , Zhuo Shuping 
Published: August 2022

AbstractThis work presented a new method to recycle rigid polyurethane foam (RPUF) waste. A two‐step method to carbonize and activate RPUF was applied to synthesize sustainable polyurethane‐derived N, O co‐doped electrode materials for supercapacitors (SCs). Structural characterization showed a three‐dimensional honeycomb‐like pore structure rich with micro/mesopores formed with a 3647 m2 g−1 maximum specific surface area (SSA), and 2.04 at.% N and 8.30 at.% O were successfully co‐doped into the polyurethane porous carbons (PPCs). These properties created synergistic effects that enhanced the ion storage capacity and pseudocapacitance of the synthesized PPCs. As a result, the optimal PPC‐500‐800‐3 yielded excellent maximum specific capacitance in a three‐electrode (487 F g−1) and symmetric SC (324 F g−1) systems in a 1 m H2SO4 electrolyte at 1 A g−1 current density. Moreover, for the LiTFSI/H2O/(ACN)3.5 electrolyte, PPC‐500‐800‐3 produced a maximum energy density of 29.36 W kg−1 in a symmetric SC. After 10,000 cycles, PPC‐500‐800‐3 could achieve high cycling stability, maintaining 96.8 % of the initial capacitance at a 5 A g−1 current density.
Development of TfOH‐Catalyzed Spirocyclization by Intramolecular Friedel‐Crafts‐type 1,4‐Addition: Application to the Total Synthesis of the Unusual Proaporphine Alkaloid (±)‐Misrametine
Authors: Yoshida Keisuke , Hidaka Arisa , Fukami Yuri , Fujino Yuta , Imaizumi Yuri , Takao Ken‐ichi , Kitagaki Shinji 
Published: August 2022

AbstractAn effective method was developed for TfOH‐catalyzed construction of spiroindanes and spirotetralines containing an all‐carbon quaternary stereocenter. Intramolecular Friedel‐Crafts‐type 1,4‐addition of the substrates which were di‐ or trimethoxybenzene and 2‐cyclohexenone linked by an alkyl chain proceeded smoothly in the presence of 30 mol % of TfOH. A variety of spiroindanes and spirotetralines were obtained with moderate to excellent yield by this method. The reaction was successfully applied in the first total synthesis of the unusual proaporphine alkaloid (±)‐misrametine, which included the gram‐scale spirocyclization and selective O‐demethylation used KCN in DMSO condition as key steps.
CeO2C2 Nanoparticles with Oxygen‐Enriched Vacancies In‐site Self‐embedded in Fe, N Co‐doped Carbon Nanofibers as Efficient Oxygen Reduction Catalyst for Zn‐Air Battery†
Authors: Zhang Mingxin , Peng Hui , Sun Kanjun , Xie Xuan , Lei Xiaofei , Liu Sitong , Ma Guofu , Lei Ziqiang 
Published: August 2022

Comprehensive SummaryRational design of robust non‐noble electrocatalysts with numerous oxygen vacancies and highly reactive activity for oxygen reduction reaction (ORR) towards Zn‐air batteries is extremely paramount yet challenging. Herein, a novel CeO2C2 nanoparticles self‐embedded in Fe, N co‐doped carbon nanofibers (CeO2C2@Fe‐N‐C) heterostructure catalyst has been prepared by the in‐site dual template assisted electrospinning technique and subsequent high temperature pyrolysis strategy. Thanks to the CeO2C2 with oxygen‐enriched vacancies and versatile Fe‐N‐C with rich reactive species and high conductivity, CeO2C2@Fe‐N‐C catalyst exhibits outstanding catalytic performance in the ORR process, and shows excellent methanol tolerance and cycle stability. In addition, CeO2C2@Fe‐N‐C delivers a nearly four‐electron transfer process in the process of oxygen reduction catalysis, providing a fast‐electrochemical kinetic rate, which makes it an efficient air cathode for the Zn‐air battery. Importantly, the Zn‐air battery fabricated with CeO2C2@Fe‐N‐C cathode achieves superior performance including large open‐circuit voltage (1.5 V) and high specific capacity (780 mAh·g–1 at 10 mA·cm–2) together with superior reversibility and cycling stability, outperforming commercial Pt/C catalyst. The present work introduces a new strategy to design and develop highly active non‐noble catalysts and highlights the synergy from heterostructure in oxygen electrocatalysis for advanced Zn‐air batteries.
Visible‐Light Photocatalytic and Photo‐bactericidal Activity of Ni‐CuWO4/OTiO2 Composite†
Authors: Meng Shuangyan , Li Li , Xi Hui , Yang Jing , Xiao Ting , Zuo Rui , Xu Xueqing , Lei Ziqiang , Yang Zhiwang , Xue Qunji 
Published: August 2022

Comprehensive SummaryA series of nickel‐doped copper tungstate/oxygen‐rich TiO2 heterojunction‐constructed composites of xNi‐CuWO4/OTiO2 were successfully prepared to demonstrate the enhancement of the visible‐light photoactivity through promoting the photogenerated charge carrier separation efficiency. Of all these composites, 0.2Ni‐CuWO4/OTiO2 exhibits excellent and stable visible light photoactivity for the photooxidative coupling of benzylamine to the corresponding N‐benzyl‐1‐phenymethanimine (BPMI) in air atmosphere. The conversion of benzylamine and the selectivity to BPMI reach 97% and 99%, respectively. The catalyst shows good cyclability with the conversion of benzylamine decreasing just by 22% after being repeated six times with the well‐maintained selectivity of BPMI. The composite also exhibits excellent photo‐bactericidal ability, which greatly inhibits the reproducing of both the Gram‐positive bacteria (e.g., S. epidermidis) and Gram‐negative bacteria (e.g., E. coli).
Three‐stage auction scheme for computation offloading on mobile blockchain with edge computing
Authors: Xia Chengpeng , Wu Yalan , Chen Long , Chen Yawen , Wu Jigang 
Published: August 2022

SummaryBlockchain has been applied in wide range of fields to guarantee security. However, it has been very challenging for blockchain to flourish in mobile environment with limited resources. Existing studies mainly assume that single mobile user can buy the whole resources from edge servers in mobile blockchain. This paper formulates the problem of maximizing the social welfare for computation offloading in mobile blockchain. A three‐stage auction scheme with approximation ratio of based on group‐buying mechanism is proposed to allocate edge server resources for mobile blockchain applications. In the first stage, the miners are divided into groups, and a Vickrey–Clarke–Groves based auction is proposed to determine the bid of each group for each edge server. In the second stage, a matching algorithm is proposed to match edge servers and Access Points for maximizing the profit of edge servers. In the third stage, the edge server resources are allocated to mobile users for mining base on the results in the above stages. We prove that our auction scheme guarantees truthfulness, individual rationality and budget balance. Simulation results show that, the social welfare of our scheme is improved by 33.78%, 21.84%, 19.69%, and 6.69% for 1000 miners, compared with the existing works.
Diagnostic value of routine dental radiographs for predicting the mandibular canal localization validated by cone‐beam computed tomogram measurements
Authors: Wiechens Bernhard , Brockmeyer Phillipp , Sevinc Tayhan , Hoene Georg , Schliephake Henning , Hahn Wolfram 
Published: August 2022

AbstractObjectivesTo test the hypothesis that routine dental radiographs can be used to draw conclusions regarding the mandibular canal (MC) localization.Material and MethodsA total of 108 radiographs (36 orthopantomograms [OPTs], 36 lateral cephalograms [LCs], and 36 cone‐beam computed tomograms [CBCTs]) of 36 patients were analyzed. Statistical analysis included all cephalometric parameters obtained by OPTs, LCs, and CBCTs. Potential influencing parameters were calculated using linear and logistic regression with a backward removal algorithm. For predictability of MC localization, parameters were correlated using Pearson's correlation.ResultsThe MC ran along the lingual half (n = 24) twice as often as in the buccal half (n = 12) in the population studied. The position was always symmetrical contralaterally. No sex‐specific influence was observed (p = .34). Lingual and buccal MC courses were statistically significantly correlated to increased and decreased jaw angles (LC/OPT), respectively (p = .003; r = −.48/p = .010; r = −.42). An increased jaw angle was significantly correlated with a more cranial MC position (p = .013; r = −.41); a deep and distal bite position was significantly correlated with a caudal and buccal MC position (p = .004; r = −.47/p = .001; r = .57). Moreover, an increase of 1 point in the Hasund score predicted an increased probability of a buccal MC position by 18.6%. The jaw angle analyzed in OPT and LC images were positively correlated (r = .89, p < .001).ConclusionsRoutine dental radiographs provide informative guidance on the location of the MC in the vertical and transverse levels. This finding could be used in the initial consultation and treatment planning to consider more invasive diagnostic methods further down the line.
Fine mapping of QTL for water use efficiency‐related traits on chromosome 9 of Solanum habrochaites in the field
Authors: Groh Amy M. , Kubond Bryce A. , St. Clair Dina A. 
Published: August 2022

AbstractFresh water is increasingly limited due to climate change. One way to reduce fresh water use by irrigated agriculture is to breed plants that can produce adequate yields with less water. A wild tomato, Solanum habrochaites, is more water stress tolerant than cultivated tomato, S. lycopersicum L. Our study aimed to fine map quantitative trait loci (QTL) for maturity, yield, and water use efficiency (WUE)‐related traits (shoot dry weight and carbon isotope discrimination, ∆13C) on chromosome 9 in S. habrochaites using a set of 21 sub‐near isogenic lines (sub‐NILs). These sub‐NILs and controls were evaluated in field experiments grown under full and reduced irrigation treatments across 2 yr. Genotype × environment interactions were significant, so the data was separated into subsets of environments for further analyses. Significant QTL were detected for 20 trait–environment combinations. All QTL were partially or completely coincident. The presence of the S. habrochaites allele at QTL was associated with later maturity, lower yields, and greater WUE. However, yield and ∆13C exhibited no or low correlations with each other, suggesting these traits could be selected for improvement independently during breeding. Two of 21 sub‐NILs showed superior performance for WUE and yield compared to controls. These two genotypes may prove useful in breeding programs to improve the WUE of tomato cultivars without negative effects on yield.