bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methods to Characterise Enzyme Kinetics with Biological and Medicinal Substrates: The Case of Alkaline Phosphatase
Authors: Harroun Scott G. , Vallée‐Bélisle Alexis 
Published: July 2023

AbstractAlkaline phosphatase (AP) enzymes are of broad interest in fields ranging from biochemistry and medicine to biotechnology and nanotechnology. Characterising the catalytic activity of AP is typically realised by either employing non‐natural signal‐generating substrates that are detectable by absorbance and fluorescence spectroscopy or by quantifying the release of inorganic phosphate by the classic malachite green assay. The latter method is often required for studying “spectroscopically silent” biomolecular substrates, but it does not enable continuous monitoring of kinetics in real‐time. In recent years, newer techniques for studying AP function have been developed to circumvent this limitation, including fluorescent and colourimetric substrate‐specific assays based on supramolecular chemistry, organic probes and nanomaterials, as well as other assays based on isothermal titration calorimetry, direct detection with infrared spectroscopy and mass spectrometry, and monitoring conformational change by fluorescent nanoantennas. Here, we review these strategies and comment on their strengths and weaknesses in the context of AP.
Versa DB: Assisting 13C NMR and MS/MS Joint Data Annotation Through On‐Demand Databases
Authors: Cordonnier Julien , Remy Simon , Renault Jean‐Hugues , Nuzillard Jean‐Marc 
Published: July 2023

AbstractCompound identification in complex mixtures by NMR and MS is best achieved through experimental databases (DB) mining. Experimental DB frequently show limitations regarding their completeness, availability or data quality, thus making predicted database of increasing common use. Querying large databases may lead to select unlikely structure candidates. Two approaches to dereplication are thus possible: filtering of a large DB before search or scoring of the results after a large scale search. The present work relies on the former approach. As far as we know, nmrshiftdb2 is the only open‐source 13NMR chemical shift predictor that can be freely operated in batch mode. CFM‐ID 4.0 is one of the best‐performing open‐source tools for ESI‐MS/MS spectra prediction. LOTUS is a freely usable and comprehensive collection of secondary metabolites. Integrating the open source database and software LOTUS, CFM‐ID, and nmrshiftdb2 in a dereplication workflow requires presently programming skills, owing to the diversity of data encoding and processing procedures. A graphical user interface that integrates seamlessly chemical structure collection, spectral data prediction and database building still does not exist, as far as we know. The present work proposes a stand–alone software tool that assists the identification of mixture components in a simple way.
Camera traps reveal that terrestrial predators are pervasive at riverscape cold‐water thermal refuges
Authors: Sullivan Christopher J. , Rittenhouse Chadwick D. , Vokoun Jason C. 
Published: July 2023

AbstractPerceived predation risks by terrestrial predators are major ecological forces in aquatic systems, particularly for aggregating fish. Riverscape thermal refuges are discrete, localized cold‐water patches where fish temporarily aggregate to buffer against heat events. Predation pressures by terrestrial predators at thermal refuges may decrease the thermoregulatory benefits of refuge use, but quantifying such effects can be challenging and controversial when sampling can impose additional stress on fish. We passively monitored terrestrial predator visitation patterns and predation at four thermal refuges in the Housatonic River, Connecticut, USA, between May 18th and September 29th, 2022, with camera traps, a common wildlife monitoring method. Specifically, we (1) assessed diel visitation patterns by different categories of terrestrial predators at thermal refuges and determined if patterns varied among predator categories or with prevailing environmental conditions, and (2) estimated the probability of predation by hour of the day combined across all predator categories, quantifying general predation pressures at refuges. We detected at least one terrestrial predator at a thermal refuge each day, and mean hourly visitation rates (count/h) were highly variable across predator categories and sampling dates. The most supported generalized additive mixed model indicated that terrestrial predator visitation rates (count/h/day) varied with mean daily river discharge and water temperature differential, and relationships differed across categories of terrestrial predators. We observed 22 separate predation attempts on thermoregulating salmonids and predicted that the probability of predation by any terrestrial predator increased from 0.002 to 0.017 throughout a 24 h day (p = .004). Camera traps provided novel evidence that terrestrial predators are pervasive at riverine thermal refuges, which is relevant for refuge conservation and management globally. We recommend the implementation of a coordinated monitoring network across riverine thermal refuges using camera traps, further enriching our ecological understanding of cumulative predator effects in refuges across complex riverscapes.
Temperature dependence ofESDeffects on 28 nmFD‐SOI MOSFETs
Authors: Xiao Yiping , Liu Chaoming , Zhang Yanqing , Qi Chunhua , Ma Guoliang , Wang Tianqi , Huo Mingxue 
Published: July 2023

AbstractThe failure mechanisms caused by electrostatic discharge (ESD) effects at ambient temperatures ranging from −75 to 125°C are investigated by Silvaco TCAD simulator. The devices are NMOS transistors fabricated with 28 nm fully depleted silicon‐on‐insulator (FDSOI) technology. Results indicate that with an increase in temperature, the first breakdown voltage of the device decreased by 27.32%, while the holding voltage decreased by approximately 8.49%. The total current density, lattice temperature, potential, and so forth were extracted for a detailed insight into the failure process. These findings provide valuable references for the design and development of ESD protection devices applied at different temperature ranges.
Impact of endorsement policy on the performance of blockchain‐based VANET
Authors: Gaba Priyanka , Raw Ram Shringar 
Published: July 2023

AbstractWith the revolution in technology, VANET has emerged as a new generation of technology and used globally for intelligent traffic management systems. VANET uses a PKI‐based protocol to maintain privacy and security. Still, some crucial issues remain unresolved, like blind belief in communicated messages, lack of vehicle's interest in participation, revealing the sender vehicle's identity, and maintaining integrity. The solution to these issues will prevent vehicles from propagating fake messages while concurrently protecting the confidentiality of each involved vehicle against tracking attacks. Blockchain, a peer‐to‐peer, immutable, distributed ledger‐based technology, can be adapted as a robust solution to overcome critical challenges and make VANET more secure and reliable. This paper proposes a novel blockchain‐based VANET architecture, blockchain‐based vehicular ad‐hoc network (B‐VANET), implemented on the Hyperledger Fabric platform. B‐VANET aims to secure the network by validating road events before actually updating it on the network. For validation, the trust factor of each vehicle and their past involvement in the network is maintained. Trust factor value decides the trustworthiness of a vehicle. Based on this trust factor, a dynamic endorsement policy is designed. Endorsement policy, part of the smart contract, plays a vibrant role in Hyperledger Fabric. It decides how many and which particular peers can endorse the transaction to make it valid and add it to the ledger. Multiple possible approaches to endorsement policies are identified for B‐VANET and are analyzed using the Hyperledger Caliper tool. These approaches are evaluated for data integrity, confidentiality, and real‐time system issues. An appropriate approach for the B‐VANET system is recognized, giving the best throughput and latency in all possible scenarios. It is analyzed that compared to the worst approach, the best approach achieves an almost 15% increase in throughput and reduces latency by nearly half. We also compared the performance of B‐VANET and other approaches to show that our proposed system better meets VANET's security needs.
A coupled SPH‐EBG numerical model for deformations of MCF7 cancer cell in a microchannel flow
Authors: Lee Jia Min , Chan Wai Lee 
Published: July 2023

SummaryProperties of a cell can determine its deformations, which can aggravate cancer metastasis. In laboratory, microfluidic technology has been adopted to study cell deformations. However, quantifying the effects of cell deformations has remained difficult. To this end, this paper presents a two‐dimensional particle‐based model that can capture flow‐induced cell deformations in a microchannel. The numerical model is validated with an experimental dataset for MCF7 cell. The simulations show that cell deformations are dominantly attributed to flow acceleration. Stress analyses, conducted by inputting the simulated cell deformations as boundary conditions, show that the maximum normal stresses correspond well to high deformations. Shear stress is in general proportional to the cell's distance from a wall. The simulations also suggest a deformed cell shape that apparently may reduce the average normal stresses. This study highlights the potential of the numerical model to relate the measurable cell deformations to the more elusive cell properties.
Ionizing radiation promotes, whereas calorie restriction suppresses, NASH and hepatocellular carcinoma in mice
Authors: Shang Yi , Morioka Takamitsu , Daino Kazuhiro , Nakayama Takafumi , Nishimura Mayumi , Kakinuma Shizuko 
Published: July 2023

AbstractThe pathological conditions of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH) are the major risk factors for hepatocellular carcinoma (HCC). Exposure to DNA‐damaging agents such as ionizing radiation is another risk factor for HCC; calorie restriction (CR), however, effectively delays the onset of radiation‐induced HCC. We investigated whether NASH is relevant to radiation‐induced HCC and the cancer‐preventing effect of CR. Eight‐day‐old male B6C3F1 mice were irradiated with 3.8 Gy of X‐rays and then fed a standard diet or 30% CR diet from 49 days of age until necropsy, which was performed from 56 to 600 days with ~100‐day intervals to assess both pathological changes and gene expression levels. We found that early‐life exposure to radiation accelerated lipid accumulation and NASH‐like histopathological changes in the liver, accompanied by accelerated development of HCC. CR ameliorated the changes in lipid metabolism in the liver and reversed the NASH‐like pathology, which effectively delayed HCC development. Gene‐expression profiling revealed the radiation‐related activation and CR‐related suppression of the peroxisome proliferator‐activated receptor gamma/Cd36 pathway of transmembrane fatty‐acid translocation before development of the NASH‐like state. Thus, early‐life exposure to radiation affects lipid metabolism and induces a steatoinflammatory microenvironment that favors HCC development. Therefore, targeting this pathway by CR (or measures that mimic CR) may be a promising strategy for preventing HCC caused by either radiation or other DNA‐damaging agents.
Muscone attenuates susceptibility to ventricular arrhythmia by inhibiting NLRP3 inflammasome activation in rats after myocardial infarction
Authors: Yang Shuang , Bi Yingying , Wei Yanzhao , Li Wei , Liu Jiangwen , Mao Tuohua , Tang Yanhong 
Published: July 2023

AbstractFibrosis and abnormal expression of connexin 43 (Cx43) in the ventricle play vital roles in ventricular arrhythmias (VAs) after myocardial infarction (MI). Muscone, an active monomer of heart‐protecting musk pill, has various biological activities, but its effect on susceptibility to VAs in rats with MI has not been determined. In the present study, we investigated the effects of muscone on ventricular inflammation, fibrosis, Cx43 expression, and the occurrence of VAs after MI. An MI model was established by ligating the proximal left anterior descending coronary artery. Then, the MI model rats were administered muscone (2 mg/kg/day) or vehicle (saline)via intragastric injection for 14 days. Cardiac function was evaluated by echocardiography, and an in vivo electrophysiological study was performed on Day 14. Cardiac inflammation, fibrosis, and Cx43 expression were determined by histochemical analysis and western blot analysis. Our results indicated that muscone treatment significantly improved cardiac function and inhibited ventricular inflammation, fibrosis, and nucleotide‐binding oligomerization domain, leucine‐rich repeat, and pyrin domain containing 3 (NLRP3) inflammasome activation. Electrocardiogrphy and electrophysiology studies showed that muscone shortened the QRS interval, QT interval, QTc interval, and action potential duration; prolonged the effective refractory period; and reduced susceptibility to VAs in rats after MI. Furthermore, Cx43 expression in the BZ was increased by muscone treatment, and this change was coupled by inhibition of the NLRP3/IL‐1β/p38 MAPK pathway. Taken together, our results demonstrated that muscone reduces susceptibility to VA, mainly by decreasing ventricular inflammation and fibrosis, and attenuates abnormal Cx43 expression by inhibiting NLRP3 inflammasome activation after myocardial infarction in rats.
The New S7B/E14 Q&A Document Provides Additional Opportunities to Replace the Thorough QT Study
Authors: Darpo Borje , Leishman Derek J. 
Published: July 2023

AbstractSince 2015, concentration–QTc (C–QTc) analysis has been used to exclude the possibility that a drug has a concerning effect on the QTc interval. This has enabled the replacement of the designated thorough QT (TQT) study with serial electrocardiograms (ECGs) in routine clinical pharmacology studies, such as the first‐in‐human (FIH) study. The E14 revision has led to an increased proportion of FIH studies with the added objective of QT evaluation, with the intention of replacing the TQT study. With the more recent revision of the S7B/E14 Q&A document in February 2022, nonclinical assays/studies can be brought into the process of regulatory decisions at the time of marketing application. If the hERG (human ether‐a‐go‐go‐related gene) and the non‐rodent in vivo study are conducted according to the described best practices and are negative, the previous requirement that a QTc effect of >10 milliseconds must be excluded in healthy subjects at plasma concentrations 2‐fold above what can be seen in patients can be reduced to covering the concentrations seen in patients. For drugs that cannot be safely given in high doses to healthy subjects, ECG evaluation is often performed at the therapeutic dose in patients. If a QTc effect of >10 milliseconds can be excluded, an argument can be made that the drug should be considered as having a low likelihood of proarrhythmic effects due to delayedrepolarization, if supported by negative best practices hERG and in vivo studies. In this article, we describe what clinicians involved in early clinical development need to understand in terms of the hERG and in vivo studies to determine whether these meet best practices and therefore can be used in an integrated clinical/nonclinical QT/QTc risk assessment.
Early family socioeconomic status and later leadership role occupancy: A multisource lifespan study
Authors: Barling Julian , Granger Steve , Weatherhead Julie G. , Turner Nick , Pupco Shani 
Published: July 2023

SummaryWe investigate the indirect effects of socioeconomic status, both at birth and at age 5, on the likelihood of holding a formal leadership position 26 years later via two sequential mechanisms: children's self‐control at age 10 and adolescents' psychological well‐being at age 16. We test this model using multisource data from the British Cohort Study, an ongoing research project studying individuals born in England, Scotland, and Wales in the week of April 5–11, 1970. The data were collected at five different time points, from birth through early adulthood. Results show that the cumulative effects of early socioeconomic status predict children's self‐control at age 10, and self‐control in turn predicts a higher likelihood of leadership role occupancy at age 26 via psychological well‐being at age 16. The findings of the current study illustrate how a range of individual and family factors measured across the lifespan predict leadership role occupancy, with implications for better understanding how socioeconomic adversity and privilege enhance individuals' likelihood of becoming leaders early in their careers.
Unravelling social barriers in ecological restoration decision‐making: A network analysis approach
Authors: Mañas‐Navarro José Javier , Aledo Antonio , Ortiz Guadalupe , Cortina‐Segarra Jordi 
Published: July 2023

AbstractEcological restoration (ER hereafter) is situated within a complex socio‐political landscape, characterized by competing interests that can hinder effective decision‐making and implementation of ER initiatives. Despite its importance, these social factors influencing ER decision‐making processes have not been comprehensively examined or interconnected in a systemic manner. This research aims to identify and systematically analyse the social barriers that obstruct ER decision‐making processes in the case of the Valencian Autonomous Region, Spain. Employing a qualitative methodological approach, this study utilized causal maps and network analysis to create a systemic representation of social barriers impacting ER, as identified by the key actors involved in the decision‐making process. The findings establish a relational model of social barriers that influence ER decision‐making. Central nodes of the process, as revealed by this network analysis, include the lack of private sector interest in ER initiatives, the excessive electoral motivation of political decisions and the inefficient civil service structure. This research contributes to a better understanding of the socio‐political dimensions of ER and provides valuable insights for overcoming barriers in the decision‐making process.
Differentiation characteristics of karst vegetation resilience and its response to climate and ecological restoration projects
Authors: Tiantian Chen , Qiang Wang , Yuxi Wang , Li Peng 
Published: July 2023

AbstractIn light of the recent pressure from global warming, extreme drought events, and deleterious human activity, the strength and long‐term change trends of vegetation in karst regions—in terms of their resistance to external disturbances—have not been studied systematically. Therefore, herein, we quantified the vegetation resilience and its nonlinear change trends in south China karst under different environmental gradients by measuring the lag‐1 autocorrelation to time‐series Normalized Difference Vegetation Index (1990–2018), clarifying the driving forces of vegetation resilience changes. It was shown that the vegetation resilience change in south China karst was not monotonous. In the first stage (pre‐2002), precipitation and warming promoted the increase of regional vegetation resilience (slope = −0.045, p < 0.0001). In the second stage (during 2002–2010), the increasing trend of vegetation resilience was not obvious and vegetation resilience was difficult to keep up with vegetation productivity, indicating the time‐lagged effect of ecological restoration projects to vegetation resilience. In the third stage (post‐2010), due to the continuous advancement of ecological restoration projects, vegetation resilience increased significantly and had the largest amplitude (slope = −0.128, p < 0.0001). Simultaneously, under different environmental gradients, vegetation resilience showed significant differentiation characteristics. In comparison to non‐karst regions, increases in the vegetation resilience were more obvious in karst regions especially in the post‐2010. With increases in the soil depth, the vegetation resilience exhibited an increasing trend, indicating its dependence on soil. At slopes >25°, the vegetation resilience increased most obviously and the resilience of meadows was the largest, which can be the preferred vegetation type for ecological restoration projects. This research provides another perspective to understand karst vegetation ecosystem and the results will facilitate the protection of karst ecosystems.
Isolation and functional analysis of phage‐displayed antibody fragments targeting the staphylococcal superantigen‐like proteins
Authors: Alanko Ida , Sandberg Rebecca , Brockmann Eeva‐Christine , de Haas Carla J. C. , van Strijp Jos A. G. , Lamminmäki Urpo , Salo‐Ahen Outi M. H. 
Published: July 2023

AbstractStaphylococcus aureus produces numerous virulence factors that manipulate the immune system, helping the bacteria avoid phagocytosis. In this study, we are investigating three immune evasion molecules called the staphylococcal superantigen‐like proteins 1, 5, and 10 (SSL1, SSL5, and SSL10). All three SSLs inhibit vital host immune processes and contribute to S. aureus immune evasion. This study aimed to identify single‐chain variable fragment (scFvs) antibodies from synthetic antibody phage libraries, which can recognize either of the three SSLs and could block the interaction between the SSLs and their respective human targets. The antibodies were isolated after three rounds of panning against SSL1, SSL5, and SSL10, and their ability to bind to the SSLs was studied using a time‐resolved fluorescence‐based immunoassay. We successfully obtained altogether 44 unique clones displaying binding activity to either SSL1, SSL5, or SSL10. The capability of the SSL‐recognizing scFvs to inhibit the SSLs' function was tested in an MMP9 enzymatic activity assay, a P‐selectin glycoprotein ligand 1 competitive binding assay, and an IgG1‐mediated phagocytosis assay. We could show that one scFv was able to inhibit SSL1 and maintain MMP9 activity in a concentration‐dependent manner. Finally, the structure of this inhibiting scFv was modeled and used to create putative scFv‐SSL1‐complex models by protein–protein docking. The complex models were subjected to a 100‐ns molecular dynamics simulation to assess the possible binding mode of the antibody.
Association of m1A modification gene polymorphisms with glioma risk in Chinese children
Authors: Liao Fan , Hua Rui‐Xi , Jia Xingyu , Liao Yuxiang , Yuan Li , Ruan Jichen , Li Tianfeng , Zhuo Zhenjian , He Jing 
Published: July 2023

AbstractGlioma is a highly heterogeneous malignancy with a high mortality rate and poor prognosis. m1A methylation modifications are associated with gliomagenesis. However, whether single nucleotide polymorphisms (SNPs) of m1A modification genes are associated with glioma risk is unclear. We successfully genotyped 20 SNPs of m1A‐modified genes TRMT10C, TRMT61B, TRMT6, TRM61, ALKBH1, YTHDC1, YTHDF1, and YTHDF2 in 314 pediatric glioma patients and 380 cancer‐free controls using TaqMan probes. Associations of polymorphisms with glioma risk were assessed by the odds ratios and 95% confidence intervals generated by logistic regression models. Stratified analysis was performed by age, gender, tumor subtype, and clinical stage. The results showed that TRMT10C rs2303476, TRMT10C rs4257518, TRM61 rs2296484, and YTHDF2 rs3738067 polymorphisms were significantly associated with an increased risk of glioma, TRMT61B rs4563180, YTHDC1 rs2293595, and YTHDC1 rs3813832 polymorphisms were significantly associated with a reduced risk of glioma. In addition, analysis of the expression quantitative trait loci‐showed that the TRM61 rs2296484 T allele significantly increased TRM61 messenger RNA (mRNA) expression, the YTHDF2 rs3738067 G allele significantly increased YTHDF2 mRNA expression, and the TRMT61B rs4563180 C allele significantly decreased TRMT61B mRNA expression. Overall, we identified several promising candidates for m1A modification gene polymorphisms as biomarkers of glioma risk.