bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improvement of glucocorticoid sensitivity and attenuation of pulmonary allergic reactions by exogenous supplementation with betaine in HDM and LPS‐induced allergic mouse model
Authors: Wang Qing , He Wen , Zhou Yufeng , Liu Yun , Li Xiaoling , Wang Yingwen , Wang Jiayu , Han Xiao , Zhang Xiaobo 
Published: February 2025

AbstractBackgroundChildhood asthma is a heterogeneous disease that exhibits different characteristics and varying severity; however, the metabolite alterations underlying the difference in asthma severity, especially in severe asthma, are not well understood. The aim of this study was to identify the plasma metabolic profile of children with different asthma severity and explore the potential intervention targets in severe asthma and glucocorticoid resistance.MethodsUntargeted liquid chromatography mass spectrometry was utilized to analyze plasma metabolites in 54 children with mild‐to‐moderate asthma, 50 children with severe asthma and 39 healthy controls. Multivariate statistical analyses were used to explore plasma metabolic alterations that were strongly associated with asthma severity. Meanwhile, the severe allergic airway inflammation mice with glucocorticoid resistance were constructed to validate the potential therapeutic capacity of metabolites.ResultsThe plasma metabolic profiles of children with mild to moderate asthma and severe asthma exhibited significant alterations. The distinct plasma metabolite shifts were accompanied by functional alterations in lipid metabolism, particularly choline metabolism, glycerophospholipids and sphingolipid metabolism. 11‐cis‐retinol, LysoPC (20:4 [8Z,11Z,14Z,17Z]), and glycerophosphatidylcholine were associated with exacerbated airway inflammation and lung function. Furthermore, 2‐Hydroxyestradiol, LysoPC (18:3 [6Z,9Z,12Z]), zeaxanthin, and betaine were shifted exclusively in the severe asthma group and may serve as potential biomarkers. Subsequent in vivo studies demonstrated that betaine supplementation partially improved glucocorticoid resistance.ConclusionsOverall, children with different asthma severity displayed distinct plasma metabolic patterns. These may contribute to the difference in response to glucocorticoids in childhood asthma and could be potential targets and interventions.
A phase 1 dose‐escalation study of LY3295668 erbumine as monotherapy and in combination with topotecan and cyclophosphamide in children with relapsed/refractory neuroblastoma
Authors: DuBois Steven G. , Ogawa Chitose , Moreno Lucas , Mossé Yaël P. , Fischer Matthias , Ryan Anne L. , Vo Kieuhoa T. , De Wilde Bram , Rubio‐San‐Simon Alba , Macy Margaret E. , Howell Lisa , Shusterman Suzanne , Corradini Nadège , Luksch Roberto , Aerts Isabelle , Foster Jennifer H. , Weiss Brian D. , Karthik Chandrasekhar Pamidipati , Yuen Eunice , Avsar Emin , Park Julie R. , Marachelian Araz 
Published: February 2025

AbstractBackgroundThis study evaluated the safety, pharmacokinetics, and antitumor activity of LY3295668 erbumine as monotherapy and combination therapy in children with relapsed/refractory neuroblastoma.MethodsPatients aged 2–21 years who had relapsed/refractory neuroblastoma were enrolled. LY3295668 erbumine was evaluated at two dose levels (12 and 15 mg/m2) and administered orally twice daily continuously as monotherapy and in combination with intravenous topotecan and cyclophosphamide in 28‐day cycles.ResultsTwenty‐five patients were treated. No dose‐limiting toxicity occurred in monotherapy; one patient had dose‐limiting toxicities in the combination therapy cohort (grade 3 mucositis and grade 4 neutropenia). The recommended phase 2 dose for both monotherapy and combination therapy was 15 mg/m2. Twenty‐two patients (88%) had one or more treatment‐related adverse event(s) (TRAEs), and 18 (72%) experienced grade ≥3 TRAEs. Myelosuppression was the most common high‐grade TRAE observed in the combination therapy cohort. At both dose levels, steady‐state plasma concentrations exceeded xenograft 90% inhibitory concentration levels. In the monotherapy cohort, one patient had a minor response, and one patient had stable disease, both continuing for >12 months. In the combination therapy cohort, two patients had a partial response, two had a minor response, and six had stable disease. Overall, the response rate, according to New Approaches to Neuroblastoma Therapy version 2.0 criteria, was 8%, and the disease control rate was 52%.ConclusionsLY3295668 erbumine had a manageable safety profile as monotherapy and in combination therapy. Although proof‐of‐concept clinical responses were observed, future studies with biomarker‐selected populations and/or novel combinations may yield higher response rates with Aurora kinase A inhibition.
ProACT: Probabilistic Analysis and Countermeasures Tool for Blockchain Supply Chains With Smart Contracts Composition
Authors: Manjula Rangu , Chauhan Naveen 
Published: February 2025

ABSTRACTThis study introduces the ProACT (Probabilistic Analysis and Countermeasures Tool) framework, which uses Bayesian Networks, Colored Petri Nets, and NuSMV (new symbolic model validator) to check and improve smart contracts in blockchain‐based supply chains. The main aim is to make smart contracts safer and more reliable in the Agrochem and Fertilizers Supply Chain. The research focuses on the need for better security in blockchain applications. There is a gap in current methods that handle the unpredictable nature of smart contracts. This study seeks to fill this gap with a new approach. The ProACT framework combines different models. Bayesian Networks help understand dependencies and uncertainties. Colored Petri Nets show how contracts change over time. NuSMV checks the contracts formally to find issues. The study includes a detailed case study and tests. Results show that ProACT is better at finding problems and checking contracts quickly. It also reduces the impact of attacks on the system. The findings are important because they offer a new way to make smart contracts safer. This helps improve the overall security of blockchain‐based supply chains.
Managing Clinical Research on Blockchain Using FAIR Principles
Authors: Cihan Seyma , Ozsoy Adnan , Beyan Oya Deniz 
Published: February 2025

ABSTRACTBlockchain technology has the potential to extend beyond its traditional use in cryptocurrency and make significant strides in critical sectors like healthcare. Clinical research, which plays a pivotal role in enhancing healthcare quality by guiding activities, determining equipment usage, and recommending preferred medications, stands to benefit greatly from blockchain integration. The unique technical capabilities of blockchain offer promising solutions across various phases of clinical research, from study design and patient recruitment to report study findings. By addressing current challenges in the clinical research process, blockchain technology can notably enhance research quality and, consequently, improve patient care. Although conceptual framework studies regarding blockchain technology are in the available literature, practical implementations of this technology remain relatively scarce. Thus, in this study, a private permissioned Hyperledger Fabric blockchain platform was developed to manage clinical research. As a use case, a blockchain‐based distributed framework for counting and reporting COVID‐19 epidemiological parameters and statistics among healthcare centers has been defined in the study. Besides, to make clinical research data findable, accessible, interoperable, and reusable (FAIR), we integrated FAIR principles into the developed blockchain‐based clinical research management system. Additionally, a use case logic has been implemented as a smart contract (chaincode) and invoked on Fabric Network. This study, in general, represents a crucial step towards bridging the gap between theoretical understanding and real‐world application within the domain of blockchain technology. Moreover, the performance of the Fabric Network was evaluated by analyzing the chain code execution performance according to the size of the patient data. By deploying a functioning clinical research network and executing smart contracts, this study contributes to the practical utilization of blockchain technology along with FAIR principles integration to the entire clinical research process, which is a first in the literature.
Numerical Analysis of the Effetcs of Blended Split Winglets on Aerodynamic Performance of Aircraft
Authors: Atasoy Ensar , Çuhadaroğlu Burhan 
Published: February 2025

ABSTRACTAir flows with different pressures on the upper and lower surfaces of a wing meet at the wing tip and trailing edge owing to the finite dimensions of the aircraft wings. As a result, wing tip vortices are formed, which increase the induced drag and reduce the aerodynamic performance of the wing. In this study, inspired by bird wings, we aim to design a winglet that reduces wing‐tip vortices using a biomimicry method. To verify the numerical method, the ONERA M6 wing, on which experimental and numerical studies were conducted by NASA, is used. The flow around the ONERA M6 wing is modeled using SOLIDWORKS software. The flow region around the wing, whose solid model is created, is divided into finite volumes using the ANSYS Fluent software. To verify the numerical model, a verification analysis is conducted on the pressure coefficient changes using experimental conditions in the literature. After the verification study, computations are performed at various angles of attack for the NACA 4412 winglet profile, which is added to the tip of the ONERA M6 wing at a sweep angle of 60° and different cant angles. The geometric configuration that provides the highest value for the aerodynamic performance parameter known as the lift coefficient to drag coefficient ratio (CL/CD) is determined. The results obtained from the study show that the highest CL/CD is obtained for the flow at 3.06° angle of attack and 15° cant angle winglet. Moreover, it is also calculated that the blended split winglet design, in which the upper winglet is designed to be longer with a 15° cant angle and the lower winglet to be shorter with a −30° cant angle, provides a 24.6% improvement in the CL/CD compared to the base wing.
Multi‐Objective Workflow Scheduling in Cloud Using Archimedes Optimization Algorithm
Authors: Kushwaha Shweta , Shankar Singh Ravi , Prajapati Kanika 
Published: February 2025

ABSTRACTCloud computing has changed the technology landscape for over a decade and led to an astounding growth in the number of applications it may be used for. Consequently, there has been a significant spike in the demand for improved algorithms to schedule workflows efficiently. These were mostly concerned with heuristic, metaheuristic, and hybrid approaches to workflow scheduling that mostly suffer from the problem of local optima entrapment. Due to such heavy traffic on the cloud resources, there is still a need for less computationally complex approaches. In light of this, this article proposes a novel approach: a multi‐objective Modified Local Escaping Archimedes Optimization (MLEAO) algorithm for workflow scheduling. This strategy involves initialization of the population of Archimedes Optimization algorithm through the HEFT algorithm to provide an inclination towards the solutions with improved makespan while achieving a cost‐efficient workflow scheduling decision and avoiding the problem of local optima entrapment using a local escaping operation. To validate the efficacy of our approach, we conducted extensive experiments using scientific workflows as benchmarks. Through our investigations, we significantly improved makespan, cost, resource utilization, and energy consumption. Moreover, the effectiveness of our proposed approach is also verified by performance metrics such as hypervolume, s‐metric, and dominance relationships between the proposed and state‐of‐the‐art approaches.
Photophysical and Time‐resolved Infrared Properties of Long‐Lived Rhenium(I) 4,5‐Diazafluorene Tricarbonyl Chromophores
Authors: Alameh Reem T. , Rosko Michael C. , Danilov Evgeny O. , Durand Nicolas , Castellano Felix N. 
Published: February 2025

AbstractThis report investigates the synthesis, structural characterization, fundamental molecular photophysics, electrochemistry, UV‐Vis spectroelectrochemistry, and time‐resolved infrared spectroscopic properties of eight [fac‐Re(dafR)(CO)3L]0/+ complexes, where R=ethyl [(dedaf); 1, 3, 5, 7] or H [(dafH); 2, 4, 6, 8] and L=Cl− (1, 2), imidazole [(Im); 3, 4], 4‐ethylpyridine [(4‐Etpy); 5, 6], or pyridine [(py); 7, 8]. Universally, 1–8 yield higher energy photoluminescence (PL) emission bands and higher PL quantum yields (up to 53 %) than the classic 2,2’‐bipyridine (bpy) and 1,10‐phenanthroline (phen) ligated Re(I) tricarbonyl complexes. The excited state lifetimes of 1–8 lie between those corresponding to the bpy and phen derivatives, ranging from 120 and 1300 ns at room temperature. Combinations of reductive UV‐Vis spectroelectrochemistry, transient absorption spectroscopy, and time‐resolved infrared spectroscopy consistently assigned the lowest excited states in 1–8 being of metal‐to‐ligand charge transfer (MLCT) character. These new ReI MLCT chromophores follow classic energy gap law behavior and possess the characteristics necessary for serving as valuable photosensitizers suitable to energize excited state electron and energy transfer photochemistry.
Sustainable One‐Pot Electrochemical Approach for Entrapment of Multi‐Enzymes and Biocompatible Redox Mediator
Authors: Seelajaroen Hathaichanok , Mayr Felix , Wielend Dominik , Cobet Munise , Ulbricht Christoph , Serdar Sariciftci Niyazi , Tekoglu Serpil 
Published: February 2025

AbstractEnzyme immobilization is regarded as a key factor for their effective utilization in various fields such as biofuel production, wastewater treatment, and biosensors. Designing new electrodes with biocompatible support matrices is essential to improve the stability in bioelectrocatalysis. Modified carbon felt electrodes were prepared and tested as bioelectrocatalyst under mild conditions – aqueous media at room temperature and basically neutral pH. Co‐immobilization of dehydrogenase enzymes and neutral red (NR) dye at carbon felt electrodes was successfully achieved during electropolymerization of pyrrole in a facile one‐step approach. Neutral red was incorporated to operate as a redox mediator supporting efficient electron transfer to the enzymes’ active sites. Electrodes modified with alcohol dehydrogenase (ADH) have been employed to reduce acetaldehyde to ethanol in a chronoamperometic setting with Faradaic efficiency (FE) of up to 33 %. By incorporating the cascade reaction with three enzymes – ADH, formate dehydrogenase, and formaldehyde dehydrogenase – an electroreduction sequence could be established to produce methanol from CO2 reaching a FE of 10 %. The proposed approach shows good stability. Together with the simple implementation and application, this process is promising for employment in enzymatic electrocatalysis.
Exploring differentially expressed genes and associated biological processes across embryos with different seed dormancy in barley (Hordeum vulgare)
Authors: Aoyagi Blue Yuta , Hirakawa Hideki , Oono Youko , Nakamura Shingo 
Published: February 2025

AbstractBarley (Hordeum vulgare) has a wide range of seed dormancy. Seed dormancy is a crucial trait for plant survival and crop production. To explore genes and functions associated with the difference in barley seed dormancy, we performed differentially expressed gene and gene ontology (GO) enrichment analyses on seed embryos from a wild barley accession H602 with strong dormancy, a cultivated malting barley accession Kanto Nakate Gold (KNG) with weak dormancy, and reciprocal crosses between the two H602 × KNG and KNG × H602. RNA was extracted from embryos in seeds harvested at physiological maturity and dried for 1 week. We also assessed expression levels of known quantitative trait locus genes linked to seed dormancy. In H602 and H602 × KNG, 417 genes showed significantly higher expression than KNG and KNG × H602, with 14 GO terms enriched, including stress response and sugar metabolism. Genes involved in DNA repair were also enriched for highly expressed genes in H602 than KNG. In KNG and KNG × H602, 198 genes showed significantly higher expression than H602 and H602 × KNG, with 60 GO terms enriched, including development and auxin transport. Genes involved in translation were also enriched for highly expressed genes in KNG × H602 than H602 × KNG. Our findings indicated that genes involved in abiotic stress response, sugar metabolism, and DNA repair would be associated with strong seed dormancy, whereas genes involved in development and translation would be associated with weak dormancy in barley.
Grape Stalks Valorization towards Circular Economy: A Cascade Biorefinery Strategy
Authors: Valle Carlotta , Grillo Giorgio , Calcio Gaudino Emanuela , Ponsetto Paola , Mazzoli Roberto , Bonavita Giulia , Vitale Pietro , Pessione Enrica , Garcia‐Moruno Emilia , Costantini Antonella , Cravotto Giancarlo , Tabasso Silvia 
Published: February 2025

AbstractLignocellulosic biomasses have the potential to generate by‐products with biological activity (i. e., polyphenols) as well as biopolymers (i. e., cellulose, hemicellulose, pectins, lignin). The wine industry is one of the pillars of Italian agri‐food sector. Nevertheless, large quantities of by‐products such as grape stems are produced, which are usually disposed of at a cost, and therefore represent an attractive negative‐cost feedstock for biorefinery. In this work, a sequential protocol for biomass valorization is proposed, characterized by a multidisciplinary strategy using enabling technologies and subcritical water as a green solvent, where physical/chemical treatments synergistically interact with biological treatments. The first phase involved the sequential fractionation of grape stalks, obtaining several product streams rich in polyphenols, hemicellulose, pectin (13.15 % of cumulative yield on biomass), lignin and cellulose. A membrane treatment was employed to recycle materials within the process. Finally, the cellulose‐rich residue was exploited as a fermentation substrate for the last step, producing up to 5.8 g/L of lactic acid by harnessing suitably engineered Clostridium thermocellum strains. The polyphenolic fraction successfully inhibited the growth of Brettanomyces bruxellensis and Acetobacter pasteurianus, microorganisms responsible for major wine off‐flavors. Globally, this study represents a proof‐of‐concept of a second‐generation biorefining process based on locally available waste biomass.
AGORA: Adaptive Generation of Orthogonal Rational Approximations for Frequency‐Response Data
Authors: Lemus Andria , Ege Engin Arif 
Published: February 2025

ABSTRACTThis paper introduces the adaptive generation of orthogonal rational approximations (AGORA) method for rational function approximation of measured or simulated microwave network parameters. The output of AGORA is a state‐space model or a rational function model that is representative of the input data. The generated model can then be used to interpolate the data or to evaluate the data quality. A typical application is the time‐domain signal and power integrity analysis in circuit simulations using the generated model from measured or simulated interconnnects and power distribution networks. AGORA allows estimating the model order for a given error tolerance and does not require any initial estimates or adjustment of hyperparameters.
N6‐Methyladenosine modification mediated by METTL3 promotes DNA‐PKcs expression to induce anlotinib resistance in osteosarcoma
Authors: Zhang Yining , Shen Guohong , Zhang Dan , Meng Tingting , Lv Zhaorui , Chen Lei , Li Jianmin , Li Ka 
Published: February 2025

ABSTRACTBackgroundAcquired anlotinib resistance is still a key challenge in osteosarcoma treatment. Unravelling the mechanisms underlying anlotinib resistance is the key to optimising its efficacy for treating osteosarcoma. Previous studies have explored the pivotal function of the DNA‐dependent protein kinase catalytic subunit (DNA‐PKcs) with regard to osteosarcoma chemoresistance.MethodsWe used bioinformatics analysis to predict DNA‐PKcs and Beclin‐1 interactions, confirmed through immunofluorescence (IF) and co‐immunoprecipitation (co‐IP). Dual‐luciferase analyses and Methylated RNA immunoprecipitation (MeRIP) were implemented to detect the detected m6A modifications. RNA fluorescence in situ hybridisation (FISH)—IF co‐localisation and RNA immunoprecipitation (RIP) were conducted to explore the interplay between PRKDC mRNA and the indicated proteins.ResultsAnlotinib‐treated osteosarcoma cells exhibited increased DNA‐PKcs levels, and silencing DNA‐PKcs augmented osteosarcoma sensitivity to anlotinib. DNA‐PKcs affects anlotinib‐induced autophagy by interacting with Beclin‐1 and regulating its ubiquitination. Notably, PRKDC mRNA, encoding DNA‐PKcs, underwent N6‐Methyladenosine (m6A) modification. Methyltransferase‐like 3 (METTL3) positively regulated DNA‐PKcs expression. Functionally, METTL3 enhances anlotinib resistance in osteosarcoma, which is reversed by PRKDC knockdown. Mechanistically, METTL3 binds to PRKDC mRNA and facilitates m6A methylation. Additionally, m6A methylated PRKDC mRNA is identified via YTH N6‐methyladenosine RNA‐binding protein 1 (YTHDF1), augmenting its expression.ConclusionThese findings revealed that DNA‐PKcs promotes anlotinib resistance by regulating protective autophagy, while METTL3 induces PRKDC m6A modification, enhancing its expression. Thus, targeting METTL3/PRKDC may be a novel strategy for improving therapeutic efficacy in human osteosarcoma.Key points
DNA‐PKcs knockdown heightens osteosarcoma sensitivity to anlotinib.
DNA‐PKcs modulates anlotinib‐induced protective autophagy through interacts with Beclin‐1 and regulates its ubiquitination.
m6A modification of OLE_LINK82PRKDC mRNA induced by METTL3 contributes to anlotinib resistance in osteosarcoma.
m6A methylation of PRKDC mRNA recognised by YTHDF1 amplifies the expression of DNA‐PKcs.
Unraveling the Role of Repurposed Drugs in the Treatment of Acne: Success so Far and the Road Ahead
Authors: Kumbhar Popat S. , Kamble Vikas , Kolekar Kaustubh Ajit , Vishwas Sukriti , Kumbhar Pranav , Patil Kalpana S. , Gupta Gaurav , Kharabe Pankaj M. , Singh Manisha , Gurav Shailendra , Chellappan Dinesh Kumar , Singh Sachin Kumar , Dua Kamal , Disouza John , Patravale Vandana 
Published: February 2025

ABSTRACTAcne is a skin disease that impacts 9.4% of the world's population. Available treatments for managing acne include retinoid‐like drugs, antibiotics, corticosteroids, photo, and radiotherapy. Howevere, the aforementioned treatments have certain limitations such as possibility of developing skin cancer from tetracycline, doxycycline, and corticosteroids, microbial resistance to antibiotics, and deadly side effects, and so forth. Repurposing of existing therapeutics having excellent safety profile can be promising way to treat acne efficiently. The repurposed drugs and phytoceuticals from diverse classes have demonstrated promising effects in treating acne. These repurposed drugs have displayed antiacne effectiveness by targeting single or multiple signaling pathways. Various repurposed therapeutics undergoing clinical trials at different phases demonstrated their safety and efficacy in treating acne. Despite being a very good, safe, and less time‐consuming strategy, drug repurposing (DR) faces multiple challenges such as lack of regulatory guidelines, preservation of intellectual property, and clinical validation of claimed therapeutic indication. DR appears to be a viable approach and is likely to offer effective treatment at a reasonable cost in alleviating acne.