bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutic Insights into Alkanna tinctoria Phytochemicals as Cholinesterase Inhibitor for Alzheimer’s Disease
Authors: Ashraf Sidra , Khan Muhammad Umer , Shafi Abeeha , Eltaib Lina , Shabbir Chaudhry Ahmed , Alzahrani Abdullah R. , . Abida , Imran Mohd
Published: February 2025

Alzheimer's disease (AD) poses a substantial challenge in the management of neurodegenerative disorders, necessitating innovative therapeutic strategies. Previous studies indicated that dual‐target cholinesterase inhibitors, which obstruct both AChE and BuChE, may offer therapeutic advantages in Alzheimer's disease.
This study aimed to determine the potential contribution of cholinesterase inhibitory activity of phytocompounds derived from Alkanna tinctoria as prospective anti‐Alzheimer agents. We employed an in silico docking methodology to investigate the cholinesterase inhibitory activity of Alkanna tinctoria extracts. The present study revealed that flavonoid derivatives, specifically kaempferol‐3‐rutinoside and quercetin‐3‐glucopyranoside, exhibited considerable inhibitory effects on AChE, with docking scores of (‐13.233 kcal/mol) and (‐12.566 kcal/mol), respectively, and on BuChE, with docking scores of (‐11.827 kcal/mol) and (‐11.529 kcal/mol), in comparison to conventional Alzheimer's disease treatments (Donepezil & Huprine19). The compounds were further assessed for pharmacokinetic characteristics and toxicity, demonstrating favorable ADMET profiles indicative of high oral bioavailability and low toxicity, which are crucial for therapeutic use. Molecular Dynamics (MD) simulations further corroborated the robustness of these ligand‐enzyme interactions, demonstrating their stability over time and enhancing their potential for prolonged utilization. These compounds initiated pathways for viable in vitro/in vivo experiments to determine the clinical effectiveness of these medicines.
Prevalence of Aspirin Resistance in Patients with Transcatheter Pulmonary Valve Replacement
Authors: Sigman Alex , Riley Emily , Pierick Trudy , Aldoss Osamah , Porayette Prashob
Published: February 2025

Background

Congenital heart disease (CHD) patients with pulmonary valve failure may undergo transcatheter pulmonary valve replacement (TPVR). Aspirin is often prescribed as long‐term therapy after TPVR to prevent thromboembolic events (TE).

Aims

We aimed to examine the prevalence of aspirin resistance within the CHD TPVR population.

Methods

The VerifyNow point‐of‐care test quantifies platelet aggregation as Aspirin Reactivity Units (ARU). ARU values greater than 550 suggest aspirin resistance (AR). A retrospective chart review analyzed ARU test results from May 2022 through December 2023 in CHD patients following successful TPVR (n = 48). Lifelong TE history was collected. Association between AR and sex, race, and ethnicity was examined with Fisher's Exact test, and the Wilcoxon rank sum exact test analyzed associations between AR and age.

Results

Three of 45 (6.67%) CHD TPVR aspirin‐compliant patients (average age 33.14 years; range 0.74−77.86 years, 47% females) were AR. Interestingly, all AR patients were females, suggesting higher AR prevalence in females (p = 0.094). No significant associations were found between AR and age (p = 0.8), race (p = 0.077), or ethnicity (p = 0.2). No AR patients had a documented history of TE. Five of 42 (11.9%) aspirin sensitive patients had TE while taking aspirin, including two females (not on birth control at time of event) and three males.

Conclusions

AR is prevalent in CHD TPVR patients, but TE occurrence did not correlate with AR. However, AR exclusively in females and TE in aspirin sensitive patients, suggests need for further investigations on the most effective TE prophylaxis in this population.
Influence of Hard/Soft Carbon Ratio in Composite Anodes for Enhanced Performance in Sodium‐Ion Battery
Authors: Ahmed Israr , Rosson Lucas , Forsyth Maria , Byrne Nolene
Published: February 2025

Sodium‐ion batteries (SIBs) are an emerging next‐generation technology for sustainable energy storage. In this study, the synthesis and performance of carbon anode materials for SIBs, produced via direct co‐carbonisation of textile waste‐derived hard carbon (HC) and pitch‐derived soft carbon (SC) at various ratios, were investigated. It was found that, as the ratio of HC increased, the rate capacity of the composite carbon anode improved, with the best performing composite anode exhibiting a specific capacity of 334 mAh g−1 at a current density of 50 mA g−1 which exceeded the specific capacity of 100 %HC and 100 %SC. The co carbonisation of the HC with the SC is critical to ensure the stabilisation of the pitch composite with in the new composite anode. A detailed examination of morphology, microstructure and electrochemical properties is reported here.
Kinetic Control and Trapping in the Supramolecular Polymerization of m‐Terphenyl Bis‐Urea Macrocycles
Authors: Wijesekera Gamage Isuri P. , Rushton Isabella G. , Samant Vaibhavi A. , Gbadamosi Fahidat A. , Islam Md Faizul , Smith Mark D. , Wetthasinghe Shehani T. , Garashchuk Sophya , Shimizu Linda S.
Published: February 2025

Herein, we examine pathway complexity in the supramolecular polymerization of a novel m‐terphenyl bis‐urea macrocycle. Designed to induce kinetically metastable states, the macrocycle‘s concentration‐dependent aggregation was studied via 1H NMR and IR spectroscopy in THF and CHCl₃. Temperature‐dependent UV‐Vis spectroscopy in water/THF revealed a cooperative nucleation‐growth mechanism, indicated by a shift in λmax to longer wavelengths upon cooling. Morphological studies using DLS, AFM, and SEM demonstrated fibrous aggregate formation. Thermal hysteresis observed in assembly‐disassembly cycles indicated kinetically trapped species, with cooling governed by kinetic control and heating by thermodynamic processes. Deviations in ΔH values during cooling, compared to van′t Hoff analysis and alignment of heating ΔH values with thermodynamic predictions, reinforced this distinction. Spontaneous nucleation retardation, resulting from monomer trapping, led to lag times of up to 50 minutes under specific conditions. Computational studies revealed the parallel urea conformation as the more stable monomer configuration, whereas the antiparallel conformation is more stable in dimers. By probing pathway complexity of the macrocycle, we demonstrate a distinct ability to control and stabilize kinetically trapped states, broadening the scope for designing macrocyclic supramolecular polymers with tailored properties. This work deepens our understanding of supramolecular dynamics, exploring ON‐pathway mechanisms and advancing tunable supramolecular materials.
Methyl‐π Interactions. Nature of Bonding and Limits of Strength
Authors: Scheiner Steve
Published: February 2025

Both methyl groups and benzene rings are exceedingly common, and they lie near one another in many chemical situations. DFT calculations are used to gauge the strength of the attractive forces between them, and to better understand the phenomena that underlie this attraction. Methane and benzene are taken as the starting point, and substituents of both electron‐withdrawing and donating types are added to each. The interaction energy varies between 1.4 and 5.0 kcal/mol, depending upon the substituents placed on the two groups. The nature of the binding is analyzed via Atoms in Molecules (AIM), Natural Bond Orbital (NBO), Symmetry‐Adapted Perturbation Theory (SAPT), nuclear magnetic resonance (NMR) chemical shifts, and electron density shift diagrams. While there is a sizable electrostatic component, it is dispersion that dominates these interactions, particularly the weaker ones. As such, these interactions cannot be categorized unambiguously as either H‐bonds or tetrel bonds.
Pyrrolation of Melem: A Facile Gateway into the Field of Monomeric s‐Heptazine Chemistry
Authors: Koller Thaddäus J. , Witthaut Kristian , Wolf Florian , Singer Johannes N. , Blahusch Jakob , Li Changyong , Valsamidou Vasiliki , Johrendt Dirk , Schnick Wolfgang
Published: February 2025

Monomeric s‐heptazines are an intriguing class of compounds with many attractive properties for various areas of application such as photocatalysis or organic light‐emitting diodes. However, research into these properties has so far been challenging, as only a few synthetic routes for the preparation of monomeric s‐heptazines are known in the literature. Furthermore, these few reported synthetic pathways generally require the use of specialized equipment that may not be available to all laboratories interested in studying monomeric s‐heptazines. For this reason, a more accessible synthetic route for the preparation of monomeric s‐heptazines has been developed in the course of this work. The central compound of this new approach is 2,5,8‐tri(1H‐pyrrol‐1‐yl)‐s‐heptazine, which could be conveniently synthesized via an acid catalyzed pyrrolation of melem with bench‐stable 2,5‐dimethoxytetrahydrofuran in a simple one‐pot synthesis in air. This compound was shown to be a potent starting material for the synthesis of numerous other monomeric s‐heptazines by reaction with both nucleophiles and electrophiles. The monomeric s‐heptazines thus accessible were analyzed for their crystal structures by single crystal X‐ray diffraction and for their optical properties by ultraviolet/visible and photoluminescence spectroscopy.
Supramolecular polymerization of monomers containing both urea and amide groups: evidence for narcissistic hydrogen bond self‐sorting
Authors: Gallonde William , Shekar Meghana , Dorcet Vincent , Rigaut Stephane , Galangau Olivier
Published: February 2025

In this study, we unambiguously evidence, by mean of UV‐Vis and NMR technics supported by theoretical calculations, that a narcissistic H‐bond self‐sorting takes place during supramolecular polymerization of a newly designed monomer equipped with mixed urea/amide H‐bond donor/acceptor moieties.
A parameter transformation of the anisotropic Matérn covariance function
Authors: Rai Kamal , Brown Patrick E.
Published: February 2025

We describe a polar coordinate transformation of the anisotropy parameters of the Matérn covariance function, which provides two benefits over the standard parameterization. First, it identifies a single point (the origin) with the special case of isotropy. Second, the posterior distribution of the transformed anisotropic angle and ratio is approximately bell‐shaped and unimodal even in the case of isotropy. This has advantages for parameter inference and density estimation. We also apply a transformation to the standard deviation and range such that they are approximately orthogonal. We demonstrate this parameter transformation through two simulated and two real data sets, and conclude by considering possible extensions, such as implementing this transformation for approximate Bayesian inference methods.
Conductive, Copper‐plated, Patinated – Surface Modification on PLA from the 3D Printer
Authors: Zell Lukas , Utz Korbinian , Friedrich Jens
Published: February 2025

In diesem Artikel wird die Oberflächenmodifikation von 3D‐gedruckten Objekten in drei Schritten beschrieben. Zuerst werden Objekte aus Polymilchsäure (PLA) mittels Aceton und Graphit leitfähig gemacht. Anschließend wird auf dieser leitfähigen Schicht Kupfer galvanisch abgeschieden. Im dritten Schritt wird die Kupferschicht einem gezielten Alterungsprozess unterzogen, wobei abhängig der verwendeten Chemikalien eine farbige Kupferpatina entsteht. Dieses Projekt verbindet auf spannende Weise die Themengebiete Kunststoffe, Elektrochemie und kunstvolle Korrosionsprozesse.
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

Background

Childhood 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.

Methods

Untargeted 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.

Results

The 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.

Conclusions

Overall, 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

Background

This study evaluated the safety, pharmacokinetics, and antitumor activity of LY3295668 erbumine as monotherapy and combination therapy in children with relapsed/refractory neuroblastoma.

Methods

Patients 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.

Results

Twenty‐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%.

Conclusions

LY3295668 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

This 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

Blockchain 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

Air 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

Cloud 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

This 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

Enzyme 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

Barley (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

Lignocellulosic 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

This 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

Background

Acquired 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.

Methods

We 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.

Results

Anlotinib‐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.

Conclusion

These 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

Acne 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.
Assessment of Antidiarrheal Effect of Oleuropein Through µ‐Oopioid Receptor Interaction Pathway: In Vivo and in Silico Studies
Authors: Jahan Nishat , Mandal Manoj , Rakib Imam Hossen , Al Hasan Md. Sakib , Mia Emon , Hossain Md. Arif , Yana Noshin Tasnim , Ansari Siddique Akber , Bappi Mehedi Hasan , Wasaf Hasan Ali Mohamod , Sayeed Md Abu , Islam Muhammad Torequl
Published: February 2025

Oleuropein (OLP), a compound predominantly found in olive leaves, has been known for its numerous biological activities, including antioxidant, anti‐inflammatory, and antimicrobial properties. Despite its established therapeutic potential, its role in treating diarrhea has not been extensively explored. This study aimed to evaluate the antidiarrheal effects of OLP in an in vivo model and to investigate its molecular interactions using in silico docking studies, pharmacokinetic predictions, and toxicity analysis. In the in vivo study, castor oil was used to induce diarrhea in 3‐day‐old chicks, and the antidiarrheal effect of OLP was tested at doses of 10 and 20 mg/kg. The standard drug, loperamide (LOP) at 3 mg/kg, was used for comparison. The results showed that OLP at both doses significantly (p < 0.05) reduced diarrheal secretions and increased latency, with the 20 mg/kg dose demonstrating the most effective results. The combination of OLP (20 mg/kg) with LOP (3 mg/kg) further enhanced the antidiarrheal effect. In the in silico study, molecular docking revealed that both OLP and LOP exhibited strong binding affinities (BAs) to the key receptor, μ‐opioid receptor associated with diarrhea, while OLP showed higher BA (‒8.9 kcal/mol) compared to LOP (‒8.7 kcal/mol). Pharmacokinetic analysis of OLP revealed favorable properties and toxicity studies revealed no acute toxicity, with an LD50 of 2000 mg/kg. In conclusion, the findings suggest that OLP possesses significant antidiarrheal potential both in vivo and through receptor interaction, positioning it as a promising natural therapeutic agent for managing diarrhea. Further studies are warranted to fully elucidate its mechanisms of action and clinical applicability.
Liver metastatic recurrence after curative endoscopic submucosal dissection for slightly submucosal invasive gastric cancer: A case report and literature review
Authors: Niikawa Masahiro , Akimoto Teppei , Kirita Kumiko , Yoshida Yuji , Okubo Tomomi , Hayama Korenobu , Hatori Tsutomu , Goto Osamu , Fujimori Shunji , Iwakiri Katsuhiko
Published: February 2025

In Japan, differentiated‐type early gastric cancer with submucosal invasion <500 µm, tumor diameter <3 cm, no lymphovascular invasion, and negative resection margin are included in pathological curative criteria after endoscopic resection (ER). However, there are a few reports presenting local or metastatic recurrence after ER for the lesions described above. A 72‐year‐old man was diagnosed with early gastric cancer and underwent endoscopic submucosal dissection (ESD). Pathological diagnosis was well‐differentiated tubular adenocarcinoma, 8 × 6 mm, T1b1(SM1; 428 µm below the muscularis mucosae), negative lymphovascular invasion, and negative resection margin, which was included in curative criteria. Eighteen months after ESD, the laboratory studies indicated an increase in carcinoembryonic antigen of 17.6 ng/mL (normal range <5 ng/mL). While endoscopy showed no local recurrence finding, contrast‐enhanced computed tomography (CT) showed a metastatic liver tumor in S4. Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid‐enhanced magnetic resonance imaging and 18F‐fluorodeoxyglucose positron emission tomography/CT revealed metastatic liver tumors in S4, S5, and S8. The liver biopsy specimen showed tubular adenocarcinoma and the findings of immunochemical staining were similar to that of the specimen of prior ESD. Thus, he was diagnosed with multiple liver metastatic recurrences after curative ER. Currently, it has been 3 years and 5 months since ESD and 1 year and 11 months since liver metastatic recurrence, and the patient has survived receiving 5th‐line systemic chemotherapy. Here, we report a rare case of liver metastatic recurrence 18 months after curative ESD for early gastric cancer.
Program‐Led and Focused Psychological Interventions
Authors: Wade Tracey D.
Published: February 2025

The use of program‐led and focused psychological interventions in eating disorders, along the spectrum of prevention through to treatment, is growing. Much, however, remains to be understood about how to optimize these interventions and in what contexts and with which populations they are best used. This editorial defines program‐led and focused psychological interventions, gives some examples of these interventions, examines the rationale for these interventions in eating disorders, and identifies fruitful areas of future research. To assist in facilitating further research, the International Journal of Eating Disorders will devote a special issue on this topic.
Using Artificial Intelligence to Advance Eating Disorder Research, Treatment and Practice
Authors: Linardon Jake , Fuller‐Tyszkiewicz Matthew
Published: February 2025

Artificial intelligence (AI) has the potential to revolutionize eating disorder research, treatment, and practice by assisting with complex problems such as predicting illness prognosis, supporting diagnostic decisions, tailoring treatment plans, and even data analysis and study design choices. Yet, research on the applications of AI in eating disorders remains limited. This editorial discusses the importance of AI, explores practical applications, and outlines key directions for future research. To accelerate progress, the International Journal of Eating Disorders will publish a special issue on AI in this context, anticipated in December 2025.
Evidence for the Vacated Niche Hypothesis in Parasites of Invasive Mammals
Authors: Schatz Annakate M. , Park Andrew W.
Published: February 2025

Species redistribution and invasion are becoming increasingly common due to climate change and anthropogenic impacts. Understanding the resultant shifts in host–parasite associations is important for anticipating disruptions to host communities, disease cycles, and conservation efforts. In this paper, we bring together the enemy release and vacated niche hypotheses to relate parasite acquisition and retention, two distinct yet intertwined processes that play out during host invasion. Using the Global Mammal Parasite Database, we test for net enemy release based on differences in parasite species richness, and we develop a novel taxonomic null modeling approach to demonstrate that parasites fill vacated niches. We find evidence of net enemy release, and our taxonomic null models indicate replacement of lost parasites by taxonomically similar acquired ones, over and above what might be expected by chance. Our work suggests that both enemy release and vacated niche hypotheses provide valuable frameworks through which to understand and predict changing host–parasite associations, which may include insights on how climate change and anthropogenic influences perturb and reorganize communities and ecosystems.
Integrating Functional and Phylogenetic Diversity to Assess Bird Community Assembly Along the Major Rivers of Hainan Island, South China
Authors: Lin Sidan , Liang Wei
Published: February 2025

Understanding the mechanisms associated with community assembly can contribute to explaining the formation and maintenance of biodiversity patterns. In this study, we used the line transect method to survey breeding birds along the three major rivers of the Nandu River, Changhua River and Wanquan River on Hainan Island, south China. The patterns of community assembly were subsequently assessed by integrating functional and phylogenetic diversity, whereas environmental factors and interspecific competition intensity were incorporated to determine whether community assembly in these rivers is driven by environmental filtering or interspecific competition. Our findings revealed that bird communities within rivers were characterized by an overall slight clustering (i.e., more similar species), with the upper reaches of the Changhua River and the lower reaches of the Nandu River showing over‐dispersion, whereas the lower, middle, and upper reaches of the Wanquan River all showed clustering. Altitude and the human influence index were identified as the main factors driving bird community assembly within the three major rivers. Notably, for bird communities along different river reaches, the integration of functional and phylogenetic diversity prevented the mis‐classification of over‐dispersion or clustering in community structure caused by traits with weak phylogenetic signals, or the observation of traits unrelated to community assembly patterns. This empirical study demonstrates the importance of integrating functional and phylogenetic diversity, which not only contributes to gaining an understanding of the mechanisms underlying the development of community assemblies but also facilitates a determination of the extents to which function and phylogeny contribute to shaping the patterns of communities.
Predictors of sustained reverse remodelling in patients with heart failure with reduced ejection fraction
Authors: Furquim Silas Ramos , Bocchi Edimar Alcides , Lira Maria Tereza Sampaio de Sousa , Wanderley Mauro Rogerio de Barros , de Marchi Daniel Catto , Maciel Pamela Camara , Zimerman Andre , Ramires Felix Jose Alvarez , Nastari Luciano , Biselli Bruno , Chizzola Paulo Roberto , Munhoz Robinson Tadeu , Fernandes Fábio , Ayub‐Ferreira Silvia Moreira
Published: February 2025

Background

Patients with heart failure with reduced ejection fraction (HFrEF) who achieve reverse remodelling (RR) can experience a new decrease in ejection fraction (EF), and the predictors of sustained RR (SRR) are not completely understood.

Objectives

The study aims to identify predictors of SRR in patients with HFrEF after an increase in EF and evaluate SRR prognosis.

Methods

In this retrospective, observational study, we evaluated a real‐life cohort of patients with HFrEF and ≥2 consecutive echocardiograms, divided according to left ventricular EF (LVEF) trajectory: no RR (NRR: 3/3 LVEF measurements < 40%), non‐SRR (NSRR: second LVEF ≥ 40%, third LVEF < 40%), and SRR (SRR: second and third LVEF ≥ 40%).

Results

We included 3628 of 8072 assessed HF patients in the analysis, with mean age 56.2 (±13.4) years, 64.4% male and 77.7% New York Heart Association (NYHA) I–II. Improved EF was observed for 1342 (37%) patients. Among those who achieved RR, 310 (23%) were NSRR, and 1032 (77%) were SRR. The mean (±SE) survival after the second echocardiogram was 10.6 (±0.2) years. The SRR group had the longest survival (12.2 ± 0.3 years), followed by the NSRR (10.6 ± 0.5) and NRR (9.8 ± 0.2 years) groups (P < 0.001). According to logistic multivariable regression, second LVEF [odds ratio (OR) = 1.06, confidence interval (CI) = 1.03–1.90, P < 0.001], second left ventricular end‐systolic diameter (LVESD) (OR = 0.93, CI = 0.90–0.96, P < 0.001), second IV septum thickness (OR = 1.12, CI = 1.03–1.23, P = 0.012), systolic blood pressure (OR = 1.01, CI = 1.00–1.02, P = 0.014), NYHA I–II (OR = 1.86, CI = 1.27–2.74, P = 0.001) and furosemide non‐use (OR = 1.87, CI = 1.27–2.74, P < 0.001) independently predicted SRR.

Conclusions

Patients with greater EF increases and LVESD reductions at EF recovery, greater septum thickness, higher blood pressure, no need for diuretics and NYHA I/II maintenance had the best chance of maintaining recovered ventricular function.