bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initiation Patterns of Disease-Modifying Therapies for Multiple Sclerosis Among US Adults and Children, 2001 Through 2020
Authors: Henderson Mackenzie , Horton Daniel B. , Bhise Vikram , Pal Gian , Bushnell Greta , Dave Chintan V. 
Published: July 2023

ImportanceMany disease-modifying therapies (DMTs) have been approved for multiple sclerosis (MS) in the past 2 decades. Research evaluating how these approvals have changed real-world prescribing patterns is scarce.ObjectiveTo evaluate patterns in DMT initiations between 2001 and 2020 among commercially insured US adults and children with MS.Design, Setting, and ParticipantsThis serial cross-sectional study was conducted from 2001 through 2020 (mean patient enrollment duration, 4.8 years) and used US commercial claims data (MarketScan). Analysis took place between January 2022 and March 2023. Of 287 084 patients with MS identified, 113 583 patients (113 095 adults and 488 children) with MS newly initiated at least 1 DMT.ExposureNew initiation episode of a DMT, defined as no claim for the same DMT in the previous year.Main Outcome MeasureThe proportion of total DMT initiations per year attributable to each DMT. Trends in initiations were evaluated annually.ResultsThe study team identified 153 846 DMT initiation episodes among adults (median age, 46 [IQR, 38-53) years]; 86 133 female [76.2%]) and 583 among children (median age, 16 (IQR, 14-17) years; 346 female [70.9%]). Among adults, use of platform injectables showed an absolute decline of 73.8% over the study period, driven by a 61.2% reduction in interferon β initiations (P &amp;lt; .001 for trend). In contrast, the 2010 introduction of oral DMTs led to a rise in their use from 1.1% (2010) to 62.3% (2020) of all DMT initiations (P = .002 for trend). Infusion therapy initiations remained relatively low, accounting for 3.2% of all initiations since their introduction in 2004 but increased modestly annually after ocrelizumab was introduced (2017), reaching 8.2% of all initiations in 2020 (P &amp;lt; .001 for trend). Children showed similar initiation patterns, except for preferred oral therapy. Between 2019 and 2020, dimethyl fumarate was the most commonly initiated DMT in adults (23.3% to 27.2% of all initiations), while in children fingolimod was the most commonly initiated (34.8% to 68.8%).Conclusions and RelevanceCurrent MS treatment guidelines emphasize shared decision-making between patients and clinicians to balance treatment efficacy, safety, cost, and convenience. This study found that oral DMTs were the predominant DMT type initiated by 2020. The cause of this shift cannot be determined from this study, but may reflect several factors, including convenience of administration, direct-to-consumer advertising, or insurance restrictions.
Cooperative distributed extremum seeking control for coupled multiagent systems based on distributed identification‐gradient tracking
Authors: Ma Wenrui , Xu Zuhua , Zhao Jun , Zhang ShuangXi , Shao Zhijiang 
Published: July 2023

SummaryThis paper proposes a cooperative distributed extremum seeking control (ESC) approach for solving distributed optimization problems in static and dynamical multiagent systems, where the agents' coupled dynamics are unknown and only local cost values can be measured. The approach begins with each agent estimating the local gradient information of the unknown local cost function through recursive identification using measured local cost values. Subsequently, the distributed identification‐gradient tracking (DIGT) algorithm is employed to enable each agent to track the global gradient information of the global cost function, utilizing the estimated local gradient information from itself and its neighbors in the network. The proposed cooperative distributed ESC method enables the multiagent system to reach the extreme point of the global cost function under model‐free scenarios. Furthermore, the convergence properties of the approach are established for both static and dynamical multiagent systems. Finally, numerical examples are presented to demonstrate the effectiveness and stability of the proposed approach.
Regulation of Osteoblast to Osteocyte Differentiation by Cyclin‐Dependent Kinase‐1
Authors: Tanaka Tomoyuki , Miyakoshi Yuri , Kobayashi Yutaka , Xiaolong Sun , Daiyang Yu , Ochi Hiroki , Sato Shingo , Kato Tsuyoshi , Yoshii Toshitaka , Okawa Atsushi , Kaldis Philipp , Inose Hiroyuki 
Published: July 2023

AbstractOsteocytes have recently been identified as a new regulator of bone remodeling, but the detailed mechanism of their differentiation from osteoblasts remains unclear. The purpose of this study is to identify cell cycle regulators involved in the differentiation of osteoblasts into osteocytes and determine their physiological significance. The study uses IDG‐SW3 cells as a model for the differentiation from osteoblasts to osteocytes. Among the major cyclin‐dependent kinases (Cdks), Cdk1 is most abundantly expressed in IDG‐SW3 cells, and its expression is down‐regulated during differentiation into osteocytes. Inhibition of CDK1 activity reduces IDG‐SW3 cell proliferation and differentiation into osteocytes. Osteocyte and Osteoblast‐specific Cdk1 knockout in mice (Dmp1‐Cdk1KO) results in trabecular bone loss. Pthlh expression increases during differentiation, but inhibiting CDK1 activity reduces Pthlh expression. Parathyroid hormone‐related protein concentration is reduced in the bone marrow of Dmp1‐Cdk1KO mice. Four weeks of Parathyroid hormone administration partially recovers the trabecular bone loss in Dmp1‐Cdk1KO mice. These results demonstrate that Cdk1 plays an essential role in the differentiation from osteoblast to osteocyte and the acquisition and maintenance of bone mass. The findings contribute to a better understanding of the mechanisms of bone mass regulation and can help develop efficient therapeutic strategies for osteoporosis treatment.
A Transdermal Drug Delivery System Based on Nucleic Acid Nanomaterials for Skin Photodamage Treatment
Authors: Xie Yu , He Jiajun , Li Songhang , Chen Xingyu , Zhang Tianxu , Zhao Yuxuan , Lin Yunfeng , Cai Xiaoxiao 
Published: July 2023

AbstractSkin photodamage, which is induced by ultraviolet (UV) radiation, is a prevalent cause of skin damage. In this study, a transdermal drug delivery system is developed for the topical treatment of skin photodamage, which is composed of tetrahedral framework nucleic acids (tFNAs) and lipoic acid (LA). The tFNAs‐LA (TLA) nanocomposite exhibits excellent biocompatibility, as well as antioxidant, anti‐apoptotic, and anti‐inflammatory capabilities. tFNA, as a carrier, facilitates TLA for cell entry and skin penetration, while the loaded LA enhances the antioxidant and anti‐inflammatory capabilities. In photodamaged human dermal fibroblast (HDF), TLA promotes proliferation and migration while inhibiting apoptosis activation and reactive oxygen species production. Moreover, TLA modulates apoptosis‐related proteins and NF‐κB signaling pathways, increasing cellular secretion while suppressing inflammatory responses in photodamaged HDF cells. In the in vivo experiment, topical application of TLA promotes tissue healing in photodamaged skin, and regulates the expression of inflammation and collagen‐related proteins. It is suggested that the transdermal ability of TLA enables non‐invasive therapy for skin photodamage, highlighting the potential of employing nucleic acid‐based transdermal drug delivery systems for skin disease.
An Improved Simulated Annealing Algorithm in Dataset Domain for Optimizing Robust Workpiece Fixture Layout
Authors: Ding Heng , Dong Yude , Gao Haoyu , Cheng Hui , Yang Zhongshu , Liang Yulei 
Published: July 2023

AbstractThe robust layout of the fixture on the workpiece solves the problem of workpiece fixing well. Aiming at the problem of workpiece position error caused by fixture source error on workpiece surface, an improved simulated annealing algorithm based on dataset domain is adopted to reduce the workpiece position error caused by fixture locator deviation as much as possible. To find a better robust layout way, a point differentiation method is proposed to discretize continuous workpieces to obtain the dataset domain. Meanwhile, two objective functions considering curvature and non‐curvature are used to evaluate the placement scheme of locators. A point differentiation method is proposed to discretize continuous workpieces to obtain the dataset domains. Meanwhile, two objective functions considering curvature and non‐curvature are used to evaluate locator layout schemes. To improve the performance of the algorithm, an AHP‐based multi‐attribute decision‐making method is used to find a set of optimal parameters to configure the algorithm. The benchmark example and practical verification show that the locator obtained by the algorithm proposed is less discrete and denser, which solves the problem of fixture positioning very well, and the position error of the workpiece is effectively reduced.
A PDA‐Functionalized 3D Lung Scaffold Bioplatform to Construct Complicated Breast Tumor Microenvironment for Anticancer Drug Screening and Immunotherapy
Authors: Zhang Wanheng , Chen Yan , Li Mengyuan , Cao Shucheng , Wang Nana , Zhang Yingjian , Wang Yongtao 
Published: July 2023

Abstract2D cell culture occupies an important place in cancer progression and drug discovery research. However, it limitedly models the “true biology” of tumors in vivo. 3D tumor culture systems can better mimic tumor characteristics for anticancer drug discovery but still maintain great challenges. Herein, polydopamine (PDA)‐modified decellularized lung scaffolds are designed and can serve as a functional biosystem to study tumor progression and anticancer drug screening, as well as mimic the tumor microenvironment. PDA‐modified scaffolds with strong hydrophilicity and excellent cell compatibility can promote cell growth and proliferation. After 96 h treatment with 5‐FU, cisplatin, and DOX, higher survival rates in PDA‐modified scaffolds are observed compared to nonmodified scaffolds and 2D systems. The E‐cadhesion formation, HIF‐1α‐mediated senescence decrease, and tumor stemness enhancement can drive drug resistance and antitumor drug screening of breast cancer cells. Moreover, there is a higher survival rate of CD45+/CD3+/CD4+/CD8+ T cells in PDA‐modified scaffolds for potential cancer immunotherapy drug screening. This PDA‐modified tumor bioplatform will supply some promising information for studying tumor progression, overcoming tumor resistance, and screening tumor immunotherapy drugs.
Vertical Phase Regulation with 1,3,5‐Tribromobenzene Leads to 18.5% Efficiency Binary Organic Solar Cells
Authors: Zhu Chaofeng , Chung Sein , Zhao Jingjing , Sun Yuqing , Zhao Bin , Zhao Zhenmin , Kim Seunghyun , Cho Kilwon , Kan Zhipeng 
Published: July 2023

AbstractThe sequential deposition method assists the vertical phase distribution in the photoactive layer of organic solar cells, enhancing power conversion efficiencies. With this film coating approach, the morphology of both layers can be fine‐tuned with high boiling solvent additives, as frequently applied in one‐step casting films. However, introducing liquid additives can compromise the morphological stability of the devices due to the solvent residuals. Herein, 1,3,5‐tribromobenzene (TBB) with high volatility and low cost, is used as a solid additive in the acceptor solution and combined thermal annealing to regulate the vertical phase in organic solar cells composed of D18‐Cl/L8‐BO. Compared to the control cells, the devices treated with TBB and those that underwent additional thermal processing exhibit increased exciton generation rate, charge carrier mobility, charge carrier lifetime, and reduced bimolecular charge recombination. As a result, the TBB‐treated organic solar cells achieve a champion power conversion efficiency of 18.5% (18.1% averaged), one of the highest efficiencies in binary organic solar cells with open circuit voltage exceeding 900 mV. This study ascribes the advanced device performance to the gradient‐distributed donor‐acceptor concentrations in the vertical direction. The findings provide guidelines for optimizing the morphology of the sequentially deposited top layer to achieve high‐performance organic solar cells.
Methods for Characterizing Intercalation in Aqueous Zinc Ion Battery Cathodes: A Review
Authors: Tay Ian Rongde , Xue Junmin , Lee Wee Siang Vincent 
Published: July 2023

AbstractAqueous zinc ion batteries have gained research attention as a safer, economical and more environmentally friendly alternative to lithium‐ion batteries. Similar to lithium batteries, intercalation processes play an important role in the charge storage behaviour of aqueous zinc ion batteries, with the pre‐intercalation of guest species in the cathode being also employed as a strategy to improve battery performance. In view of this, proving hypothesized mechanisms of intercalation, as well as rigorously characterizing intercalation processes in aqueous zinc ion batteries is crucial to achieve advances in battery performance. This review aims to evaluate the range of techniques commonly used to characterize intercalation in aqueous zinc ion battery cathodes, providing a perspective on the approaches that can be utilized to rigorously understand such intercalation processes.
3D Printing of Microenvironment‐Specific Bioinspired and Exosome‐Reinforced Hydrogel Scaffolds for Efficient Cartilage and Subchondral Bone Regeneration
Authors: Li Qi , Yu Huilei , Zhao Fengyuan , Cao Chenxi , Wu Tong , Fan Yifei , Ao Yingfang , Hu Xiaoqing 
Published: July 2023

AbstractIn clinical practice, repairing osteochondral defects presents a challenge due to the varying biological properties of articular cartilages and subchondral bones. Thus, elucidating how spatial microenvironment‐specific biomimetic scaffolds can be used to simultaneously regenerate osteochondral tissue is an important research topic. Herein, a novel bioinspired double‐network hydrogel scaffold produced via 3D printing with tissue‐specific decellularized extracellular matrix (dECM) and human adipose mesenchymal stem cell (MSC)‐derived exosomes is described. The bionic hydrogel scaffolds promote rat bone marrow MSC attachment, spread, migration, proliferation, and chondrogenic and osteogenic differentiation in vitro, as determined based on the sustained release of bioactive exosomes. Furthermore, the 3D‐printed microenvironment‐specific heterogeneous bilayer scaffolds efficiently accelerate the simultaneous regeneration of cartilage and subchondral bone tissues in a rat preclinical model. In conclusion, 3D dECM‐based microenvironment‐specific biomimetics encapsulated with bioactive exosomes can serve as a novel cell‐free recipe for stem cell therapy when treating injured or degenerative joints. This strategy provides a promising platform for complex zonal tissue regeneration whilst holding attractive clinical translation potential.
Probing the Competition between Duplex, G‐Quadruplex and i‐Motif Structures of the Oncogenic c‐Myc DNA Promoter Region
Authors: Pandey Akanksha , Roy Sarupa , Srivatsan Seergazhi G. 
Published: July 2023

AbstractDevelopment of probe systems that provide unique spectral signatures for duplex, G‐quadruplex (GQ) and i‐motif (iM) structures is very important to understand the relative propensity of a G‐rich‐C‐rich promoter region to form these structures. Here, we devise a platform using a combination of two environment‐sensitive nucleoside analogs namely, 5‐fluorobenzofuran‐modified 2′‐deoxyuridine (FBF‐dU) and 5‐fluoro‐2′‐deoxyuridine (F‐dU) to study the structures adopted by a promoter region of the c‐Myc oncogene. FBF‐dU serves as a dual‐purpose probe containing a fluorescent and 19F NMR label. When incorporated into the C‐rich sequence, it reports the formation of different iMs via changes in its fluorescence properties and 19F signal. F‐dU incorporated into the G‐rich ON reports the formation of a GQ structure whose 19F signal is clearly different from the signals obtained for iMs. Rewardingly, the labeled ONs when mixed with respective complementary strands allows us to determine the relative population of different structures formed by the c‐Myc promoter by the virtue of the probe's ability to produce distinct and resolved 19F signatures for different structures. Our results indicate that at physiological pH and temperature the c‐Myc promoter forms duplex, random coil and GQ structures, and does not form an iM. Whereas at acidic pH, the mixture largely forms iM and GQ structures. Taken together, our system will complement existing tools and provide unprecedented insights on the population equilibrium and dynamics of nucleic acid structures under different conditions.
Structure Evolution of V2O5 as Electrode Materials for Metal‐Ion Batteries
Authors: Niu Xiaogang , Li Nan , Chen Yifan , Zhang Jianwen , Yang Yusi , Tan Lulu , Wu Jianghao , Guo Lin , Zhu Yujie 
Published: July 2023

AbstractWith the increasing demand for next‐generation electrochemical energy storage systems, various kinds of metal‐ion batteries have been developed in the past several decades, such as lithium‐ion batteries (LIBs), sodium‐ion batteries (NIBs), potassium‐ion batteries (KIBs), magnesium‐ion batteries (MIBs), zinc‐ion batteries (ZIBs), calcium‐ion batteries (CIBs), and aluminum‐ion batteries (AIBs). Due to its open structure, large interlayer spacings, multiple valence states, and reversible structural variations, layered V2O5, including two polymorphs of single layered α‐V2O5 and double layered V2O5 ⋅ nH2O, has been reported as a universal electrode material for all kinds of metal‐ion batteries mentioned above. In this review, we aim to summarize and compare the structure evolution of α‐V2O5 and V2O5 ⋅ nH2O during the insertion/extraction of various kinds of metal‐ions. This short review is expected to be helpful to comprehensively understand the structure evolution mechanism of α‐V2O5 and V2O5 ⋅ nH2O reacting with different metallic charge carriers and inspire the development of new electrode materials for high‐performance metal‐ion batteries.
Functional magnetic resonance imaging study of children's brain development in phonological processing and speeded naming
Authors: Song Zeyu , Jiang Zhenqi , Fan Yingwei , Lu Liang , Zhang Zhao , Wang Yifei , Chen Yu , Liu Lifei , Tang Xiaoying , Li Hanjun 
Published: July 2023

AbstractThe brain structure and language skills of children are understood to be in a phase of rapid development and are especially represented by key phonological‐semantic expressions that actively develop with age. In the present study, resting‐state functional magnetic resonance imaging data from 85 healthy children were retrospectively analyzed. Correlations of the phonological processing and speeded naming of specific brain regions of interest with age were assessed using the fractional amplitude of low‐frequency fluctuations (fALFF), degree centrality (DC), regional homogeneity (ReHo), and chain mediation effect analysis. Our results suggest that the developmental stages of children's posterior cingulate gyrus (PCC) and right inferior frontal gyrus (IFG) mediate language development in children. Additionally, the functional similarity of the bilateral IFG triangular part was noted during development as was the stronger activation and higher local and whole‐brain connectivity of the left IFG triangular part. Moreover, the PCC displayed stronger activation and higher local connectivity in the same period. Our data suggest that the development of the PCC and right IFG and the similarity of bilateral IFG function are important imaging markers of phonological processing and speeded naming in children and that the PCC and IFG show a more comprehensive development with age.
Semicarbazides Carrying Indole Core: Synthesis, Cytotoxicity Evaluation against Human Breast Cancer Cell Lines, and Molecular Modeling Studies
Authors: Çelik Beyza , Buran Uğur Sümeyye , Baran Münevver , Gündüz Miyase Gözde , Keskin Selbi , Önder Gözde Özge , Bitgen Nazmiye , Kaya Serdal , Doğan Şengül Dilem 
Published: July 2023

AbstractIn this article, we report the synthesis and cytotoxicity evaluation of novel indole‐carrying semicarbazide derivatives (IS1‐IS15). The target molecules were obtained by the reaction of aryl/alkyl isocyanates with 1H‐indole‐2‐carbohydrazide that was in‐house synthesized from 1H‐indole‐2‐carboxylic acid. Following structural characterization by 1H‐NMR, 13C‐NMR, and HR‐MS, IS1‐IS15 were investigated for their cytotoxic activity against human breast cancer cell lines, MCF‐7 and MDA‐MB‐231. According to the data obtained from the MTT assay, phenyl ring with a lipophilic group at its para‐position and alkyl moiety were preferential substituents on the indole‐semicarbazide scaffold for antiproliferative activity. The effect of IS12 (N‐(4‐chloro‐3‐(trifluoromethyl)phenyl)‐2‐(1H‐indole‐2‐carbonyl)hydrazine‐1‐carboxamide), the compound that demonstrated remarkable antiproliferative activity on both cell lines, was also evaluated on the apoptotic pathway. Moreover, the calculation of critical descriptors constituting drug‐likeness confirmed the position of the selected compounds in the anticancer drug development process. Finally, molecular docking studies suggested the inhibition of tubulin polymerization as the potential activity mechanism of this class of molecules.
Bioactive Thiosemicarbazone Coordination Metal Complexes: Synthesis, Characterization, Theoretical analysis, Biological Activity, Molecular Docking and ADME analysis**
Authors: Jain Pallavi , Vishvakarma Vijay K. , Singh Prashant , Yadav Sandeep , Kumar Rajesh , Chandra Sulekh , Kumar Dinesh , Misra Namita 
Published: July 2023

AbstractMn(II) and Cu(II) complexes having the formula [M(L)2]X2 of ligand, i. e., 2‐acetyl‐5‐methylfuranthiosemicarbazone were synthesized. Various analytical and spectroscopic techniques described the structure of synthesized complexes. Molar conductance confirmed the electrolytic nature of the complexes. The theoretical study of the complexes explained the structural property and reactivity. The chemical reactivity, interaction and stability of the ligand and metal complexes were studied with the help of global reactivity descriptors. MEP analysis was used to investigate the charge transfer in the ligand. The biological potency was evaluated against two bacteria and two fungi. Complexes demonstrated superior inhibitory action to ligand. The inhibitory effect was also checked at the atomic scale using molecular docking, which confirmed the experimental results. Cu(II) complex was shown to have the most inhibitory effect in experimental and theoretical studies. To check the bioavailability and drug‐likeness, ADME analysis was also done.
Revisiting sp2 Dilithio Methandiides: From Geometric Curiosity to Simple Bonding Description
Authors: Leach Isaac F. , Speelman Tom , Somsen Chiel , Klein Johannes E. M. N. , Havenith Remco W. A. 
Published: July 2023

AbstractThe reported tetracoordinate dilithio methandiide complex from Liddle and co‐workers (1) is investigated from a coordination chemistry perspective, to probe the origin of its intriguing geometry. Through the application of a variety of computational techniques, non‐covalent (steric, electrostatic) interactions are found to be dominant. Further, we arrive at a bonding description which emphasizes the tricoordinate sp2‐hybridized nature of the central methandiide carbon, differing somewhat from the original proposal. Thus, 1 is distinct from other dilithio methandiides since it contains only one C−Li σ‐bond, and is found to be comparable to a simple aryllithium compound, phenyllithium.