bluuebunny/crossref_metadata_2025_split huggingface dataset:
Penalized maximum likelihood inference under the mixture cure model in sparse data
Authors: Xu Changchang , Bull Shelley B. 
Published: March 2023

IntroductionWhen a study sample includes a large proportion of long‐term survivors, mixture cure (MC) models that separately assess biomarker associations with long‐term recurrence‐free survival and time to disease recurrence are preferred to proportional‐hazards models. However, in samples with few recurrences, standard maximum likelihood can be biased.Objective and MethodsWe extend Firth‐type penalized likelihood (FT‐PL) developed for bias reduction in the exponential family to the Weibull‐logistic MC, using the Jeffreys invariant prior. Via simulation studies based on a motivating cohort study, we compare parameter estimates of the FT‐PL method to those by ML, as well as type 1 error (T1E) and power obtained using likelihood ratio statistics.ResultsIn samples with relatively few events, the Firth‐type penalized likelihood estimates (FT‐PLEs) have mean bias closer to zero and smaller mean squared error than maximum likelihood estimates (MLEs), and can be obtained in samples where the MLEs are infinite. Under similar T1E rates, FT‐PL consistently exhibits higher statistical power than ML in samples with few events. In addition, we compare FT‐PL estimation with two other penalization methods (a log‐F prior method and a modified Firth‐type method) based on the same simulations.DiscussionConsistent with findings for logistic and Cox regressions, FT‐PL under MC regression yields finite estimates under stringent conditions, and better bias‐and‐variance balance than the other two penalizations. The practicality and strength of FT‐PL for MC analysis is illustrated in a cohort study of breast cancer prognosis with long‐term follow‐up for recurrence‐free survival.
Physicochemical Properties and Route of Systemic Delivery Control the In Vivo Dynamics and Breakdown of Radiolabeled Gold Nanostars
Authors: Wen Xiaona , Ou Luping , Cutshaw Gabriel , Uthaman Saji , Ou Yu‐Chuan , Zhu Tian , Szakas Sarah , Carney Brandon , Houghton Jacob , Gundlach‐Graham Alexander , Rafat Marjan , Yang Kai , Bardhan Rizia 
Published: March 2023

AbstractThe in vivo dynamics of nanoparticles requires a mechanistic understanding of multiple factors. Here, for the first time, the surprising breakdown of functionalized gold nanostars (F‐AuNSs) conjugated with antibodies and 64Cu radiolabels in vivo and in artificial lysosomal fluid ex vivo, is shown. The short‐term biodistribution of F‐AuNSs is driven by the route of systemic delivery (intravenous vs intraperitoneal) and long‐term fate is controlled by the tissue type in vivo. In vitro studies including endocytosis pathways, intracellular trafficking, and opsonization, are combined with in vivo studies integrating a milieu of spectroscopy and microcopy techniques that show F‐AuNSs dynamics is driven by their physicochemical properties and route of delivery. F‐AuNSs break down into sub‐20 nm broken nanoparticles as early as 7 days postinjection. Martini coarse‐grained simulations are performed to support the in vivo findings. Simulations suggest that shape, size, and charge of the broken nanoparticles, and composition of the lipid membrane depicting various tissues govern the interaction of the nanoparticles with the membrane, and the rate of translocation across the membrane to ultimately enable tissue clearance. The fundamental study addresses critical gaps in the knowledge regarding the fate of nanoparticles in vivo that remain a bottleneck in their clinical translation.
Glycol‐Split Heparin‐Linked Prodrug Nanoparticles Target the Mitochondrion Apparatus for Cancer Metastasis Treatment
Authors: Sun Feng , Hou Huiwen , Li Yan , Tang Wen , Wang Jie , Lu Lu , Fu Jiaai , Liu Zengmei , Gao Didi , Zhao Feiyan , Gao Xinqing , Ling Peixue , Wang Fengshan , Tan Haining 
Published: March 2023

AbstractThe progression and metastasis of solid tumors rely strongly on neovascularization. However, angiogenesis inhibitors alone cannot meet the needs of tumor therapy. This study prepared a new drug conjugate (PTX‐GSHP‐CYS‐ES2, PGCE) by combining polysaccharides (heparin without anticoagulant activity, GSHP), chemotherapeutic drugs (paclitaxel, PTX), and antiangiogenic drugs (ES2). Furthermore, a tumor‐targeted prodrug nanoparticle delivery system is established. The nanoparticles appear to accumulate in the mitochondrial of tumor cells and achieve ES2 and PTX release under high glutathione and acidic environment. It has been confirmed that PGCE inhibited the expression of multiple metastasis‐related proteins by targeting the tumor cell mitochondrial apparatus and disrupting their structure. Furthermore, PGCE nanoparticles inhibit migration, invasion, and angiogenesis in B16F10 tumor‐bearing mice and suppress tumor growth and metastasis in vitro. Further in vitro and in vivo experiments show that PGCE has strong antitumor growth and metastatic effects and exhibits efficient anti‐angiogenesis properties. This multi‐targeted nanoparticle system potentially enhances the antitumor and anti‐metastatic effects of combination chemotherapy and antiangiogenic drugs.
Specific Chemiluminescence Imaging and Enhanced Photodynamic Therapy of Bacterial Infections by Hemin‐Modified Carbon Dots
Authors: Cheng Ke , Wang Henggang , Sun Shan , Wu Mingyu , Shen Hongzhe , Chen Ke , Zhang Zhiyuan , Li Si , Lin Hengwei 
Published: March 2023

AbstractAntibacterial photodynamic therapy (aPDT) is a promising antibiotics‐alternative strategy for bacterial infectious diseases, which features broad‐spectrum antibacterial activity with a low risk of inducing bacterial resistance. However, clinical applications of aPDT are still hindered by the hydrophobicity‐caused inadequate photodynamic activity of conventional photosensitizers and the hypoxic microenvironment of bacterial infections. To address these problems, herein, a promising strategy is developed to achieve specific chemiluminescence (CL) imaging and enhanced PDT of bacterial infections using hemin‐modified carbon dots (H‐CDs). The H‐CDs can be facilely prepared and exhibit favorable water solubility, augmented photodynamic activity, and unique peroxidase‐mimicking capacity. Compared with the free CDs, the photodynamic efficacy of H‐CDs is significantly augmented due to the increased electron–hole separation efficiency. Moreover, the peroxidase catalytic performance of H‐CDs enables not only infection identification via bacterial infection microenvironment‐responsive CL imaging but also oxygen self‐supplied aPDT with hypoxia‐relief‐enhanced bacteria inactivation effects. Finally, the enhanced aPDT efficiencies of H‐CDs are validated in both in vivo abscess and infected wound models. This work may provide an effective antibacterial platform for the selective imaging‐guided treatment of bacterial infections.
Decreasing Interfacial Pitfalls with Self‐Grown Sheet‐Like Li2S Artificial Solid‐Electrolyte Interphase for Enhanced Cycling Performance of Lithium Metal Anode
Authors: Zhang Rui , Chen Biao , Shi Chunsheng , Sha Junwei , Ma Liying , Liu Enzuo , Zhao Naiqin 
Published: March 2023

AbstractConstructing a 3D composite Li metal anode (LMA) along with the engineering of artificial solid electrolyte interphase (SEI) is a promising strategy for achieving dendrite‐free Li deposition and high cycling stability. The nanostructure of artificial SEI is closely related to the performance of the LMA. Herein, the self‐grown process and morphology of in situ formed Li2S during lithiation of CuxS is studied systematically, and a large‐sized sheet‐like Li2S layer as an artificial SEI is in situ generated on the inner surface of a 3D continuous porous Cu skeleton (3DCu@Li2S‐S). The sheet‐like Li2S layer with few interfacial pitfalls (Cu/Li2S heterogeneous interface) possesses enhanced diffusion of Li ions. And the continuous porous structure provides transport channels for lithium‐ion transport. As a result, the 3DCu@Li2S‐S presents a high Coulombic efficiency (99.3%), long cycle life (500 cycles), and high‐rate performance (10 mA cm−2). Furthermore, Li/3DCu@Li2S anode fabricated by thermal infusion method inherits the synergistic advantages of sheet‐like Li2S and continuous porous structure. The Li/3DCu@Li2S anode shows significantly enhanced cycling life in both liquid and solid electrolytes. This work provides a new concept to design artificial SEI for LMA with high safe and high performance.
Regulating π‐Conjugation in sp2‐Carbon‐Linked Covalent Organic Frameworks for Efficient Metal‐Free CO2 Photoreduction with H2O
Authors: Yang Lan , Yan Wenkai , Yang Na , Wang Guofeng , Bi Yingpu , Tian Chengcheng , Liu Honglai , Zhu Xiang 
Published: March 2023

AbstractThe development of sp2‐carbon‐linked covalent organic frameworks (sp2c‐COFs) as artificial photocatalysts for solar‐driven conversion of CO2 into chemical feedstock has captured growing attention, but catalytic performance has been significantly limited by their intrinsic organic linkages. Here, a simple, yet efficient approach is reported to improve the CO2 photoreduction on metal‐free sp2c‐COFs by rationally regulating their intrinsic π‐conjugation. The incorporation of ethynyl groups into conjugated skeletons affords a significant improvement in π‐conjugation and facilitates the photogenerated charge separation and transfer, thereby boosting the CO2 photoreduction in a solid‐gas mode with only water vapor and CO2. The resultant CO production rate reaches as high as 382.0 µmol g−1 h−1, ranking at the top among all additive‐free CO2 photoreduction catalysts. The simple modulation approach not only enables to achieve enhanced CO2 reduction performance but also simultaneously gives a rise to extend the understanding of structure‐property relationship and offer new possibilities for the development of new π‐conjugated COF‐based artificial photocatalysts.
A Mesoporous Tungsten Oxynitride Nanofibers/Graphite Felt Composite Electrode with High Catalytic Activity for the Cathode in Zn‐Br Flow Battery
Authors: Jung HyunJin , Lee JaeHyuk , Park JaeYun , Shin Kyungjae , Kim Hee‐Tak , Cho EunAe 
Published: March 2023

AbstractHigh electrochemical polarization during a redox reaction in the electrode of aqueous zinc–bromine flow batteries largely limits its practical implementation as an effective energy storage system. This study demonstrates a rationally‐designed composite electrode that exhibits a lower electrochemical polarization by providing a higher number of catalytically‐active sites for faster bromine reaction, compared to a conventional graphite felt cathode. The composite electrode is composed of electrically‐conductive graphite felt (GF) and highly active mesoporous tungsten oxynitride nanofibers (mWONNFs) that are prepared by electrospinning and simple heat treatments. Addition of the 1D mWONNFs to porous GF produces a web‐like structure that significantly facilitates the reaction kinetics and ion diffusion. The cell performance achieves in this study demonstrated high energy efficiencies of 89% and 80% at current densities of 20 and 80 mA cm−2, respectively. Furthermore, the cell can also be operated at a very high current density of 160 mA cm−2, demonstrating an energy efficiency of 62%. These results demonstrate the effectiveness of the mWONNF/GF composite as the electrode material in zinc–bromine flow batteries.
Effect of Functional Group Modifications on the Photocatalytic Performance of g‐C3N4
Authors: Wang Na , Cheng Lei , Liao Yulong , Xiang Quanjun 
Published: March 2023

AbstractIn recent years, photocatalysis has received increasing attention in alleviating energy scarcity and environmental treatment, and graphite carbon nitride (g‐C3N4) is used as an ideal photocatalyst. However, it still remains numerous challenges to obtain the desirable photocatalytic performance of intrinsic g‐C3N4. Functional group functionalization, formed by introducing functional groups into the bulk structure, is one of the common modification techniques to modulate the carrier dynamics and increases the number of active sites, offering new opportunities to break the limits for structure‐to‐performance relationship of g‐C3N4. Nevertheless, the general overview of the advance of functional group modification of g‐C3N4 is less reported yet. In order to better understand the structure‐to‐performance relationship at the molecular level, a review of the latest development of functional group modification is urgently needed. In this review, the functional group modification of g‐C3N4 in terms of structures, properties, and photocatalytic activity is mainly focused, as well as their mechanism of reaction from the molecular level insights is explained. Second, the recent progress of the application of introducing functional groups in g‐C3N4 is introduced and examples are given. Finally, the difficulties and challenges are presented, and based on this, an outlook on the future research development direction is shown.
A Cascade‐Targeted Enzyme‐Instructed Peptide Self‐Assembly Strategy for Cancer Immunotherapy through Boosting Immunogenic Cell Death
Authors: Xie Limin , Ding Yinghao , Zhang Xiangyang , Zhang Zhenghao , Zeng Sheng , Wang Ling , Yang Zhimou , Liu Qian , Hu Zhi‐Wen 
Published: March 2023

AbstractImmunogenic cell death (ICD) approaches by encumbering mitochondrial functions provide great promise for the treatment of malignant tumors, but these kinds of ICD strategies are still in their infancy. Here, one multifunctional drug‐loaded, cascade‐targeted, and enzyme‐instructed self‐assembling peptide nanomedicine (Comp. 4) for ICD‐based cancer therapy is constructed. Comp. 4 consists of 1) lonidamine (LND) that specifically interferes with mitochondrial functions; 2) a programmed death ligand 1 (PD‐L1) binding peptide sequence (NTYYEDQG) and a mitochondria‐specific motif (triphenylphosphonium, TPP) that can sequentially control the cell membrane and mitochondria targeting capacities, respectively; and 3) a ‐GDFDFpDY‐ assembly core to in situ organize peptide assemblies responsive to alkaline phosphatase (ALP). Comp. 4 demonstrates noticeable structural and morphological transformations in the presence of ALP and produces peptide assemblies in mouse colon cancer cells (CT26) with high expressions of both ALP and PD‐L1. Moreover, the presence of PD‐L1‐ and mitochondria‐specific motifs can assist Comp. 4 for effective endocytosis and endosomal escape, forming peptide assemblies and delivering LND into mitochondria. Consequently, Comp. 4 shows superior capacities to in vivo induce abundant mitochondrial oxidative stress, provoke robust ICD responses, and produce an immunogenic tumor microenvironment, successfully inhibiting CT26 tumor growth by eliciting a systemic ICD‐based antitumor immunity.
Strong and Tough Nanostructured Hydrogels and Organogels Prepared by Polymerization‐Induced Self‐Assembly
Authors: Zeng Zhong , Li Ziyun , Li Qili , Song Guangjie , Huo Meng 
Published: March 2023

AbstractIn nature, the hierarchical structure of biological tissues endows them with outstanding mechanics and elaborated functions. However, it remains a great challenge to construct biomimetic hydrogels with well‐defined nanostructures and good mechanical properties. Herein, polymerization‐induced self‐assembly (PISA) is for the first time exploited as a general strategy for nanostructured hydrogels and organogels with tailored nanodomains and outstanding mechanical properties. As a proof‐of‐concept, PISA of BAB triblock copolymer is used to fabricate hydrogels with precisely regulated spherical nanodomains. These nanostructured hydrogels are strong, tough, stretchable, and recoverable, with mechanical properties correlating to their nanostructure. The outstanding mechanical properties are ascribed to the unique network architecture, where the entanglements of the hydrophilic chains act as slip links that transmit the tension to the micellar crosslinkers, while the micellar crosslinkers dissipate the energy via reversible deformation and irreversible detachment of the constituting polymers. The general feasibility of the PISA strategy toward nanostructured gels is confirmed by the successful fabrication of nanostructured hydrogels, alcogels, poly(ethylene glycol) gels, and ionogels with various PISA formulations. This work has provided a general platform for the design and fabrication of biomimetic hydrogels and organogels with tailorable nanostructures and mechanics and will inspire the design of functional nanostructured gels.
Effect of Polymer Additives on the Crystal Habit of Metformin HCl
Authors: Bellucci Michael A. , Marx Anke , Wang Bing , Fang Liwen , Zhou Yunfei , Greenwell Chandler , Li Zhuhong , Becker Axel , Sun GuangXu , Brandenburg Jan Gerit , Sekharan Sivakumar 
Published: March 2023

AbstractThe crystal habit can have a profound influence on the physical properties of crystalline materials, and thus controlling the crystal morphology is of great practical relevance across many industries. Herein, this work investigates the effect of polymer additives on the crystal habit of metformin HCl with both experiments and computational methods with the aim of developing a combined screening approach for crystal morphology engineering. Crystallization experiments of metformin HCl are conducted in methanol and in an isopropanol‐water mixture (8:2 V/V). Polyethylene glycol, polyvinylpyrrolidone, Tween80, and hydroxypropyl methylcellulose polymer additives are used in low concentrations (1–2% w/w) in the experiments to study the effect they have on modifying the crystal habit. Additionally, this work has developed computational methods to characterize the morphology “landscape” and quantifies the overall effect of solvent and additives on the predicted crystal habits. Further analysis of the molecular dynamics simulations is used to rationalize the effect of additives on specific crystal faces. This work demonstrates that the effects of additives on the crystal habit are a result of their absorption and interactions with the slow growing {100} and {020} faces.
Phishing uniform resource locator detection using machine learning: A step towards secure system
Authors: Mahajan Shilpa 
Published: March 2023

AbstractThe advancement in technology has led to increase in cyber‐attacks. Hackers have become more skilled at finding the loopholes in the system and can penetrate easily on to host network. The rate of cybercrimes is increasing exponentially with the growth of digital era. Phishing is considered as one of the top cybercrimes that has impacted the society at large. As per Kaspersky reports 2021, around 22% attacks were phishing attacks. This paper explores methods for detecting phishing uniform resource locator (URLs) by analyzing various features using Machine Learning techniques. Various data mining algorithms are used to learn data patterns that can identify and differentiate between benign and phishing websites using phishing website data set. The best results are shown by an XGBoost Model that provides more than 90% accuracy on the balanced class dataset.
MyEasyHealthcare: An efficient and secure three‐tier blockchain‐based healthcare system
Authors: Agrawal Kanika , Aggarwal Mayank , Tanwar Sudeep 
Published: March 2023

AbstractBlockchain systems have seen vast growth due to the immense potential in developing secure applications for education, healthcare, and so forth. The healthcare system is extensively researched to provide convenience to human life. With the exponential growth in healthcare systems and devices, patient data security and privacy issues are becoming primary concerns. Blockchain is emerging as a solution to secure healthcare records, but it faces certain shortcomings like transaction time, execution time, gas cost consumption, bandwidth utilization, and so forth. The current article designed an extensive blockchain‐based healthcare system (MyEasyHealthcare) with reduced gas consumption, transaction cost, execution cost, and bandwidth utilization, along with enhanced security at three levels. At the first level, the professionals and patients get registered, which provides identity access management. Secondly, authorization is required for each registered entity by the owners. Lastly, the third level includes a doctor‐patient relationship where the hospital's owner assigns a patient to a particular doctor. The data is protected from the outer world and is preserved only between the doctor and the patient. Moreover, to include the majority of tasks for hospital management, the developed system incorporates a smart contract to record seven different parameters for patient diagnosis by a physician and 15 different parameters by a pathologist. The designed system is evaluated for the amount of gas consumed, transaction cost, execution cost, and bandwidth utilization by simulating/executing the written smart contract on InterPlanetary File System (IPFS) and Remix to check the feasibility of the developed system (MyEasyHealthcare) for the real world; the results testify the proposed system is useful in the real world.
Classroom as Neo‐National Microcosm: Teachers Learning to Disrupt Linguistic Microaggressions
Authors: Chang‐Bacon Chris K. , Salerno April S. 
Published: March 2023

AbstractNeo‐national ideologies are often associated with despots and political extremists. Yet, we argue that neo‐nationalist discourses also manifest in everyday TESOL classroom interactions. In English‐dominant contexts, teachers send potent messages about who does or does not “belong” in classrooms, largely based on racialized notions of English proficiency. These dynamics create a classroom microcosm where students are apprenticed into linguistic normativity and anti‐immigrant sentiments, ultimately sustaining future generations of neo‐nationalist rhetoric. In light of these dynamics, we believe that teachers can play a key role in disrupting normative, monolingual language ideologies in classrooms, but that they often feel underprepared to do so. In this brief research report, we present findings from our ongoing examination of TESOL licensure endorsement candidates responding to deficit‐oriented microaggressions about multilingual learners in a simulated environment. Our results suggest teacher candidates have the desire to promote asset‐based orientations around multilingualism, but are often unable to do so in real time. These findings have important implications for teacher education and the underutilized potential of teachers for disrupting deficit‐oriented monolingual discourses that too easily turn into neo‐nationalist ideologies.