bluuebunny/crossref_metadata_2025 huggingface dataset:
Higher-order topological corner states and origin in monolayer LaBrO
Authors: Wang 王 Qing 庆 , Hao 郝 Ning 宁
Published: October 2024

Intrinsic higher-order topological insulators driven solely by orbital coupling are rare in electronic materials. Here, we propose that monolayer LaBrO is an intrinsic two-dimensional second-order topological insulator. The generalized second-order topological phase arises from the coupling between the 5d orbital of the La atom and the 2p orbital of the O atom. The underlying physics can be thoroughly described by a four-band generalized higher-order topological model. Notably, the edge states and corner states of monolayer LaBrO exhibit different characteristics in terms of morphology, number, and location distribution under different boundary and nanocluster configurations. Furthermore, the higher-order topological corner states of monolayer LaBrO are robust against variations in spin–orbit coupling and different values of Hubbard U. This provides a material platform for studying intrinsic 2D second-order topological insulators.
Multi-feature Fusion Recognition Method of Rail Surface State Based on SVM Algorithm
Authors: Liu Lili , Zuo Jihong , Yang Chuanyin , Tang Yufeng
Published: October 2024

In order to solve the problems that the rail surface status is still judged by manual experience and the recognition efficiency is low, a multi-feature fusion recognition method of rail surface status based on SVM algorithm is proposed. First, the rail surface image database is obtained by preprocessing the collected rail surface images in different states. The preprocessing includes image graying, image denoising and image extraction. Then, the gray mean and variance of the contact surface region are calculated to describe the color features of the rail surface image. And the texture features of the contact surface region are extracted using the gray level co-occurrence matrix. Then the two features are fused as the basis for judging the rail surface state. SVM is used to recognize the rail surface state. Finally, the proposed method is verified and analyzed by experimental simulation, and the results prove the effectiveness of the proposed method.
VMD-BiGRU for Short-term Power Load Forecasting with Energy Valley Optimizer Enhancement
Authors: Lai Yibo , Wang Qifeng , Chen Gang , Sun Quan , Liao Xiaojing , Shen Zhilong , Bai Yu
Published: October 2024

Electrical load, given context of this modern era, is recognized to have distinct characteristics: diversity, flexibility, and inherently, non-linearity and temporality. Aiming to leverage these characteristics and counteract the challenges within, we propose an electrical load forecasting method, namely EVO-VMD-BiGRU. The proposed technique initiates by utilizing Variational Mode Decomposition (VMD) for the breakdown of the load data into constituent modes, extract the principal modes, and merge them with the features of air temperature, wind speed, precipitation, electricity price and holidays. The modes are then fed to the BiGRU model for training to forecast. The Energy Valley Optimizer (EVO) is applied to search for optimal hyperparameters of the BiGRU model, with the objective of minimizing the RMSE, in order to obtain models for each mode. Finally, the method utilizes these models to forecast the values of each mode, summing them to generate the final predictions. T The efficacy of this approach was confirmed through testing on load datasets sourced from Singapore and Australia. The proposed method achieved an RMSE of 81.20 MW and 30.15 MW on the respective datasets, the MAPE of 0.79% and 0.47%, and the R-squared (R2) of 0.99 and 0.99, which are superior to the alternative methods in the experiments. Results show that the proposed method achieves superior outcomes in short-term electricity load forecasting and exhibits promising potential for practical use.
Ship Lock Chamber Arrangement in Xiangjiang River Based on Artificial Bee Colony and Adaptive Genetic Algorithm
Authors: Deng Wei , Yan Shuting , Xie Zhenhua , Xu Xiaolong , Xiong Haoqi
Published: October 2024

To plan the ship lock chamber arrangement in Xiangjiang river, an artificial bee colony-adaptive genetic algorithm was proposed for the scheduling of the lock chamber, considering that the performance of the basic genetic algorithm relies on the quality of the initial population, the selection of genetic operators, crossover, and mutation operations. Firstly, the artificial bee colony algorithm was used to initialize the population to enhance population diversity. The utilization rate of the lock chamber and the waiting time for the lock were used as evaluation indicators for the fitness function. Then, adaptive strategies were designed to adjust the crossover and mutation operators to improve the convergence speed of the algorithm. Experimental results showed that, in a Xiangjiang river ship lock chamber with a size of 280 m×34 m, the average number of ships selected by the proposed artificial bee colony-adaptive genetic algorithm was 2 more than that of manual scheduling and 1.5 more than that of the genetic algorithm. The utilization rate of the lock chamber scheduling was increased by 13.01% compared to manual scheduling and by 5.4% compared to the genetic algorithm. The average waiting time for the lock was reduced by 1.3 hours compared to manual scheduling and by 0.8 hours compared to the genetic algorithm. It effectively improves the efficiency of ship traffic and optimizes the utilization of the lock chamber, making it practical for real-world applications.
Analysis and Research on Farmland Use Changes in Changchun City Based on ArcGis Remote Sensing Images
Authors: Chen Hang , Zhao Liya , Dong QingQi , Chen Guifen
Published: October 2024

Land is an essential basis for the sustained existence and development of human beings, arable land resources are the fundamental guarantee of food replenishment, contemporary scholars also put forward high requirements for the study of remote sensing image feature type classification extraction, the study of remote sensing image feature type classification and algorithms are very necessary. Therefore, based on remote sensing image data, this paper combines supervised classification with unsupervised classification, selects the advantages of the algorithm and improves it, refers to the classification system to select the classification standard, improves the support vector machine algorithm and compares it with other classification algorithms to improve the classification accuracy. Firstly, unsupervised classification is used to extract forest land, cultivated land and grassland into one category, and then secondary extraction is used to classify and subdivide them with SVM classification in supervised classification. Through conducting experiments on image data over a period of three years, the information of cultivated land is extracted from the remotely sensed image data of Changchun City in the years 2000, 2010, and 2020. By observing the change trend of land use, it is found that the cultivated land in Changchun City demonstrates a decreasing tendency from 2000 to 2020. Finally, it is concluded that Changchun’s cultivated land shows a decreasing trend from 2000 to 2020. Finally, this paper takes ten years as a gradient and obtains remote sensing image data in three time periods to analyze the change of cropland utilization. The results show that the method is effective in practical application and can save human and material resources to analyze the type of feature data.
Research on Differential Protection of Distribution Network Based on 5G Communication Technology
Authors: Chen Weijun , Yao Haiyan , Yu Xiaoling , Chen Hao
Published: October 2024

The application of traditional optical fiber in differential protection technology in distribution networks faces many challenges. Due to the physical characteristics and transmission limitations of optical fiber, there is a blind area for line fault isolation, which cannot meet the growing demand for access, and is not conducive to the popularization and application of differential protection in distribution networks. This paper proposes a differential protection method for distribution networks based on 5G communication technology. 5G communication technology has the characteristics of high bandwidth, low delay, high precision network timing and safety and reliability, and provides a new wireless communication method for differential protection of distribution network. The introduction of 5G communication technology can not only provide a more stable and fast data transmission channel to ensure that the differential protection system can respond quickly after receiving the fault signal, but also realize the precise monitoring of each node of the distribution network. At the same time, this paper combines network slicing technology, uplink scheduling optimization, bit error rate optimization, air retransmission optimization, transmission priority optimization and other methods to reduce the communication delay and delay jitter, improve the reliability of the method.
Identification Source Term of the Distributed Order Time-Space Fractional Diffusion Equation
Authors: Piao Yuhao , Li Yushan
Published: October 2024

The inverse source problem for time-distributed order spatial fractional diffusion equations is examined in this study. The forward problem is solved by combining finite difference methods with matrix transformation techniques. The Tikhonov regularization approach is then applied to convert the inverse problem into a variational problem. The optimal perturbation approach is used to find the minimizer of the variational problem, leading to an approximation solution that depends solely on the time-dependent source term. The algorithm’s effectiveness and stability are demonstrated using numerical examples in one-dimensional domains.
Open Domain Target Detection Based on Image-text Alignment Large Model under Railway Smart Construction Site
Authors: Wang Yaoguo
Published: October 2024

Open domain target detection plays a crucial role in ensuring people’s life safety in Railway Smart Construction Site. This paper proposes a target detection method that is not limited by the number of labels, which is different from traditional models that are usually trained and tested on a fixed set of object categories (or a set of labels). Firstly, the pre-training GLIP model is utilized to train the collected image-text pairing data to generate grounding boxes. Secondly, the pseudo-labeled data formed by associating these boxes with the corresponding text descriptions were combined with the original image-text data to form an enhanced dataset. The final model performs inference based on the prompt and incoming image data to determine the localization information. The GLIP model effectively aligns image and text information and enhances its ability to recognize and handle problems by observing and understanding new situations.
A Knowledge Distillation Method Based on Evidence Theory to Prevent Catastrophic Forgetting
Authors: Peng Bo , Jang Feng , Wang Shen , Li Zhou , Zhang Shizhe , Li Mengyu , Liu Yonghe , Zhao Wei , Jia Min
Published: October 2024

Incremental learning is an emerging machine-learning approach designed to prevent catastrophic forgetting while learning a new task with knowledge retained from previous tasks. However, existing methods often must fully utilize the distributional information of the old task model’s outputs. To alleviate this, we propose a class incremental learning method grounded in evidence theory to leverage the distributional information of outputs from the old task model, which integrates uncertainty estimation into the knowledge distillation process to ensure the new task model effectively learns from the old task model’s distribution information. Specifically, we incorporate uncertainty estimation based on evidence theory to calculate knowledge distillation loss during training. We compute the uncertainty estimates of outputs from both the new and old task models, and then they are used in the knowledge distillation loss calculation. We propose a novel classification strategy that considers outputs’ probability and uncertainty estimates, which could determine the sample category without requiring an additional training phase or supplementary models. Experiments on the CIFAR-100 and ImageNet datasets demonstrate the effectiveness of the proposed method, showing that it outperforms existing methods by improving accuracy by 1%-2%. Results suggest that leveraging the distribution information of model outputs can effectively mitigate catastrophic forgetting in deep learning models within incremental learning scenarios.
The case classification and their development for would-be mathematics teachers’ training
Authors: Achkan V V , Vlasenko K V , Lovianova I V , Yu Kaluhin R , Armash T S
Published: October 2024

The article looks into the issue of the case classification for the training of Mathematics teachers. The analysis, which was carried out, and the survey of 47 University teachers of methodical disciplines allowed to highlight the classification features of cases in the process of teaching methodical disciplines: the amount of time to complete, the way of presentation, the level of complexity and the breadth of the covered problem. Classifying cases by the amount of time for their implementation contributed to the separation of mini-cases, medium-term cases, and long-term cases. Classification by the method of presentation of cases in the process of studying methodical disciplines ensured their use in printed (handwritten) form, multimedia presentation of cases, and video cases. According to the level of complexity, the cases were divided into reproductive-training, partial-research, and creative-innovative cases. Thematic and integrated cases ensured the breadth of coverage of the problem during the teaching of methodical disciplines. The article presents general requirements for the selection and development of cases in the process of studying methodical disciplines. These requirements are based on the principles of accessibility, scientificity, contextuality, systematicity, methodological expediency, and practical orientation. The classification and specific requirements became the basis for the development of cases that can be used in the process of teaching methodological disciplines of would-be Mathematics teachers.
Analytical and geometric interpretation of the flat arrangement of points by means of metric geometry in the study of metric spaces
Authors: Kuz’mich V I , Kuzmich L V , Savchenko A G , Valko K V
Published: October 2024

When studying metric spaces, students of higher education often have difficulties with understanding the basic concepts and properties of these spaces. This, to a large extent, is a consequence of the significant level of formalization of such concepts on the one hand, and the preservation of the corresponding formulations and names familiar to students from a school mathematics course. To overcome these difficulties, it is advisable to use methods of geometric interpretation and visualization of these properties. At the same time, it is appropriate to use elements of metric geometry. Its methods make it possible to interpret the geometric features of the mutual placement of points of metric space in Cartesian (rectangular) coordinate systems, which are familiar to students of higher education. Moreover, it becomes possible to visualize these features with the help of graphic editors, since they, as a rule, use numerical values of the coordinates of points to visualize them. Based on the definition of an angle as an ordered trio of points of an arbitrary metric space, and the angular characteristic of this angle, the fact of the flat placement of four points of a non-Euclidean metric space is established, and examples of digital visualization of this arrangement using the dynamic geometric environment GeoGebra 3D are given.
Nanoart in STEAM education: Combining the microscopic and the creative
Authors: Suchikova Y O , Kovachov S S
Published: October 2024

This article explores the integration of Nanoart within the STEAM (Science, Technology, Engineering, Art, and Mathematics) education framework, highlighting its pivotal role in enhancing interdisciplinary learning. Through a detailed examination of a project-based learning (PBL) initiative, the study showcases students specializing in “Applied Physics and Nanomaterials” engaging in creating nanostructures via electrochemical etching and their subsequent transformation into Nanoart. This educational endeavor exemplifies the seamless integration of STEAM components—combining scientific principles, technological application, engineering design, artistic creativity, and mathematical precision—and significantly deepens students’ understanding of these elements. The article details each project phase, from conceptualization through execution, illustrating how students navigate the complexities of nanoscience and apply their interdisciplinary knowledge to produce tangible artistic and scientific outcomes. By transforming abstract scientific concepts into visually and intellectually stimulating Nanoart, the project encourages creative thinking and innovation among students. It further demonstrates how integrating art into STEM subjects can make scientific education more accessible and engaging, attracting a more comprehensive array of students and enriching their academic and practical experiences. Additionally, the study discusses the broader implications of Nanoart in STEAM education, emphasizing its effectiveness in bridging the gap between scientific exploration and artistic expression. It argues that this approach not only demystifies complex concepts but also fosters a holistic educational environment that prepares students to think critically and creatively across disciplines.
Naphthylated LEGO-lipophosphonoxin antibiotics used as a fluorescent tool for the observation of target membrane perturbations preceding its disruption
Authors: Dolejšová Tereza , Lišková Petra , Sahatsapan Nitjawan , Mojr Viktor , Pohl Radek , Brzobohatá Hana , Dugić Milica , Křížek Tomáš , Cwiklik Lukasz , Mikušová Gabriela , Rejman Dominik , Fišer Radovan
Published: October 2024

Linker-Evolved-Group-Optimized-Lipophosphonoxins (LEGO-LPPO) are small synthetic modular peptidomimetics with promising antimicrobial activity. The LEGO-LPPO mechanism of antibacterial action has been determined to be the depolarization and disruption of bacterial membranes. Their modular nature is advantageous for fine tuning their biological properties. In order to optimize the structure of LEGO-LPPO even further, it is important to understand the interaction of LEGO-LPPO with bacterial membranes at the molecular level. In this work, we present the synthesis of five LEGO-LPPO (designated as 1_naph2-4-G to 5_naph2-4-G) molecules bearing fluorescent naphtylethyl moieties and their usage in the study of LEGO-LPPO behaviour in the membrane. Our goal was to characterize fluorescently labelled LEGO-LPPO under conditions that do not completely disrupt the membrane, mostly in the form of membrane-bound monomers. We observed the intramolecular interactions of hydrophobic modules of 1_naph2-4-G in the buffer by detecting dynamic naphthyl excimers and their disappearance after 1_naph2-4-G bind into the membranes. In the membrane, the molecule 1_naph2-4-G slightly affects the membrane fluidity of DOPG membranes above the phase transition. The naphthyl fluorophore itself has fast and almost unrestricted rotation around ethylene linking groups (r

inf
= 0.010), which indicates a considerable chaotropic effect of the hydrophobic modules of 1_naph2-4-G at the given depth of the membrane. 1_naph2-4-G proved to be a useful model for observing the interaction of LEGO-LPPO antibiotics with the phospholipid bilayer enabling us to decipher its effects on membrane state and dynamics; its binding and penetration into the membrane, its structure and the particular depth that it occupies.
Recent advances in electrode optimization of electrochemical energy devices using topology optimization
Authors: Alizadeh Mehrzad , Charoen-Amornkitt Patcharawat , Suzuki Takahiro , Tsushima Shohji
Published: October 2024

Topology optimization (TO) has emerged as a prominent trend in recent years, driven by its ability to explore optimized material distributions from scratch. Recently, there has been a significant shift in the application of TO, in optimizing systems involving complex electrochemical reactions, particularly electrode porous structures. This paper aims to examine the utilization of TO in enhancing electrodes across various electrochemical energy devices (EEDs). It encompasses a broad spectrum of applications, including the optimization of porous electrodes through the density-based method and interfaces between electrodes and electrolytes through the level-set method. The paper will delve into the challenges and opportunities associated with employing TO in electrode design for EEDs. These challenges involve addressing computational complexity, the absence of theoretical foundations for optimized structures, and the fabrication of complex structures for practical real-world applications. Additionally, beyond TO, the paper will spotlight other notable techniques in the structural design of porous electrodes using mathematical optimization. By offering insights into state-of-the-art research and developments in TO’s application to electrode design, this paper provides researchers with valuable resources to navigate the evolving landscape of electrode design for EEDs.
Introduction
Authors: Kerr Orin
Published: October 2024

The widespread use of computers and the Internet calls for new rules under the Fourth Amendment, the constitutional ban on unreasonable searches and seizures. In the US constitutional system, the Supreme Court and lower courts interpret the Fourth Amendment to limit how the police gather information. But computers call for new Fourth Amendment rules. Much like the automobile changed Fourth Amendment law in the twentieth century, computers must change Fourth Amendment law in the twenty-first century. Courts must craft a new Digital Fourth Amendment, adopting rules that preserve the traditional function of the Fourth Amendment for the new world of computers.
Digital Evidence
Authors: Kerr Orin
Published: October 2024

Computers present a fundamental challenge to Fourth Amendment law because digital evidence is different from physical evidence. Almost everyone uses computers and the Internet, and computers store a remarkable amount of information about what its users do. Skilled specialists who are experts in the field of computer forensics can often recover detailed information about past events, including past crimes. In some cases, the evidence is in local machines such as cell phones and laptop computers. In other cases, the evidence is held by Internet providers such as Google. Criminal investigators can go to these providers and obtain records without users even being aware of their access under a law called the Stored Communications Act. Current Fourth Amendment law is not ready for these new digital facts. Applying the old rules of Fourth Amendment law to the new facts of digital evidence ends up dramatically expanding government power.
Searches and Seizures
Authors: Kerr Orin
Published: October 2024

The Fourth Amendment prohibits unreasonable “searches” and “seizures,” and the first major question raised by the Digital Fourth Amendment is how these terms should be interpreted in the stand-alone setting of local digital storage devices. What does it mean to “search” a digital file, or to “seize” it? By relying on the container analogy, seeing digital storage devices as akin to physical containers, we can start with the notion that accessing data from a storage device is a search. Courts should adopt an exposure-based bright-line rule: Retrieving data and exposing it to outside observation is a search of the data that is exposed. Courts should also treat digital copies as the original; if forensic experts copy a file and then retrieve data from it, that is also a search. Finally, copying Fourth Amendment–protected data should ordinarily be a seizure of that data. This test raises special problems for Internet preservation under the Stored Communications Act. When government agents order an Internet provider to save a copy of a person’s account, and the company responds by copying the file, that process “seizes” the data and the seizure should be permitted only when it is reasonable.
Warrants for Digital Evidence
Authors: Kerr Orin
Published: October 2024

A critical question for the Digital Fourth Amendment is the law of digital warrants. When a computer is searched with a warrant, an extraordinary amount of personal information comes into plain view. As a practical matter, there’s a needle-in-the-haystack problem: Investigators need to look through the entire haystack to find the needle. But if the courts stick with traditional Fourth Amendment rules, digital warrants may become general warrants in practice—the exact problem that the Fourth Amendment was enacted to solve. The question becomes, “How should courts solve this problem?” The answer is to impose use restrictions. With a warrant, investigators should be able to search through the entire computer for responsive evidence named in the warrant. But the discovery of nonresponsive evidence—evidence not named in the warrant as an item to be seized—should not be able to be disclosed to the public or used in a criminal case. This new approach achieves the best balance for the facts of computer searches: It lets the government find the needle in the haystack, but it ensures that the government doesn’t have unlimited access to and use of everything else in the haystack.
Border Searches
Authors: Kerr Orin
Published: October 2024

Should the Fourth Amendment allow the federal government to search computers and cell phones that cross the U.S. border without a warrant? In the traditional physical setting, the Supreme Court has recognized a broad border search exception to the Fourth Amendment warrant requirement: most searches of property require no suspicion at all. Courts should reject this rule when it comes to digital devices, however. When a US citizen crosses the border with a cell phone, laptop, or other digital storage media, the government should be required to have the same search warrant to search the device that is required inside the United States. Courts should reject the border search exception for digital devices for the same reason that the Supreme Court rejected the search-incident-to-arrest exception for warrantless searches of cell phones in Riley v. California: the rationale for the exception is rooted in the physical world, and it does not extend to digital media. A different rule might be needed for the devices of noncitizens, but that is a complicated question that must be left for another day.
Epilogue
Authors: Kerr Orin
Published: October 2024

The Digital Fourth Amendment is alive. Courts are handing down new cases regularly, and the law continues to evolve. The Supreme Court has been quiet in this area since Carpenter: it is on an unusual Fourth Amendment hiatus. But the hiatus will end eventually, and the Supreme Court will then step in and address how the Fourth Amendment applies to the digital realm. Several circuit splits exist already, clearing the way to Supreme Court review, on issues such as the border search exception and the mosaic theory. Over time, the Supreme Court will craft a Digital Fourth Amendment for the modern age.
Early German Positivism
Authors: Beiser Frederick C
Published: October 2024

This book is an attempt to recover a neglected chapter of the history of philosophy: the history of early German positivism, 1860–1914. It treats figures almost completely forgotten in the German and Anglo-American worlds: Theodor Gomperz (1832–1912), Eugen Dühring (1833–1921), Ernst Laas (1837–85), and Friedrich Jodl (1849–1914); it also examines Ernst Mach (1838–1916) and Richard Avenarius (1843–1896), who are much better known but contemporaries of these thinkers. The first four of these figures became famous, and published their major works, before the formation of the (first) Vienna Circle in 1912. Several positivist themes unite these thinkers: rejection of the synthetic a priori; opposition to pessimism; a philosophy of monism, naturalism, and historicism; and the belief that the highest good can be achieved only under the guidance of science. Positivism was thus a continuation of the Enlightenment into the 20th century. The examination of early positivism makes it necessary to question several claims made about positivism by Michael Friedman: that the positivists’ main concerns did not arise within the empiricist tradition; that the positivist rejection of the synthetic a priori arose from developments in geometry; that there is no foundationalism within positivism. Placing positivism in this broader intellectual context makes all these claims questionable. The aim throughout is to place positivism in a wider intellectual context, which goes back to the Enlightenment and the opposition to the Christian tradition.
Eugen Dühring
Authors: Beiser Frederick C
Published: October 2024

Dühring was the father of German positivism. His Natürliche Dialektik states many of the central themes of positivism: the unity of science; rejection of metaphysics; the defense of empiricism; the rejection of the synthetic a priori; the orientation of philosophy around the empirical sciences. Dühring was an admirer of Comte, and his major work, Cursus der Philosophie, was modeled around Comte’s Cours de philosohie positive. This chapter examines several aspects of Dühring’s philosophy: his critique of Schopenhauer’s pessimism; his naturalism and materialism; his philosophy of science; and his dispute with Friedrich Engels.
Marital Status Discrimination in India
Authors: Ghosh Arijeet , Sanyal* Diksha
Published: October 2024

Marital status discrimination, like race and sex, is a ground for discrimination in many jurisdictions. In India however, such a ground has neither been constitutionally nor statutorily recognized. With recent attempts by civil society to advocate for an anti-discrimination law, such a ground could, however, become a part of the legal system. This chapter identifies laws and policies across the domains of family, health, labour, welfare, and citizenship that privilege heterosexual, monogamous, married couples in India directly or indirectly. Thereafter, we attempt to analyse whether recognizing marital discrimination statutorily or constitutionally could be a potential way to challenge the discrimination experienced by non-heterosexual, non-marital couples, and single individuals. By undertaking a textual analysis of these central laws and policies, we aim to describe how marriage is entrenched in Indian legal discourse and the extent to which recognizing marital status as a ground could correct this.
Using Overlap Weights to Address Extreme Propensity Scores in Estimating Restricted Mean Counterfactual Survival Times
Authors: Cao Zhiqiang , Ghazi Lama , Mastrogiacomo Claudia , Forastiere Laura , Wilson F Perry , Li Fan
Published: October 2024

While inverse probability of treatment weighting (IPTW) is a commonly used approach for treatment comparisons in observational data, the resulting estimates may be subject to bias and excessively large variance under lack of overlap. By smoothly down-weighting units with extreme propensity scores, i.e., those that are close (or equal) to zero or one, overlap weighting (OW) can help mitigate the bias and variance issues associated with IPTW. Although theoretical and simulation results have supported the use of OW with continuous and binary outcomes, its performance with survival outcomes remains to be further investigated, especially when the target estimand is defined based on the restricted mean survival time (RMST). We combine propensity score weighting and inverse probability of censoring weighting to estimate the restricted mean counterfactual survival times, and provide computationally-efficient variance estimators when the propensity scores are estimated by logistic regression and the censoring process is estimated by Cox regression. We conduct simulations to compare the performance of weighting methods in terms of bias, variance, and 95% interval coverage, under various degrees of overlap. Under moderate and weak overlap, we demonstrate the advantage of OW over IPTW, trimming and truncation, with respect to bias, variance, and coverage when estimating RMST.
Board of Pharmacy Specialties 2022 recertification data: Characteristics and perceptions of pharmacists successfully recertified
Authors: LaNou Elizabeth , Meng Yu , Patel Parth , Saiar Amin , Bakken Brianne K
Published: October 2024

Purpose

The purpose of this retrospective study was to utilize existing data to (1) compare the characteristics of Board of Pharmacy Specialties (BPS) credentials successfully recertified vs those that were not successfully recertified in 2022 and (2) compare survey responses about maintaining board certification by continuing pharmacy education (CPE) vs examination among those who successfully recertified.

The characteristics of BPS credentials eligible for recertification in 2022 (n = 4,812) and survey responses from board-certified pharmacists who successfully recertified in 2022 (n = 3,629) were retrieved from the MyBPS database. Across all specialties, 75.4% of credentials were successfully recertified in 2022. Most credentials were recertified by CPE (92.1%). Successfully recertified credentials were predominately held by pharmacists practicing within the US (96.7%), those between the ages of 31 and 40 years (51.9%), and those completing the first 7-year certification cycle (73.9%). A significant difference was found between recertified credentials and those that were not recertified based on specialty, recertification pathway, credential holder practice location, and credential holder age. Over 89% of respondents reported that a primary benefit of maintaining board certification is to “expand knowledge and skills in pharmacy.”

Conclusion

Several factors influence the decision and/or ability of board-certified pharmacists to recertify and maintain their credentials. Successfully recertified board-certified pharmacists report expanded competency, credibility, personal gratification, and increased confidence among the primary benefits of maintaining board certification. Board-certified pharmacists who successfully recertify also report a preference for a recertification process that is temporally and financially efficient.
Long-term management of moderate-to-severe atopic dermatitis with lebrikizumab and concomitant topical corticosteroids: a 68-week randomized double-blind placebo-controlled phase III trial in Japan (ADhere-J)
Authors: Katoh Norito , Tanaka Akio , Takahashi Hidetoshi , Shimizu Ryosuke , Kataoka Yoko , Torisu-Itakura Hitoe , Morisaki Yoji , Yamamoto Chie , Igawa Ken
Published: October 2024

Background

Moderate-to-severe atopic dermatitis (AD) affects the quality of life of patients. More treatment options are urgently needed to manage this chronic disease. Lebrikizumab is a monoclonal antibody that binds to interleukin-13, a key mediator in AD pathogenesis. In Japanese patients, lebrikizumab has been evaluated through week 16 in the randomized placebo-controlled phase III ADhere-J study.

Objectives

To evaluate the long-term efficacy and safety of lebrikizumab in combination with topical corticosteroids (TCS) in the ADhere-J study.

Methods

Patients aged ≥12 years weighing ≥ 40 kg with moderate-to-severe AD and receiving either subcutaneous lebrikizumab 250 mg ­every 2 weeks (Q2W)/every 4 weeks (Q4W) or placebo during the 16-week induction period were evaluated during the long-term maintenance period from week 16 to week 68. Responders achieved the co-primary endpoints at week 16: an Investigator’s Global Assessment score of 0 or 1 [IGA (0,1)] with ≥ 2-point improvement from baseline and/or ≥ 75% improvement from baseline in Eczema Area and Severity Index (EASI 75). In this analysis, week 16 responders received lebrikizumab 250 mg Q2W or Q4W combined with TCS during the maintenance period (maintenance primary population; MPP); week 16 per-protocol nonresponders received lebrikizumab Q2W with TCS (maintenance escape population; MEP). Major endpoints included IGA (0,1) with ≥ 2-point improvement from baseline and EASI 75 through week 68. Other outcomes included quality of life, itch and serum thymus and activation-regulated chemokine. The trial was registered with ClinicalTrials.gov (NCT04760314).

Results

At week 68, 66–81% of 103 patients in the MPP and 32–38% of 168 patients in the MEP achieved IGA (0,1) with ≥ 2-point improvement from baseline. EASI 75 was maintained by 83–89% of patients in the MPP, while 71–80% of patients in the MEP achieved this outcome by week 68. Across treatment arms, patients in the MPP tended to maintain improvements recorded at week 16, while patients in the MEP steadily improved across the maintenance period. No new safety signals were reported, and most treatment-emergent adverse events were mild or moderate in severity in both populations. Safety outcomes were consistent with previous reports for lebrikizumab treatment in global studies.

Conclusions

These results support the use of lebrikizumab in combination with TCS for the treatment of moderate-to-severe AD in the Japanese population in the long term.
α2δ-2 regulates synaptic GluK1 kainate receptors in Purkinje cells and motor coordination
Authors: Zhou Meng-Hua , Zhou Jing-Jing , Chen Shao-Rui , Chen Hong , Jin Daozhong , Huang Yuying , Shao Jian-Ying , Pan Hui-Lin
Published: October 2024

Gabapentin and pregabalin are inhibitory ligands of both α2δ-1 and α2δ-2 proteins (also known as subunits of voltage-activated Ca2+ channels) and are commonly prescribed for the treatment of neuropathic pain and epilepsy. However, these drugs can cause gait disorders and ataxia through unknown mechanisms. α2δ-2 and GluK1, a glutamate-gated kainate receptor subtype, are coexpressed in cerebellar Purkinje cells. In this study, we used a heterologous expression system and Purkinje cells to investigate the potential role of α2δ-2 in regulating GluK1-containing kainate receptor activity.

Whole-cell patch-clamp recordings showed that α2δ-2 coexpression augmented GluK1, but not GluK2, currents in HEK293 cells, and pregabalin abolished this augmentation. Pregabalin lost its inhibitory effect on GluK1 currents in HEK293 cells expressing both GluK1 and the α2δ-2(R282A) mutant. Blocking GluK1-containing receptors with UBP310 substantially reduced the amplitude of excitatory post-synaptic currents at parallel fibre–Purkinje cell synapses in mice. Also, pregabalin markedly attenuated the amplitude of excitatory post-synaptic currents and currents elicited by ATPA, a selective GluK1 receptor agonist, in Purkinje cells in Cacna2d1 knockout mice. Co-immunoprecipitation assays indicated that α2δ-2, but not α2δ-1, formed a protein complex with GluK1 in cerebellar tissues and HEK293 cells through its C-terminus. Furthermore, α2δ-2 coexpression potentiated surface expression of GluK1 proteins in HEK293 cells, whereas pregabalin reduced GluK1 proteins in cerebellar synaptosomes.

Disrupting α2δ-2–GluK1 interactions using α2δ-2 C-terminus peptide abrogated the potentiating effect of α2δ-2 on GluK1 currents and attenuated the amplitude of GluK1-mediated excitatory post-synaptic currents in Purkinje cells. However, neither pregabalin nor α2δ-2 C-terminus peptide had significant effect on P/Q-type currents in HEK293 cells. Additionally, CRISPR/Cas9-induced conditional knockdown of Cacna2d2 or Grik1 in Purkinje cells, in addition to microinjection of α2δ-2 C-terminus peptide or UBP310 into the cerebellum, substantially impaired beam-walking and rotarod performance in mice.

Our study reveals that α2δ-2 directly interacts with GluK1 independently of its conventional role as a voltage-activated Ca2+ channel subunit. α2δ-2 regulates motor coordination by promoting synaptic expression and activity in GluK1-containing kainate receptors in Purkinje cells.
Adult-onset female focal segmental glomerulosclerosis with nephrotic syndrome caused by a TBC1D8B variant: a case report
Authors: Hu Xiaoying , Cheng Wenrong , Xu Xiaoyi , Sun Lijun , Wang Guoqin , Cheng Hong
Published: October 2024

We report the case of a 49-year-old Chinese woman with nephrotic syndrome, characterized by normal kidney function but poor response to hormonal and immunosuppressive therapy, indicative of steroid-resistant nephrotic syndrome. Through renal biopsy, the patient was diagnosed as havingfocal segmental glomerulosclerosis (perihilar type), and subsequent whole-exome sequencing identified a pathogenic frameshift variant concerning the TBC domain of the TBC1D8B gene. This patient represents the first late-onset Chinese female who was found to carry a novel, pathogenic variant in the gene TBC1D8B.
Real-World Experience of the Association of HLADQA1*05 Allele With Loss of Response to Anti-TNF Inhibitors
Authors: Chokshi Aastha , Raker Christina A , Fine Sean
Published: October 2024

Background

Antitumor necrosis factor (anti-TNF) biologics have revolutionized the treatment of inflammatory bowel disease (IBD). Previously, studies have shown an association between the HLADQA1*05 allele and the development of antibodies and were predictive of loss of response. We sought to investigate the rate of the HLADQA1*05 allele in patients with IBD at a New England center and its association with antibody development and discontinuation of anti-TNF therapy.

Methods

A single center retrospective cohort study with patients on anti-TNF inhibitor therapy being followed at our IBD clinic who had testing performed for the HLADQA1*05 allele were identified and separated into 2 different groups: HLADQA1*05 positive (HLA carriers) or HLADQA1*05 negative (HLA noncarriers). Persistence of remaining on anti-TNF therapy, measurement of drug/antibody levels, and need for dose escalation were collected and stratified amongst the 2 groups.

Results

The prevalence of the HLADQA1*05 allele among all IBD patients followed was 53%. We identified 67 IBD patients being treated with anti-TNF medications, 46 (69%) patients with Crohn’s disease and 21 (31%) with ulcerative colitis. Most of the HLA carriers (85%) and HLA noncarriers (92%) remained on anti-TNF therapy at the end of the study period. Thirty-six (84%) patients had therapeutic drug monitoring performed during maintenance therapy. Three patients in the HLA carrier group had meaningful antidrug antibody levels necessitating cessation of therapy compared to one patient in the HLA noncarrier group (P = .61). Only 3 (13%) of HLA carriers and 4 (21%) of HLA noncarriers were on combination therapy with an immunomodulator. 65% of HLA carriers required dose escalation compared to 50% of HLA noncarriers (P = .70).

Conclusions

The prevalence of the HLADQA1*05 allele was 53% in our New England IBD patient population, similar to what has previously been reported in European studies. The majority of patients remained on anti-TNF therapy at the end of the study period despite carrier status. While there was a trend toward increased need for dose escalation among HLA carriers, this was not statistically significant. Future studies are needed to determine if the presence of the HLADQA1*05 allele leads to antibody development against anti-TNF inhibitors and treatment failure in patients with IBD.
Oral sarcoidosis preceding sudden cardiac arrest: a case report
Authors: Swain William , Castrichini Matteo , Siontis Konstantinos , Hasan Fadi , Arment Courtney
Published: October 2024

Background

Sarcoidosis is a disease characterized by non-caseating granulomas and may affect any organ system. Cardiac involvement may lead to conduction abnormalities, heart failure, or malignant ventricular arrhythmias. As sarcoidosis may present with heterogeneous manifestations, a detailed past medical history may provide clues that help guide further workup. We present a rare case of a patient with undiagnosed oral sarcoidosis who subsequently experienced cardiac arrest from cardiac involvement.

Case summary

A 43-year-old male with a history of palpitations and periodontitis consistent with oral sarcoidosis presents after experiencing sudden cardiac arrest. He was subsequently diagnosed with cardiac and pulmonary sarcoidosis. With contemporary management (both immunosuppression and antiarrhythmics), he has not experienced any recurrent arrhythmias.

Discussion

In the setting of cardiac arrest and non-ischaemic cardiomyopathy, a careful clinical history and targeted cardiac testing may help clinicians determine when to consider cardiac sarcoidosis as a diagnosis. While oral sarcoidosis is a very rare condition, this case highlights how infrequent manifestations of sarcoidosis may be encountered in the clinical setting.
Prediction of new-onset atrial fibrillation in patients with hypertrophic cardiomyopathy using plasma proteomics profiling
Authors: Lumish Heidi S , Harano Nina , Liang Lusha W , Hasegawa Kohei , Maurer Mathew S , Tower-Rader Albree , Fifer Michael A , Reilly Muredach P , Shimada Yuichi J
Published: October 2024

Aims

Atrial fibrillation (AF) is the most common sustained arrhythmia among patients with hypertrophic cardiomyopathy (HCM), increasing symptom burden and stroke risk. We aimed to construct a plasma proteomics-based model to predict new-onset AF in patients with HCM and determine dysregulated signalling pathways.

Methods and results

In this prospective, multi-centre cohort study, we conducted plasma proteomics profiling of 4986 proteins at enrolment. We developed a proteomics-based machine learning model to predict new-onset AF using samples from one institution (training set) and tested its predictive ability using independent samples from another institution (test set). We performed a survival analysis to compare the risk of new-onset AF among high- and low-risk groups in the test set. We performed pathway analysis of proteins significantly (univariable P < 0.05) associated with new-onset AF using a false discovery rate (FDR) threshold of 0.001. The study included 284 patients with HCM (training set: 193, test set: 91). Thirty-seven (13%) patients developed AF during median follow-up of 3.2 years [25–75 percentile: 1.8–5.2]. Using the proteomics-based prediction model developed in the training set, the area under the receiver operating characteristic curve was 0.89 (95% confidence interval 0.78–0.99) in the test set. In the test set, patients categorized as high risk had a higher rate of developing new-onset AF (log-rank P = 0.002). The Ras-MAPK pathway was dysregulated in patients who developed incident AF during follow-up (FDR < 1.0 × 10−6).

Conclusion

This is the first study to demonstrate the ability of plasma proteomics to predict new-onset AF in HCM and identify dysregulated signalling pathways.