bluuebunny/crossref_metadata_2025 huggingface dataset:
K-PD Modeling of Plozasiran - Mixed Hyperlipidemia
Authors: Gosselin Nathalie , Shi Jack
Published: February 2025

Background: Apolipoprotein C3 (APOC3), a component of triglyceride-rich lipoproteins (TRL), inhibits metabolism of TRLs through both inhibition of lipoprotein lipase (LPL) and reduced liver uptake of TRL remnants. Plozasiran (ARO-APOC3) is a GalNAc-siRNA designed to degrade hepatic APOC3 mRNA transcripts and reduce the production of APOC3 protein with expected reductions in serum triglycerides (TG) and TRL. In a Phase 2b clinical study conducted in 324 patients with mixed dyslipidemia (MD; TG 150-499 mg/dL, LDL-C ≥70 mg/dL or non-HDL-C ≥100 mg/dL), plozasiran doses of 10, 25 and 50 mg administered subcutaneously on Day 1 and Week 12 (1 additional 50 mg cohort on Week 24) during the double-blind period and subsequent Q12/24W dosing in the extension portion demonstrated substantial, dose-dependent and durable reductions in TG and in non-HDL-C and ApoB, two markers of atherogenic lipoproteins, supporting the initiation of a pivotal Phase 3 study with plozasiran in patients with mixed hyperlipidemia.Methods: Due to the major disconnect between plozasiran’s relatively short plasma exposures and its prolonged pharmacodynamic (PD) effects, its PD effects were best described by a kinetic-pharmacodynamic (K-PD) model. Potential impact of intrinsic and extrinsic factors was evaluated using standard covariate search techniques involving forward addition and backward elimination adjudicated by pre-specified statistical criteria. Model-based dose simulations were conducted to support selecting a Phase 3 dose regimen.Results: Reductions in APOC3, TG, ApoB and non-HDL-C by plozasiran were well described by a two-step, cascading, indirect-response population K-PD model, in which plozasiran, in the effect compartment (liver), inhibits APOC3 biosynthesis, thereby increasing the rates of clearance of TG and TRLs. Hepatic plozasiran is eliminated with an estimated t1/2 of 84 days in MD subjects, which helps explain its long PD action. Plozasiran IC50 dose was estimated to be 4.8 mg for a patient of median weight. The weight effect on PD was moderate and does not support weight-based dosing. No relevant differences were observed for other covariates including race, hepatic/renal functions, diabetic status and obese categories. A small improvement in non-HDL-C and ApoB reductions was projected for 50 mg vs. 25 mg dose, which are both superior to 10 mg.Conclusion: The results support selecting 25 mg Q3M dose for a future Phase 3 trial to ascertain the benefit of plozasiran to reduce major adverse cardiovascular events in patients with established or higher risk of developing atherosclerotic cardiovascular diseases (ASCVD). Dose adjustment is not recommended for patients with different demographic characteristics and comorbidities, or background lipid lowering therapies.Citations: no citation
A Bayesian Model-based CTS Tool to Optimize Clinical Trial Design in Duchenne Muscular Dystrophy
Authors: Xu Qiushuang (Rachel) , Belfiore-Oshan Ramona , Cui Zihan , Zhang Yi , Podichetty Jagdeep
Published: February 2025

Objectives: Duchenne Muscular Dystrophy (DMD) is a rare disease with variable and non-linear progressions. To better understand the relationship between longitudinal disease dynamics and clinically meaningful outcome measures, the Duchenne Regulatory Science Consortium (D-RSC) team has developed Bayesian models of disease progression, dropout models and joint models of longitudinal changes based on velocity endpoints (supine-stand, 4-stair climb, 10-meter/30-foot walk/run), forced vital capacity (FVC) and North Star Ambulatory Assessment (NSAA) from DMD studies. These models were incorporated into a Clinical Trial Simulation (CTS) tool containing the disease progression, the drug effect and the dropout components simulated in silico, to optimize the design of potential future therapies for DMD.Methods: Expanding on our existing DMD CTS tool and previous investigation[1], we incorporated the additional dropout component to the final tool. The tool is implemented in R and containerized into two components: a Shiny web app and a standalone R package, allowing for more flexible usage.Results: We showcase the capability of the updated tool with a case study that will show how this tool is expected to help simulate drug development in DMD and accelerate the path to new therapies. The user can choose the endpoint of interest, proposed inclusion criteria for the trial, proposed length of the trial, and estimated drug effects, and can then perform simulations. Each of the input parameters can be altered until an optimal trial design is determined. This can then be repeated for one or more of the other endpoints of interest. Conclusion: The Bayesian disease progression models used here represent a sophisticated and innovative quantitative methodology for clinical trial simulations. The resulting drug development tool will help inform the selection of optimal trial design parameters for clinical trials of potential therapeutic candidates for DMD.Citations: [1] Lingineni K, Aggarwal V, Morales JF, et al. Development of a Model-based Clinical Trial Simulation Platform to Optimize the Design of Clinical Trials for Duchenne Muscular Dystrophy. CPT Pharmacometrics Syst Pharmacol. Dec 8 2021;doi:10.1002/psp4.12753
A Model-Informed Drug Development Framework for the Development and Dose Optimization of Targeted Radiation Therapies
Authors: Stephens Hunter , Koirala Bhabuk , Apgar Joshua , Watson Kenny , Manon Amandine , Trame Mirjam
Published: February 2025

Objectives: While targeted radiation therapies (TRTs) are raising more and more interest in the oncology space, the regulatory landscape continues to evolve leaving development teams without clear guidance. Model-Informed Drug Development (MIDD) can provide key insights into optimizing doses to achieve maximum efficacy within safety bounds, as well as the design of novel therapeutics with enhanced therapeutic index. The theranostic nature of TRTs allows for precise modelling and prediction of drug kinetics and absorbed doses which will allow for better decision-making in the development process. In this abstract, we present an end-to-end framework for using MIDD with TRTs, specifically with PSMA targeting radio-ligands.Methods: Taking both plasma activity samples and combining with nuclear imaging, the drug kinetics was modelled in both the blood and organs of interest. The semi-mechanistic compartmental models incorporated any saturable uptake of the radio-ligand into peripheral organs of interest as a function of tissue volume and target expression. Parameterizing the models in terms of drug radioactivity allowed for the calculation and prediction of absorbed doses into specific organs of interest. These models were used to optimize drug properties such as binding affinity, and plasma half-life to improve therapeutic index and support candidate selection. Subsequently, at later stages, with the ability to predict organ absorbed dose, the dosing regimen can be optimized by minimizing the simulated adverse event profile linked to specific organs while maximizing tumour exposure. Results: The MIDD framework was validated using published clinical data with published Pluvicto (lutetium Lu 177 vipivotide tetraxetan). The framework made accurate predictions of across a range of doses, PSMA densities, and tumor volumes accounting for distribution and competitive binding of labeled and un-labeled drug in tumor and non-tumor tissues. In addition, the framework allowed to characterize the specific radioactive dose absorbed into blood and various organs such as liver, kidney, spleen, salivary gland and tumor. The absorbed dose predictions were in good alignment with the patient specific dosimetry results. Subsequently, the model predicted exposures were linked to safety and efficacy endpoints which allowed extrapolation from the dosimetry to clinical endpoints.Conclusions: The MIDD framework can be utilized to translate drug design features such as receptor binding affinity on the disposition in various organs of the radio-labeled drug to inform clinical candidate selection to help maximize the therapeutic index. Subsequently, the framework can be utilized to establish first-in-human dosing regimens and to optimize recommended Phase 2 doses.Citations: none
Delineate: a Literature Co-Pilot for Quantitative Systems Pharmacology
Authors: Nieves Emily , Iqbal Jawad , Ullah Ayat , Ornee Tasfia , Sikder Shaon , Mahmud Shahad
Published: February 2025

Objectives: Scientific literature contains a wealth of information and data that can be used to inform QSP models. However manual curation and digitization of literature data is an extremely time intensive process. Large Language Models (LLMs) may improve efficiency of literature tasks, but general purpose LLMs such as GPT-4 or Claude-3 fall short in their ability to handle the technical complexities of the QSP domain. General models often hallucinate responses and rely on the information in their training data which may be inaccurate. Our aim in constructing Delineate is to leverage advanced LLM approaches to rapidly mine and structure data from scientific literature, enabling accurate and accelerated QSP modeling. Methods: To tailor best-in-class LLMs for systems pharmacology applications, we designed an agent-based architecture capable of partitioning complex tasks into modular subtasks. This partitioning approach has been shown to increase robustness by allowing the system to focus on smaller, more manageable components, reducing the likelihood of errors and enabling optimization of each subtask [1]. We evaluated our agent system on a benchmark set comprising diverse tasks such as replicating components of models from literature, performing advanced Q&A on published models, and obtaining parameter values from experimental papers. Since the majority of literature data is found encoded in plots, we designed computer vision algorithms that when combined with our LLM agents provide a semi-automated plot digitization solution. Certain tasks of plot digitization such as axis and label detection, and point identification are automated. The context around how the data was collected, such as trial design and dosing schedules, are also extracted via LLM and restructured into a tabular, user-defined format along with the digitized data. We compared the accuracy and speed of Delineate’s semi-automated plot digitizer to that of the commonly used Web Plot Digitizer [2].Results: The Delineate platform allows for 70% faster digitization of plots compared to Web Plot Digitizer. In addition, the Delineate platform is able to autofill user-defined fields related to the plot such as experimental and clinical conditions under which the data was collected with 92% accuracy on a testing set of 100 clinical trial papers. The accuracy of our LLM agent on the QSP-related benchmarking set rose to 95% from 22% with GPT-4. Conclusions: By combining computer vision techniques with LLM agents, Delineate achieves time saving and accuracy gains in literature-based tasks. Delineate may enable the construction of large datasets for parameter fitting and model validation, easier replication of published models, and efficient knowledge consolidation to support QSP model building.Citations: [1] Ruan, J. et al. “TPTU: Large Language Model-based AI Agents for Task Planning and Tool Usage,” 2023[2] Rohatgi, A. "Webplotdigitizer,” 2022
A Neuro-Dynamic Quantitative Systems Pharmacology (QSP) Model to Describe Pathophysiology of Alzheimer’s Disease and Inform Drug Development
Authors: Cao Youfang , Willis Brian , Sachdev Pallavi , Penner Natasha , Wildsmith Kristin , Charil Arnaud , Horie Kanta , Koyama Akihiko , Reyderman Larisa
Published: February 2025

Objectives: Lecanemab is an anti-amyloid monoclonal antibody and was approved as a disease-modifying treatment with demonstrated significant clinical benefit in slowing cognitive decline in early Alzheimer's disease (AD). Lecanemab selectively binds soluble amyloid-β (Aβ) protofibrils, which is the neurotoxic amyloid species that modulates tau pathology. A neuro-dynamic QSP model was developed to provide a computational framework that integrates data on lecanemab mechanism of action with disease biology.Methods: The QSP model incorporated 3 interlinked modules: Aβ pathway, tau pathway, and cognitive decline, where Aβ triggers tau pathology leading to cognitive decline due to neurodegeneration. Mechanisms within each module and their interlinks were informed by literature evidence, preclinical and clinical data. The model was developed using nonlinear mixed-effect modeling of a multidimensional dataset (Nf4056) consisting of cognitive scores (CDR-SB and ADAS-Cog), imaging (amyloid and tau PET), and biomarker (plasma Aβ42/40 ratio and tau phosphorylated at residue 181 [p-tau181]) data from lecanemab Phase 2 and Phase 3 trials, as well as amyloid PET, CDR-SB and ADAS-Cog data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The model was validated with data from other anti-amyloid antibodies (aducanumab and gantenerumab). Simulations were conducted to investigate long-term lecanemab benefits of monthly (Q4W) maintenance dosing (MD) following initial biweekly (Q2W) treatment.Results: The final QSP model has 11 differential equations and 74 parameters, which were estimated with reasonable precisions (RSE≤30%). The model describes amyloid pathway as an aggregation cascade from monomers to oligomers, protofibrils, and plaques, and the tau pathway as a multi-staged progression of AD pathology with different levels of misfolded tau aggregates leading to formation of neurofibrillary tangles (NFT). High NFT neurons spread tau seeds, which drive tau pathology cycle. The QSP model was able to describe the pathological progression of imaging and plasma biomarkers and cognitive scores during 3 decades of AD progression. Simulations showed that lecanemab Q4W MD following the 18-month Q2W treatment continues to reduce Aβ protofibrils and plaques inhibit progression of amyloid and tau pathologies, as measured by plasma p-tau181 and Aβ42/40 ratio, suppress tau PET, and slow cognitive decline.Conclusions: A neuro-dynamic QSP model was developed based on clinical data as a modeling framework for AD pathophysiology and clinical outcomes. QSP simulations demonstrated benefits of continuing lecanemab treatment after plaque removal and support Q4W MD following initial Q2W treatment.Citations: none
Branchless Banking Services and Financial Stability of Commercial Banks in Kenya
Authors: Momanyi Moraa Lucy , Mungai Dr. John
Published: February 2025

Purpose: Financial stability is a key goal for commercial banks, as it allows them to operate effectively in fulfilling their role as intermediaries in the financial system. Technological advancements, creative financial products, shifting consumer needs, and the utilization of different distribution channels are all having an impact on the banking sector. The purpose of this study was to investigate how Kenyan commercial banks' financial stability is impacted by branchless banking services.
Methods: Using an explanatory research approach, the study concentrated on all 38 commercial banks as of December 31, 2023. From commercial banks, primary and secondary data spanning the years 2016 to 2022 was gathered. Data collecting sheets were used to gather secondary data. The gathered data were coded, cleaned, tabulated, and shown in tables before analysis. Statistics, both descriptive and inferential, were used to conclude. Descriptive statistics included the mean and standard deviation and inferential statistics included regression analysis. STATA 15 software was used for the analysis in this study.
Results: The study found a positive and significant relationship between agency, mobile, and online banking services and financial stability.
Conclusion: Agency, mobile, and online banking services have a positive and significant effect on financial stability of commercial banks. The study made recommendations that commercial banks should implement measures that will lead to increased use of branchless services such as ATM banking, agency banking, mobile banking, and online banking to improve their financial stability. The study also recommended that policymakers should make policies that aim at increasing the use of branchless banking services.
Hubungan Tingkat Pengetahuan Dengan Sikap Remaja Terhadap Infeksi Menular Seksual Pada Siswa Di SMAN 7 Makassar
Authors: Salsabila Husna Farhana , Salina
Published: February 2025

Latar Belakang: Infeksi menular seksual (IMS) merupakan salah satu jenis penyakit infeksi yang penularannya melalui hubungan seksual. Penularan IMS juga ditularkan melalui hubungan seks dengan berganti-ganti pasangan yang sudah tertular. IMS merupakan masalah kesehatan global dengan 1 juta kasus harian, 151 juta di Asia, 11.133 di Indonesia, dan 121 di Sulawesi Selatan. Tujuan: penelitian ini bertujuan untuk mengetahui hubungan tingkat pengetahuan dengan sikap remaja terhadap infeksi menular seksual pada siswa SMAN 7 Makassar. Metode: penelitian ini menggunakan desain penelitian deskriptif analisis dengan pendekatan cross sectional study (data dikumpulakan pada saat waktu tertentu). Teknik pengambilan sampel menggunakan simple random sampling (Pengambilan sampel secara acak dan sederhana) sebanyak 91 responden siswa kelas X-XII di SMAN 7 Makassar, dan data didistribusikan menggunakan Kuesioner berupa angket. Hasil: Tingkat pengetahuan tentang IMS dan sikap terhadap IMS pada responden sebagian besar dalam kategori baik, dengan 74,7% memiliki pengetahuan baik dan 71,4% memiliki sikap baik. Terdapat hubungan signifikan antara tingkat pengetahuan dengan sikap remaja terhadap IMS pada siswa SMAN 7 Makassar yang dibuktikan dengan Uji Chi-square dengan nilai p value 0,000 (p < 0.05). Kesimpulan: Terdapat hubungan yang signifikan antara tingkat pengetahuan dengan sikap remaja terhadap infeksi menular seksual pada siswa di SMAN 7 Makassar.
From gear to culture: How technology shapes the world of rock climbing
Authors: Suputra Gusti Ketut Alit , Aprianoto Aprianoto , Wajdi Majid , Sekarti Ni Ketut
Published: February 2025

Rock climbing is a form of mountaineering that involves navigating steep cliffs, making it a physically demanding and extreme sport. Introduced in Indonesia in the 1970s, it has evolved from local expeditions to international competitions, gaining popularity among youth and adventure seekers. The sport requires both physical prowess and mental agility, blending strength, strategy, and safety. This paper explores the fundamental aspects of rock climbing, focusing on climbing techniques, necessary equipment, and the importance of safety. The objectives are to provide a comprehensive understanding of the sport, highlight its physical and mental benefits, and promote it as a fulfilling and educational activity. These benefits include enhanced physical strength, improved coordination, cognitive skill development, and boosted self-confidence. Data collection involved field observations of rock climbing environments and routes to capture the technical challenges and strategies used by climbers. Interviews with experienced climbers provided valuable insights into their experiences, techniques, and psychological approaches to overcoming obstacles. These qualitative methods allowed for a deeper understanding of the sport's physical, emotional, and technical dimensions. The analysis of the data highlights the sport’s rising international recognition, including its presence in the Olympics. It also underscores the cultural significance of rock climbing in Indonesia and the strategic role it plays in physical and mental development. This paper concludes by advocating for the growth of rock climbing as a popular and enriching sport, with the potential to positively influence personal development.
The advocacy blueprint: A Delphi study on promoting and strengthening mental health programs and services in higher education
Authors: Taja-on Evan P. , Vergara Fremativo A.
Published: February 2025

Academic institutions’ mental health programs and services play a vital role in nurturing students’ well-being and success. Despite progress, challenges in implementation and the need for sustainable strategies highlight the importance of collaborative efforts to optimize mental health programs and create supportive academic environments. This research is important as it bridges gaps in existing knowledge and lays a foundation for both future academic inquiry and practical application. The study engaged experienced mental health advocates and professionals through a two-round Delphi process to refine strategies for improving mental health programs in academic institutions. The exploratory stage identified twenty-one essential strategies for developing sustainable and inclusive mental health programs in academic settings, emphasizing the importance of policy integration, culturally responsive interventions, peer support networks, technology utilization, capacity building, and resource advocacy. The integration stage further synthesized these into nine strategies, highlighting the need for embedding mental health into institutional policies, strengthening leadership accountability, fostering community collaboration, enhancing program accessibility, and promoting awareness through education and innovation. The findings underscore the value of evidence-based practices, professional development, and regular evaluation mechanisms to ensure adaptability, inclusivity, and long-term program sustainability, offering critical implications for practice, policy, and future research.
Sulayman Al Bassam, un poète dans la Cité
Authors: Bassil Rita , Al Bassam Sulayman
Published: February 2025

Cet article retrace le parcours dramaturgique de l’auteur et artiste anglo-koweïtien Sulayman Al Bassam, dont l’oeuvre est habitée par un Levant en prise avec la tourmente ayant suivi les accords Sykes-Picot. Sa deuxième compagnie, SABAB Theatre, fondée après les attentats du 11 septembre 2001, est engagée dans un long processus critique, à la fois endogène et exogène, ayant débuté par la création d’une première trilogie shakespearienne sous un prisme arabe. L’orientalisme et le colonialisme des puissances occidentales occupent, dans son travail, une place aussi importante que la censure, la dictature et le patriarcat dans les sociétés arabes. Son travail dialogue en permanence avec l’actualité régionale et internationale.
Who am I really? Contemporary Narratives of Migration as an Inspiration for Self-discovery
Authors: Zając Justyna , Michułka Dorota
Published: February 2025

Abstract
The aim of this article is to present the results of a study of children's reception of Sarah Crossan's novel The Weight of Water ([2012] 2019). The book shows the process of emotional and social maturation of a girl coming from a Polish family affected by the experience of migration. Letters written by primary school pupils to Kasia, the fictional protagonist, bravely struggling with family problems and peer bullying, were analysed. The cognitive science research we carried out on the reception of literature shows that Crossan's novel serves the self-discovery of the audience, but it also exposes the image of a transnational family, and shows the broader social context of considering the migratory cultural adaptation of a teenage girl. Thus, the case of Kasienka becomes an "element" of building the image of contemporary migrant identity.
 
ResumenEl objetivo de este artículo es presentar los resultados de un estudio sobre la recepción de la novela The Weight of Water ([2012] 2019) de Sarah Crossan por parte de niños y niñas. El libro retrata el proceso de maduración emocional y social de una niña de una familia polaca afectada por la experiencia de la migración. Se analizaron cartas escritas por alumnos de primaria dirigidas a Kasia, la protagonista ficticia, que lucha valientemente contra problemas familiares y el acoso por parte de sus compañeros. La investigación en ciencias cognitivas sobre la recepción de la literatura que hemos realizado muestra que la novela de Crossan favorece el autodescubrimiento de los lectores, al tiempo que expone la imagen de una familia transnacional y reflexiona sobre el contexto social más amplio de la adaptación cultural migratoria de una adolescente. Así, el caso de Kasienka se convierte en un "elemento" en la construcción de la identidad migrante contemporánea.
 
Resum 
L'objectiu d'aquest article és presentar els resultats d’un estudi sobre la recepció de la novel·la The Weight of Water ([2012] 2019) de Sarah Crossan per part dels infants. El llibre retrata el procés de maduració emocional i social d’una jove d’una família polonesa afectada per l’experiència de la migració. Es van analitzar cartes escrites per alumnes de primària adreçades a Kasia, la protagonista fictícia, que lluita amb valentia contra problemes familiars i assetjament per part dels seus companys. La investigació en ciències cognitives sobre la recepció de la literatura que hem realitzat mostra que la novel·la de Crossan afavoreix l’autodescobriment dels lectors, alhora que exposa la imatge d’una família transnacional i reflexiona sobre el context social més ampli d’adaptació cultural migratòria d’una adolescent. Així, el cas de Kasienka esdevé un "element" en la construcció de la identitat migrant contemporània.
Editorial: Critical Pedagogy in Literary Education: Reading the Word to read the World
Authors: Mínguez-López Xavier , Kalogirou Tzina
Published: February 2025

The current special issue of JLE embodies Freire’s goal of literacy/literary education: reading the word to read the world.  The cornerstone of Critical Pedagogy lies undoubtedly in Paulo Freire’s seminal work, Pedagogy of the Oppressed. (Pedagogia do Oprimido, 1968). Freire critiques traditional education models, which he terms the "banking model," in which teachers deposit knowledge into passive students. He advocates for a dialogic approach that transforms education into a collaborative process of inquiry. Freire’s methods emphasize critical consciousness (conscientização), urging learners to question societal structures and their own roles within them. Aiming to empower minds through dialogue and reflection, Critical Pedagogy sees literature as more than an artistic endeavor; it is a medium through which societies interrogate their values, challenge injustices, and envision alternate realities. In the realm of education, how literature is taught can either reinforce systems of oppression or act as a transformative tool for liberation. Critical Pedagogy provides a compelling framework for rethinking literary education. This approach not only democratizes the classroom but also empowers students to become agents of social change.
Tiempo escolar y familias monoparentales: desvelando una experiencia invisibilizada
Authors: Carrasco Tenorio Lidia
Published: February 2025

En este artículo se profundiza sobre cómo las familias monomarentales, familias con una mujer al frente, integran en su rutina diaria el proceso y acompañamiento educativo de sus hijas e hijos. Para ello, se han analizado las entrevistas de 34 mujeres de Zaragoza, madres de familias monomarentales con menores en las etapas de infantil, primaria y secundaria, en las que se preguntaba sobre el tipo de jornada, servicios utilizados, tareas y refuerzos escolares, tutorías, así como por su implicación y participación en la comunidad educativa. Aunque se constata que las familias monomarentales logran compatibilizar la vida laboral y familiar con los tiempos escolares, esto no se consigue sin sacrificios o pérdidas.  Así, el esfuerzo dedicado por ellas es mayor que el invertido por las personas adultas al frente de familias biparentales. Por otra parte, el tiempo de permanencia de sus hijas e hijos en el centro educativo es notablemente largo, ya que en muchos casos a las horas lectivas se les suma el tiempo de comedor, extraescolares y, en menor medida, madrugadores. Asimismo, se hace patente que la comunicación desde el sistema educativo no tiene en cuenta la realidad de las familias monomarentales. Aunque el éxito académico de los menores a cargo de estas familias se ve condicionado tanto desde el punto de vista socioeconómico como desde la comunicación escuela-familia, las madres monomarentales suplen de manera resiliente estas desventajas. Urge que el sistema educativo y los tiempos escolares se organicen teniendo en cuenta a las familias monomarentales.
The interpretation of V. Bryusov's novellas by Chinese critics
Authors: Hu Yingnan
Published: February 2025

The article is devoted to the interpretation of V. Bryusov's novellas by Chinese critics and the identification of factors influencing their perspectives. The focus of the research is the works of Chinese literary scholars studying V. Bryusov's novellas. The analysis reveals that the initial introduction of V. Bryusov's novellas in China began in the 1920s, influenced by the "May Fourth Movement." However, from the mid-1930s to the late 1980s, the study of V. Bryusov's novellas in China did not progress. Since the early 1990s, Chinese critics have once again turned their attention to V. Bryusov's works, leading to the emergence of numerous new research directions. In light of this, the study of the reception of V. Bryusov's novellas in China is typically divided into two periods: early criticism (1920s–1940s) and contemporary criticism (1990s–present). The aim of this work is to provide a comprehensive overview of the Chinese reception of V. Bryusov's short prose, taking into account changes in the socio-political environment. To achieve this goal, the following research methods are employed: cultural-historical and comparative analysis. The study of V. Bryusov's works in China during different periods exhibited distinct characteristics. In the early stage of reception, Chinese literary criticism was heavily influenced by political and social factors, which was reflected in the critical evaluation of his works. Contemporary Chinese researchers studying V. Bryusov's novellas primarily focus on the poetic principles of symbolism and the dystopian themes in his works. In recent years, new research directions have emerged, such as the analysis of disaster depictions, female consciousness in V. Bryusov's works, and comparative studies. The scientific novelty of this work lies in identifying the Chinese-specific reception of V. Bryusov's literary works based on an analysis of critical and literary studies in Chinese.
The conserved ATPase PCH-2 controls the number and distribution of crossovers by antagonizing their formation in Caenorhabditis elegans
Authors: Patel Bhumil , Grobler Maryke , Herrera Alberto , Logari Elias , Ortiz Valery , Bhalla Needhi
Published: February 2025

Meiotic crossover recombination is essential for both accurate chromosome segregation and the generation of new haplotypes for natural selection to act upon. This requirement is known as crossover assurance and is one example of crossover control. While the conserved role of the ATPase, PCH-2, during meiotic prophase has been enigmatic, a universal phenotype when pch-2 or its orthologs are mutated is a change in the number and distribution of meiotic crossovers. Here, we show that PCH-2 controls the number and distribution of crossovers by antagonizing their formation. This antagonism produces different effects at different stages of meiotic prophase: early in meiotic prophase, PCH-2 prevents double-strand breaks from becoming crossover-eligible intermediates, limiting crossover formation at sites of initial double-strand break formation and homolog interactions. Later in meiotic prophase, PCH-2 winnows the number of crossover-eligible intermediates, contributing to the designation of crossovers and ultimately, crossover assurance. We also demonstrate that PCH-2 accomplishes this regulation through the meiotic HORMAD, HIM-3. Our data strongly support a model in which PCH-2’s conserved role is to remodel meiotic HORMADs throughout meiotic prophase to destabilize crossover-eligible precursors and coordinate meiotic recombination with synapsis, ensuring the progressive implementation of meiotic recombination and explaining its function in the pachytene checkpoint and crossover control.
Visual homogeneity computations in the brain enable solving property-based visual tasks
Authors: Jacob Georgin , Pramod RT , Arun SP
Published: February 2025

Most visual tasks involve looking for specific object features. But we also often perform property-based tasks where we look for specific property in an image, such as finding an odd item, deciding if two items are same, or if an object has symmetry. How do we solve such tasks? These tasks do not fit into standard models of decision making because their underlying feature space and decision process is unclear. Using well-known principles governing multiple object representations, we show that displays with repeating elements can be distinguished from heterogeneous displays using a property we define as visual homogeneity. In behavior, visual homogeneity predicted response times on visual search, same-different and symmetry tasks. Brain imaging during visual search and symmetry tasks revealed that visual homogeneity was localized to a region in the object-selective cortex. Thus, property-based visual tasks are solved in a localized region in the brain by computing visual homogeneity.
Multiplexed assays of human disease-relevant mutations reveal UTR dinucleotide composition as a major determinant of RNA stability
Authors: Su Jia-Ying , Wang Yun-Lin , Hsieh Yu-Tung , Chang Yu-Chi , Yang Cheng-Han , Kang YoonSoon , Huang Yen-Tsung , Lin Chien-Ling
Published: February 2025

Untranslated regions (UTRs) contain crucial regulatory elements for RNA stability, translation and localization, so their integrity is indispensable for gene expression. Approximately 3.7% of genetic variants associated with diseases occur in UTRs, yet a comprehensive understanding of UTR variant functions remains limited due to inefficient experimental and computational assessment methods. To systematically evaluate the effects of UTR variants on RNA stability, we established a massively parallel reporter assay on 6555 UTR variants reported in human disease databases. We examined the RNA degradation patterns mediated by the UTR library in two cell lines, and then applied LASSO regression to model the influential regulators of RNA stability. We found that UA dinucleotides and UA-rich motifs are the most prominent destabilizing element. Gain of UA dinucleotide outlined mutant UTRs with reduced stability. Studies on endogenous transcripts indicate that high UA-dinucleotide ratios in UTRs promote RNA degradation. Conversely, elevated GC content and protein binding on UA dinucleotides protect high-UA RNA from degradation. Further analysis reveals polarized roles of UA-dinucleotide-binding proteins in RNA protection and degradation. Furthermore, the UA-dinucleotide ratio of both UTRs is a common characteristic of genes in innate immune response pathways, implying a coordinated stability regulation through UTRs at the transcriptomic level. We also demonstrate that stability-altering UTRs are associated with changes in biobank-based health indices, underscoring the importance of precise UTR regulation for wellness. Our study highlights the importance of RNA stability regulation through UTR primary sequences, paving the way for further exploration of their implications in gene networks and precision medicine.
Stock market trading via actor-critic reinforcement learning and adaptable data structure
Authors: Guevara Cesar
Published: February 2025

Currently, the stock market is attractive, and it is challenging to develop an efficient investment model with high accuracy due to changes in the values of the shares for political, economic, and social reasons. This article presents an innovative proposal for a short-term, automatic investment model to reduce capital loss during trading, applying a reinforcement learning (RL) model. On the other hand, we propose an adaptable data window structure to enhance the learning and accuracy of investment agents in three foreign exchange markets: crude oil, gold, and the Euro. In addition, the RL model employs an actor-critic neural network with rectified linear unit (ReLU) neurons to generate specialized investment agents, enabling more efficient trading, minimizing investment losses across different time periods, and reducing the model’s learning time. The proposed RL model obtained a reduction average loss of 0.03% in Euro, 0.25% in gold, and 0.13% in crude oil in the test phase with varying initial conditions.
Optimizing power allocation for URLLC-D2D in 5G networks with Rician fading channel
Authors: Muhammad Owais , Jiang Hong , Bilal Muhammad , Muhammad Umer Mushtaq
Published: February 2025

The rapid evolution of wireless technologies within the 5G network brings significant challenges in managing the increased connectivity and traffic of mobile devices. This enhanced connectivity brings challenges for base stations, which must handle increased traffic and efficiently serve a growing number of mobile devices. One of the key solutions to address these challenges is integrating device-to-device (D2D) communication with ultra-reliable and low-latency communication (URLLC). This study examines the impact of the Rician fading channel on the performance of D2D communication under URLLC. It addresses the critical problem of optimizing power allocation to maximize the minimum data rate in D2D communication. A significant challenge arises due to interference issues, as the problem of maximizing the minimum data rate is non-convex, which leads to high computational complexity. This complexity makes it difficult to derive optimal solutions efficiently. To address this challenge, we introduce an algorithm that is based on derivatives to find the optimal power allocation. Comparisons are made with the branch and bound (B&B) algorithm, heuristic algorithm, and particle swarm optimization (PSO) algorithm. Our proposed algorithm improves power allocation performance and also achieves faster execution with lower computational complexity compared to the B&B, PSO, and heuristic algorithms.
Biocatalysis - new fundamental knowledge and technologies
Authors: Varfolomeev Sergey
Published: February 2025

In 2024, the 50th anniversary of the organization of the Department of Chemical Enzymology at the Faculty of Chemistry of Lomonosov Moscow State University is celebrated. The organization and active development of the department ensured the formation of an entire field of knowledge, the implementation of fundamentally new effective technologies. Currently, enzymes are catalysts deeply studied at the molecular level with an understanding of the detailed mechanisms of catalysis, catalysts designed by protein engineering with the creation of new necessary properties. Enzymes are the basis of modern analysis of complex biomolecules and biopolymers, the basis of new methods of medical diagnostics. Enzymes as participants in key physiological processes are the subject and tool of modern molecular medicine, the basis of many processes of fine organic synthesis and drug production. Research over the past five years demonstrates the key role of enzymes in the functioning of the human central nervous system, in the molecular basis of intelligence. Biohydrogen, biomethane, biodiesel, bioethanol are basic renewable fuel materials, the production of which is based on enzymatic processes. Biotechnological processes of environmental protection use biocatalysis as a tool for destruction of ecotoxicants. Biocatalysis is a component of industrial biotechnology. The Department of Chemical Enzymology has made a significant contribution to the development of these areas in the country and abroad.
Minerals of meteorites and the Earth’s mantle: their response to “Faustian” temperatures and pressures
Authors: Pushcharovsky Dmitry
Published: February 2025

The new high-pressure minerals from meteorites and impact craters can be considered as possible components of the deep-seated Earth’s shells. Obviously they exhibit a definite geophysical interest. The important results of structure studies of high-pressure (HP) minerals, obtained in 20182022, are reviewed. A special attention is addressed to the new structure transformations in Earth’s interior of olivine (asimowite, poirierite), pyroxene (akimotoite, hemleyite) and feldspars (lingunite, liebermanite) related with the crystallization of previously unknown their polymorphic modifications. The intergrowths of poirierite with wadsleyite/ringwoodite in impact chondrites confirm the idea that the transformation of olivine into ringwoodite occurs through formation of poirierite. The structure and composition of new high-pressure minerals from impact regions and meteorites carry information about the complex petrology of deep geospheres, which cannot be manifested in products of laboratory experiments.
The Impact of Design Thinking vs Rote Learning on Secondary Student Achievement: An Experimental Study in Bangkok Schools
Authors: Ekvitayavetchanukul Pongkit , Sutabutra Tanai , Rujachan Phawat , Manasakorn Kasame , Sripetchnai Monchai , Ekvitayavetchanukul Patraporn
Published: February 2025

This study investigates the comparative effectiveness of design thinking versus traditional rote learning approaches among secondary school students in Bangkok, Thailand. Through an experimental research design involving 250 students from grades 10-12, the study examines learning outcomes, engagement levels, and student perceptions of both pedagogical approaches. Data was collected through a comprehensive Google Forms survey instrument, which measured academic performance, creative problem-solving abilities, and student satisfaction.
The findings, analyzed using independent t-tests and ANOVA, indicate that students exposed to design thinking methodologies demonstrated significantly higher levels of engagement (p < 0.001, d = 0.73) and improved problem-solving capabilities compared to those using traditional rote learning methods. Specifically, 73% of students in the design thinking group showed enhanced critical thinking skills, while 68% demonstrated an increased ability to apply knowledge to real-world situations. Furthermore, student satisfaction scores were notably higher in the design thinking approach, with 82% of participants reporting increased motivation and interest in their learning process (t (248) = 4.62, p < 0.001).
These results suggest that implementing design thinking strategies in Thai secondary education could substantially improve student learning outcomes and better prepare students for future academic and professional challenges. The study provides valuable insights for educators and policymakers, supporting evidence-based pedagogical reforms in the Thai educational system and broader Asian educational contexts.
Impact of Varied Compost Rates on Arbuscular Mycorhhiza Fungi in Rhizosphere Soils of Capsicum chinense (Habanero Pepper)
Authors: A. O. Nengi-Benwari, , Oghenerounano Jerusalem, Aaron
Published: February 2025

The population and diversity of soil organisms are important factors in maintaining soil fertility and quality. The aim of this study was to determine the impact of varied compost rates on Arbuscular Mycorrhiza Fungi, rhizosphere soils of Capiscum chinense. Soil samples were treated with various concentrations of compost (0 g, 200 g, 400 g, 600 g. 800 g and 1000 g). Systematic method of random sampling was used to collect soil samples from the rhizosphere of the various soils of different compost rates using a spade and hand trowel at a depth of 0-10cm. Results showed significant difference (P<0.05) in the Arbuscular Mycorrhiza Fungi (AMF) across all compost rates. AMF population ranged from 67 – 100 g/dwt respectively with the highest AMF population observed under 400 g(100 g/dwt, while the lowest AMF population was recorded under 600 g/dwt. Results for microbial diversity showed variation across all compost rates. A total of four AMF species were extracted from the rhizosphere of the soils. Acaulospora spp was the most predominant AMF in the studied soils. Highest microbial diversity was observed under the 1000 g. Conversely, lowest microbial diversity was found under 0 g compost rates. All six compost rates had effect on the AMF population but 1000 g exerted the most effect. These effects could be as a result of compost passive by-product of nutrient uptake, Root structure and soil organisms.
Social Support Interventions for Pandemic Survivors Who Are Resident in Victoria, Australia
Authors: Mandoh Sulaiman L , Bwititi Phillip T , Nwose Ezekiel U
Published: February 2025

Background: The impacts of the 2014-16 Ebola Virus Disease epidemic and the COVID-19 pandemic on West Africans who survived these events were dire and therefore required social support interventions to ease the pain.
Objective: To determine the levels of support which 2014-16 EVD survivors who are resident in Victoria received during the COVID-19 pandemic.
Methods: A sequential exploratory mixed methods research investigated this topic by utilising an online survey which comprised of quantitative questions. Nine interviews were conducted to collect more nuanced data which was analysed using the five stage qualitative data analysis.
Settings: This study was done in Victoria-Australia. Further information could be accessed in the published study protocol (Mandoh et al., 2024).
Result: Most of the 32 participants had 3-5 people to rely on (44%) and most showed interest and concerns a lot during the 2014-16 EVD epidemic (38%). But 56% found it difficult to get help during the 2014-16 EVD epidemic. Similarly, majority had 3-5 people to rely on during the 2019-23 COVID-19 pandemic and were interested and concerned (48%). But it was difficult to get help. Qualitative data showed that unlike during the EVD epidemic, participants received social supports during the COVID-19 pandemic in Australia.
Conclusion: Most of the participants were women whose age range was mainly 18-40 years. Thirty-two individuals participated in the quantitative questions, 9 volunteered to provide qualitative data through the semi structured interview. Despite the interest and concerns, it was difficult to get help.