bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting SARS-CoV-2 main protease: a comprehensive approach using advanced virtual screening, molecular dynamics, and in vitro validation
Authors: Gevorgyan Smbat , Khachatryan Hamlet , Shavina Anastasiya , Gharaghani Sajjad , Zakaryan Hovakim 
Published: December 2024

AbstractThe COVID-19 pandemic, driven by the SARS-CoV-2 virus, necessitates the development of effective therapeutics. The main protease of the virus, Mpro, is a key target due to its crucial role in viral replication. Our study presents a novel approach combining ligand-based pharmacophore modeling with structure-based advanced virtual screening to identify potential inhibitors of Mpro. We screened around 200 million compounds using this integrated methodology, resulting in a shortlist of promising compounds. These were further scrutinized through molecular dynamics simulations, revealing their interaction dynamics with Mpro. Subsequent in vitro assays using the Mpro enzyme identified two compounds exhibiting significant micromolar inhibitory activity. These findings provide valuable scaffolds for the development of advanced therapeutics targeting Mpro. The comprehensive nature of our approach, spanning computational predictions to experimental validations, offers a robust pathway for rapid and efficient identification of potential drug candidates against COVID-19.
Minimal encephalopathy in hereditary hemorrhagic telangiectasia patients with portosystemic vascular malformations
Authors: Villanueva B. , Cañabate A. , Torres-Iglesias R. , Cerdà P. , Gamundí E. , Ordi Q. , Alba E. , Sanz-Astier L. A. , Iriarte A. , Ribas J. , Castellote J. , Pintó X. , Riera-Mestre A. 
Published: December 2024

Abstract
Background
Hereditary hemorrhagic telangiectasia (HHT) is characterized by telangiectasia and larger vascular malformations. Liver malformations are the most frequent visceral involvement including the presence of portosystemic malformations (PSM) that can cause hepatic encephalopathy. Minimal hepatic encephalopathy (mHE) is characterized by alterations of brain function in neuropsychological or neurophysiological tests and decreases quality of life. The evidence of mHE in HHT patients is scarce. The aim of this study is to assess the prevalence and health impact of mHE in patients with and without PSM.

Methods
We performed a cross-sectional observational study in a cohort of patients from an HHT referral unit. Adult patients with definite HHT and PSM and age and sex matched HHT controls without PSM (1:1) were included. Baseline clinical, imaging and laboratory tests and different neuropsychological tests for the screening of mHE were compared between both groups.

Results
Eighteen patients with PSM and 18 controls out of 430 HHT patients were included. Patients with PSM showed higher prevalence of attention disturbances (50% vs. 11.1%, p = 0.027), falls during last 12 months (22.2% vs. 5.6%, p = 0.338), sleep disorders (50% vs. 16.7%, p = 0.075) and a worst performance in s-ANT1 test (14 vs. 19.5 points score, p = 0.739) than HHT controls.

Conclusions
HHT patients with PSM showed higher attention difficulties than HHT controls, though both PSM and HHT controls showed findings of mHE. Specific neuropsychological tests for early detection of mHE should be considered in HHT patients.
Clinical efficacy of efgartigimod combined with intravenous methylprednisolone in the acute phase of neuromyelitis optica spectrum disorders
Authors: Yang Wenjing , Chen Pei , Guo Jiaxuan , Feng Huiyu , Huang Xin 
Published: December 2024

Abstract
Background
Neuromyelitis Optica Spectrum Disorders (NMOSD) comprise a group of autoimmune-mediated, inflammatory, demyelinating central nervous system diseases caused by aquaporin-4 (AQP4) IgG autoantibodies. Efgartigimod is a human IgG Fc fragment that reduces antibody titers by targeting the neonatal Fc receptor (FcRn). This study documents the efficacy of efgartigimod combined with intravenous methylprednisolone (IVMP) in the acute phase of NMOSD.

Methods
In this retrospective study, the medical records of NMOSD patients with acute attack who received efgartigimod plus IVMP or IVMP were reviewed. Treatment efficacy was assessed by the Expanded Disability Scale Score (EDSS) before and one month after treatment. Any side effects that occurred during the treatment period were recorded.

Results
This study was performed on 11 patients (efgartigimod plus IVMP group [n = 4] and IVMP group [n = 7]). Efgartigimod plus IVMP was effective and had a satisfactory safety profile. EDSS was reduced by 0.5 ± 0.32 compared with the IVMP group (0.27 ± 0.02). Immunoglobulin was decreased in three patients, and the immunoglobulin G (IgG) levels gradually increased approximately 8 weeks after the last administration. Hyperlipidemia and elevated white blood cell count were common side effects. No infections or deaths occurred.

Conclusions
Efgartigimod plus IVMP treatment is safe and well-tolerated in patients with acute-phase NMOSD.
International workshop: what is needed to ensure outcome measures for Rett syndrome are fit-for-purpose for clinical trials? June 7, 2023, Nashville, USA
Authors: Downs Jenny , Pichard Dominique C. , Kaufmann Walter E. , Horrigan Joseph P. , Raspa Melissa , Townend Gillian , Marsh Eric D. , Leonard Helen , Motil Kathleen , Dietz Andrew C. , Garg Nupur , Ananth Amitha , Byiers Breanne , Peters Sarika , Beatty Christopher , Symons Frank , Jacobs Aleksandra , Youakim James , Suter Bernhard , Santosh Paramola , Neul Jeffrey L. , Benke Tim A. 
Published: December 2024

Abstract
Introduction
The clinical, research and advocacy communities for Rett syndrome are striving to achieve clinical trial readiness, including having fit-for-purpose clinical outcome assessments. This study aimed to (1) describe psychometric properties of clinical outcome assessment for Rett syndrome and (2) identify what is needed to ensure that fit-for-purpose clinical outcome assessments are available for clinical trials.

Methods
Clinical outcome assessments for the top 10 priority domains identified in the Voice of the Patient Report for Rett syndrome were compiled and available psychometric data were extracted. The clinical outcome assessments measured clinical severity, functional abilities, comorbidities and quality of life, and electrophysiological biomarkers. An international and multidisciplinary panel of 29 experts with clinical, research, psychometric, biostatistical, industry and lived experience was identified through International Rett Syndrome Foundation networks, to discuss validation of the clinical outcome assessments, gaps and next steps, during a workshop and in a follow-up questionnaire. The identified gaps and limitations were coded using inductive content analysis.

Results
Variable validation profiles across 26 clinical outcome assessments of clinical severity, functional abilities, and comorbidities were discussed. Reliability, validity, and responsiveness profiles were mostly incomplete; there were limited content validation data, particularly parent-informed relevance, comprehensiveness and comprehensibility of items; and no data on meaningful change or cross-cultural validity. The panel identified needs for standardised administration protocols and systematic validation programmes.

Conclusion
A pipeline of collaborative clinical outcome assessment development and validation research in Rett syndrome can now be designed, aiming to have fit-for-purpose measures that can evaluate meaningful change, to serve future clinical trials and clinical practice.
SIRT6 deficiency impairs the deacetylation and ubiquitination of UHRF1 to strengthen glycolysis and lactate secretion in bladder cancer
Authors: Wang Xiaojing , Zhang Peipei , Yan Jiaqi , Huang Jingyi , Shen Yan , He Hongchao , Dou Hongjing 
Published: December 2024

Abstract
Background
Aberrant interplay between epigenetic reprogramming and metabolic rewiring events contributes to bladder cancer progression and metastasis. How the deacetylase Sirtuin-6 (SIRT6) regulates glycolysis and lactate secretion in bladder cancer remains poorly defined. We thus aimed to study the biological functions of SIRT6 in bladder cancer.

Methods
Bioinformatic analysis was used to study the prognostic significance of SIRT6/UHRF1 in BLCA. Both in vitro and in vivo assays were used to determine the roles of SIRT6/UHRF1 in BLCA. Deacetylation and ubiquitin assays were performed to uncover the regulations of SIRT6-UHRF1. Measurement of extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) was used to assess glycolytic abilities.

Results
Here, we show that protein deacetylase SIRT6 was down-regulated in BLCA, and predicts poor overall survival. SIRT6 deficiency notably enhances BLCA cell proliferation, self-renewal, and migration capacities in vitro and in vivo. Mechanistically, SIRT6 interacts with, deacetylates, and promotes UHRF1 degradation mediated by β-TrCP1. Thus, SIRT6 deficiency leads to stabilized UHRF1 and depends on UHRF1 to accelerate BLCA malignant progression. Furthermore, UHRF1 significantly increased aerobic glycolysis via activating MCT4/HK2 expressions. Down-regulated SIRT6 thus depended on UHRF1 to promote glycolysis and lactate secretion in BLCA. Targeting UHRF1 or MCT4 notably impaired the extracellular lactate accumulations in BLCA. Significantly, a specific small-molecule inhibitor (NSC232003) targeting UHRF1 substantially inhibited SIRT6-deficient BLCA progression.

Conclusion
Together, our study uncovered an epigenetic mechanism of the SIRT6/UHRF1 axis in driving BLCA glycolysis and lactate secretion, creating a novel vulnerability for BLCA treatment.
Business models and strategies for the internalization of externalities in agri-food value chains
Authors: Mehrabi Sepide , Giagnocavo Cynthia 
Published: December 2024

AbstractCurrent food systems have significant negative environmental, social, and economic impacts. Externalized costs and benefits create false market incentives favoring less healthy and unsustainable options. Transitioning to sustainable agri-food systems requires that businesses internalize these externalities. Internalization of externalities (IOE) is often addressed through policy measures and regulatory initiatives. However, IOE can also be carried out through business models (BMs) and strategies which involve creating positive externalities, mitigating/preventing negative ones, as well as ensuring fair distribution of risks, costs, and benefits. Accordingly, sustainable and innovative BMs and strategies offer pathways to achieving IOE. This paper identifies existing sustainable and innovative BMs and strategies and explains how they can achieve IOE. Using an integrative literature review methodology, we reconcile both economics and business literature approaches. We subsequently carry out two levels of analysis including abductive coding and interrelationship evaluation. The paper explores the characteristics of BMs and strategies that address IOE, using the well-known concept of value and introduces a conceptual framework for categorizing business models and strategies for the internalization of externalities (BM4IOE). The article initiates a discourse on the role of BMs in the IOE within agri-food value chains and provides insights into how businesses can develop and implement models that effectively internalize externalities, thereby enhancing sustainability and driving innovation in the transition of agri-food systems.
Towards a real-time simulation of elastoplastic deformation using multi-task neural networks
Authors: Schmeitz R. , Remmers J. J. C. , Mula O. , van der Sluis O. 
Published: December 2024

AbstractThis study introduces a surrogate modeling framework merging proper orthogonal decomposition, long short-term memory networks, and multi-task learning, to accurately predict elastoplastic deformations in real-time. Superior to single-task neural networks, this approach achieves a mean absolute error below 0.40% across various state variables, with the multi-task model showing enhanced generalization by mitigating overfitting through shared layers. Moreover, in our use cases, a pre-trained multi-task model can effectively train additional variables with as few as 20 samples, demonstrating its deep understanding of complex scenarios. This is notably efficient compared to single-task models, which typically require around 100 samples. Significantly faster than traditional finite element analysis, our model accelerates computations by approximately a million times, making it a substantial advancement for real-time predictive modeling in engineering applications. While it necessitates further testing on more intricate models, this framework shows substantial promise in elevating both efficiency and accuracy in engineering applications, particularly for real-time scenarios.
Preliminary design and evaluation of a ducted-fan type pipeline robot
Authors: Miyake Shota , Yoshida Kento , Sugano Shigeki , Kamezaki Mitsuhiro 
Published: December 2024

AbstractPipelines are crucial infrastructure supporting human life, yet their maintenance costs are substantial, necessitating the development of time-efficient robotic systems. Therefore, this study proposes an in-pipe mobile robot powered by wind generated using a ducted fan rotor, enabling faster movement within pipelines than conventional methods, e.g., inchworm. Deriving the propulsion force from wind requires analyzing airflow within the pipeline, which is challenging due to the confined space and complexity, especially when considering the presence of robots. Hence, we developed a prototype of a ducted-fan type pipeline robot (DPR) and experimentally investigated duct shapes that enhance the propulsion of the DPR within pipelines. As a result, we identified duct shapes that amplify the propulsion force generated by the ducted fan within pipelines. Additionally, we also experimentally elucidated the relationship between the distance from the pipe’s end and the propulsion force of the robot. Furthermore, we demonstrated the capabilities of the DPR by traversing a pipeline with a diameter of 110 mm, achieving speeds of 1500 mm/s in horizontal pipes and 700 mm/s while ascending vertical pipes. The results show that DRP has the potential for in-pipe inspection.
InSAR-based investigation of ground subsidence due to excavation: a case study of Incheon City, South Korea
Authors: Park Kyungwon , Kim Yong Je , Chen Jiannan , Nam Boo Hyun 
Published: December 2024

AbstractGround subsidence is one of geohazards, particularly in urban environment due to its negative impact to nearby buildings and civil infrastructures. This study investigates the amount and spatial distribution of ground subsidence in Incheon City, South Korea, where ground excavation was made. Interferometric Synthetic Aperture Radar (InSAR) was used to monitor surface deformation around the excavation site. The study analyzed subsidence during an excavation project using Sentinel-1b satellite data, and the InSAR results were compared with traditional leveling methods and field measurements. Notable subsidence during the early construction phase was identified, which demonstrates the effectiveness of InSAR in urban environment. The research contributes to understanding of the excavation-inducing ground subsidence due to the reclamation layer.
Impact of integrating type-1 distributed generation on distribution network using modified genetic algorithm and voltage stability index: a technical and cost–benefit analysis approach
Authors: Olabode Olakunle Elijah , Akinyele Daniel Oluwaseun , Ajewole Titus Oluwasuji , Omogoye Samuel Okeolu , Raji Akeem Abimbola 
Published: December 2024

AbstractThe position of the distribution network and its peculiar topology calls for viable means of addressing the issue of severe power loss and voltage instability confronting its ability to truly wheel out the received energy from the transmission arm of the network to the end users. Based on this premise, the current work employed a Lévy flight genetic algorithm (LF-GA) for the placement of type-1 photovoltaic-based distributed generation (PV-DG) into a radial network. The IEEE 33 and Government Residential Area (GRA) 11 kV and 34-bus feeder in Nigeria were used to investigate the effectiveness of the proposed approach. The backward-forward sweep formed the backbone of the load flow, while the voltage stability index was used to select the suitable buses where type-1 DG was integrated for optimal performance. The criteria considered for performance evaluation were the cost of energy loss, payback time, active power loss, and network voltage profile improvement without violating the essential network constraints. The paper proposed a relevant policy framework on DG integration, which filled knowledge gap in the previous studies. A multi-objective factor-based LF-GA subjected to appropriate constraints was used to optimize both the sizing and the locations of type-1 DG with the arrangements implemented in a MATLAB environment. The results obtained when compared with the existing contributions in the literature showed a credible improvement in line-loss reduction, voltage profile, and the system voltage stability index, including reduced cost of energy loss with minimal payback time on the investment of compensating devices.
The impact of a plant-based diet on the menstrual cycle and female fertility
Authors: Grzesik Karina , Pilarczyk Katarzyna , Rabęda Aleksandra , Klepacz Natalia , Cudziło Zuzanna , Sawczuk Hubert , Nowak Weronika Ewa , Kaus Marta , Adamska Hanna , Malicka Marta 
Published: December 2024

Introduction and objective: A plant-based diet is being adopted by an increasing number of people worldwide. Its health benefits have been described in numerous scientific studies. Unfortunately, an improperly balanced diet that excludes animal-derived products can, through various mechanisms, lead to deficiencies and disruptions in the functioning of many systems in the body. This review paper aims to present and summarize the findings and current literature on the impact of a plant-based diet on the menstrual cycle and female fertility.
Brief description of the state of knowledge: There is insufficient research on how minerals and vitamins influence the biochemical processes of the menstrual cycle and related symptoms. While nutrient deficiencies in plant-based diets are widely discussed, most studies focus on general health rather than the reproductive system, which is crucial for hormonal balance and fertility. This highlights the need for more research to improve our understanding of the female reproductive and endocrine systems and ensure better care for women.
Methods: A literature review was conducted using PubMed and Google Scholar with search terms like "impact of plant-based diet", "menstrual cycle disorders", "causes of female infertility", "deficiencies in vegans and vegetarians" and related variations. Articles published within the last five years were prioritized.
Conclusions: A properly followed plant-based diet, supported by supplementation, has a positive effect on the female reproductive system, without causing menstrual cycle disorders or infertility. Unfortunately, the more exclusions present in the diet, the more likely it is to cause deficiencies in minerals and vitamins. Inadequate levels of these nutrients can lead to abnormalities in the female reproductive system, both in laboratory tests and in symptoms experienced by women.
The impact of physical activity on depressive and anxiety disorders: A literature review
Authors: Woźniak Karolina , Woźniak Adam , Stasiak Michał 
Published: December 2024

Purpose of Research:
Depression and anxiety affect over 500 million people globally and are leading causes of disability. While pharmacotherapy and psychotherapy are effective for many, a significant proportion of patients remain resistant. This study examines the role of physical activity as a complementary or alternative treatment for these conditions, focusing on its effects on neuroplasticity, inflammation, and metabolic health.
Research Materials and Methods:
A systematic review of clinical and experimental studies was conducted using PubMed with keywords like “physical activity,” “running,” “mental disorder,” and “depression.” Included studies were assessed for methodology, participant demographics, and therapeutic outcomes.

Basic Results:
Physical activity improves depressive symptoms, neuroplasticity, and metabolic health. Running therapy significantly reduces depressive symptoms and inflammation compared to antidepressants. Preclinical studies show exercise reverses depressive-like behaviors and restores hippocampal function in rodents. Meta-analyses confirm the effectiveness of aerobic and strength exercises as standalone or adjunctive treatments, with variations based on age and gender.
Conclusions:
Physical activity is a cost-effective intervention with significant benefits for mental health, particularly for treatment-resistant patients or those with metabolic comorbidities. Its integration into treatment guidelines could enhance outcomes, emphasizing the need for tailored exercise protocols in future research.
Application of vegetable oils as pharmaceutical ingredient: the impact of liquid lipid type on the characteristics of nanostructured lipid carrier
Authors: Binarjo Annas , Ernidawati  , Khotimah Khusnul , Wahyuningsih Iis , Efiana Nuri Ari 
Published: December 2024

Recently, drug encapsulation using a Nanostructured Lipid Carrier (NLC) has gained attention in formulation studies due to its high loading capacity and prevent drug expulsion during storage. Drug loading capacity is mainly affected by lipid type and composition, especially liquid lipids. Therefore, this research aims to evaluate the potential of avocado oil as a liquid lipid of NLC replacing pure oleic acid. All components including oil, glyceryl monostearate, Tween 20®, and Span 60® were processed to NLC by solvent injection method. The colloidal characteristics of NLC dispersion in water and 20 mM PBS pH 7 were determined, including transmittance, particle size, size distribution, zeta potential, loading capacity (LC), and loading efficiency (LE) of capsanthin in NLC. The results showed that NLC containing oleic acid (Fola) and avocado oil (Favo) dispersion in PBS exhibited a similar transmittance and zeta potential of 69-74% and -51 to -58 mV, respectively, whereas the particle size and size distribution of Favo were significantly higher than Fola. Moreover, the 1.3-fold higher LC and LE of Favo compared to Fola was insignificant (p>0.05). Additionally, the Tween 20® and Span 60® ratio of Favo should be improved to obtain an ideal particle size and size distribution as in Fola. In conclusion, avocado oil indicated the potential to be utilized as a liquid lipid of NLC formulation regarding zeta potential and drug loading. However, the surfactant composition should be adjusted to reduce the particle size of the NLC, leading to permeability enhancement in delivery, particularly oral administration.
O argumento religioso no ensino domiciliar. Uma análise da decisão do Recurso Extraordinário 888.815/RS do Supremo Tribunal Federal
Authors: Ferri Felipe Eduardo Ramos de Oliveira , Estrada Adrian Alvarez 
Published: December 2024

A presente investigação propõe pensar a pauta das famílias a fim de legalizar, no Brasil, a prática do ensino domiciliar, chamado de homeschooling. Dentre os argumentos utilizados, para fundamentar a opção pelo exercício do ensino domiciliar está a liberdade religiosa. Qual a relevância desse argumento? Por meio de análise jurisprudencial, em específico Recurso Extraordinário 888.815/RS, repercussão geral tema 822, apreciado pelo Supremo Tribunal Federal, tal argumento apareceu com frequência nos votos e manifestações das partes e em especifico nos votos dos ministros Luis Roberto Barroso, Alexandre de Moraes e Luiz Fux. A fim de compreender as bases de argumentos e quais desdobramentos decorrem dos mesmos, sejam a favor ou contra o exercício do ensino domiciliar. Os resultados aqui levantados servem de subsídio para pesquisas do tema com viés jurídico ou educacional.