bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Mechanism of Finerenone in Treating Diabetic Nephropathy
Based on Bioinformatics
Authors: Lin Mengshu , Lu Meiqi , Chen Yixuan , Gao Qing 
Published: November 2024

Background:
Diabetic Nephropathy (DN) is the leading cause of the end-stage renal disease
(ESRD). Finerenone (with the molecular formula C21H22N4O3) is an oral non-steroidal mineralocorticoid
antagonist (ns-MRA) that is both highly potent and has strong selectivity for the MR. At
present, it has been used to treat DN. However, the molecular mechanism of finerenone in the treatment
of diabetic nephropathy remains unclear.

Objective:
In this study, we employed bioinformatics approaches to investigate the molecular mechanism
of finerenone as a novel therapeutic agent for the treatment of DN.

Methods:
We examined a number of databases, including GEO, DisGeNET, Genecards, and OMIM,
to find putative genes linked to DN. We then employed the PubChem database and PharmMapper
service platform to identify targets of finerenone. Further analysis was conducted using the DAVID
database for enrichment analysis and the STRING database for protein-protein interaction (PPI) networks.
Molecular docking (MD) was performed using AutoDockTools software, and results were
visualized using PyMOL software.

Results:
In total, we identified 82 drug-disease targets, primarily associated with lipid and atherosclerosis,
diabetic cardiomyopathy, MAPK signaling pathway, and PI3K-Akt signaling pathway. Our
PPI network analysis and docking studies demonstrated good binding ability of finerenone to specific
targets such as AKT1, MMP-9, IGF1, EGFR, CASP3, PPARG, ESR1, MMP-2, and KDR.

Conclusion:
Finerenone has the potential to reduce the progression of DN through various pathways,
including lipid and atherosclerosis, diabetic cardiomyopathy, MAPK signaling pathway, and PI3KAkt
signaling pathway. Moreover, it could exert anti-inflammatory and antifibrotic effects on specific
targets, such as AKT1, MMP-9, IGF1, EGFR, CASP3, PPARG, ESR1, MMP-2, and KDR.
Analysis of Farmers' Entrepreneurial Behavior, and its Effect on Farm Productivity
Authors: Ilham Muh. , Karno Edy , Halim Muliha , Igo BD Abdullah , Hasniah Hasniah , Murniati Murniati 
Published: November 2024

AbstractThis study aims to analyze the entrepreneurial behavior of farmers from the aspect of formal education and farming experience and its influence on farm productivity. The research population was rice paddy farmers in Cialam Jaya Village, Konda Subdistrict, South Konawe District, Southeast Sulawesi Province totaling 215. The number of samples was 140 farmers who were determined proportionally based on the area of cultivated land with the Slovin method. This research is quantitative using path analysis to analyze the direct and indirect effects of exogenous variables on endogenous variables. The results showed that farmers' formal education and farming experience had a positive effect on entrepreneurial behavior. Formal education of farmers has no direct effect on farm productivity but influences entrepreneurial behavior. Farming experience has a direct effect on farm productivity and indirectly through entrepreneurial behavior. Entrepreneurial behavior has a positive effect on farm productivity. Keywords:Education, Experience, Entrepreneurial Behavior, Productivity
Examining the Role of Large Language Models in Orthopedics: Systematic Review
Authors: Zhang Cheng , Liu Shanshan , Zhou Xingyu , Zhou Siyu , Tian Yinglun , Wang Shenglin , Xu Nanfang , Li Weishi 
Published: November 2024

Background
Large language models (LLMs) can understand natural language and generate corresponding text, images, and even videos based on prompts, which holds great potential in medical scenarios. Orthopedics is a significant branch of medicine, and orthopedic diseases contribute to a significant socioeconomic burden, which could be alleviated by the application of LLMs. Several pioneers in orthopedics have conducted research on LLMs across various subspecialties to explore their performance in addressing different issues. However, there are currently few reviews and summaries of these studies, and a systematic summary of existing research is absent.

Objective
The objective of this review was to comprehensively summarize research findings on the application of LLMs in the field of orthopedics and explore the potential opportunities and challenges.

Methods
PubMed, Embase, and Cochrane Library databases were searched from January 1, 2014, to February 22, 2024, with the language limited to English. The terms, which included variants of “large language model,” “generative artificial intelligence,” “ChatGPT,” and “orthopaedics,” were divided into 2 categories: large language model and orthopedics. After completing the search, the study selection process was conducted according to the inclusion and exclusion criteria. The quality of the included studies was assessed using the revised Cochrane risk-of-bias tool for randomized trials and CONSORT-AI (Consolidated Standards of Reporting Trials–Artificial Intelligence) guidance. Data extraction and synthesis were conducted after the quality assessment.

Results
A total of 68 studies were selected. The application of LLMs in orthopedics involved the fields of clinical practice, education, research, and management. Of these 68 studies, 47 (69%) focused on clinical practice, 12 (18%) addressed orthopedic education, 8 (12%) were related to scientific research, and 1 (1%) pertained to the field of management. Of the 68 studies, only 8 (12%) recruited patients, and only 1 (1%) was a high-quality randomized controlled trial. ChatGPT was the most commonly mentioned LLM tool. There was considerable heterogeneity in the definition, measurement, and evaluation of the LLMs’ performance across the different studies. For diagnostic tasks alone, the accuracy ranged from 55% to 93%. When performing disease classification tasks, ChatGPT with GPT-4’s accuracy ranged from 2% to 100%. With regard to answering questions in orthopedic examinations, the scores ranged from 45% to 73.6% due to differences in models and test selections.

Conclusions
LLMs cannot replace orthopedic professionals in the short term. However, using LLMs as copilots could be a potential approach to effectively enhance work efficiency at present. More high-quality clinical trials are needed in the future, aiming to identify optimal applications of LLMs and advance orthopedics toward higher efficiency and precision.
Potential Inhibitor of DENV-2 Virus Protease (NS2B-NS3): An In-Silico Studies of Anti-Viral Plants
Authors: Rhakho Mhashevolu 
Published: November 2024

Dengue virus (DENV) is a mosquito-borne pathogen that affects millions of people worldwide. The DENV-2 protease is a vital enzyme responsible for viral replication and is a promising target for antiviral therapy. The objective of the study is to identify potential inhibitors of DENV-2 protease using In-Silico approaches with phytocompounds from ten antiviral plants. Initially, 133 phytoconstituents were collected with anti-dengue properties from previously reported studies which were virtually screened using SWISS ADME for ADME properties. The DENV-2 protease structure (2FOM) was obtained from the Protein Data Bank and molecular docking was performed using AutoDock Vina. The best-scoring compounds were evaluated and top five potential inhibitors with high binding affinity and stability were selected. The top-scoring compounds were Ligand-91 (Terchebin, -8.1 kcal/mol), Ligand-13 (7-desacetyl-7-benzoylgedunin, -7.8 kcal/mol), Ligand-100 (Triterpenoid, -7.8 kcal/mol), Ligand-12 (7-desacetyl-7-benzoylazadiradione, -7.7 kcal/mol), Ligand-20 (Azadirolic acid, -7.7 kcal/mol), Ref.1 (Doxycycline, -6.6 kcal/mol), Ref.2(Monosdenvir, -7.5 kcal/mol), and Ref.3 (Zanamivir, -5.6 kcal/mol). The result of the study shows that 7-desacetyl-7-benzoylazadiradione and 7-desacetyl-7-benzoylgeduninas compounds with high binding affinity for the target protein. These compounds are found in Azadirachta indica making it a promising candidate for further experimental validation and development of antiviral agents against DENV-2.
Keywords: Molecular docking, Anti-dengue, Anti-viral, ADME analysis
MOLECULAR MODELLING AND VIRTUAL SCREENING. APPLICATION TO THE COMPUTER-AIDED DESIGN OF ANTICANCER INHIBITORS WITH A FAVORABLE PHARMACOKINETIC PROFILE AGAINST E6 PAPILLOMAVIRUS TYPE 16
Authors: Bléhoué Ingrid Clémence , Koné Mawa , Esmel Elvice Akori , Fofana Issouf , Kéïta Mélalie , Megnassan Eugene 
Published: November 2024

Background: Worldwide, cervical cancer (CC) is the fourth most common women cancer. It is crucial to develop more effective treatments for this disease. We aim at designing new anticancer compounds with a favorable pharmacokinetic profile, targeting the E6 oncoprotein of human papillomavirus type 16 (HPV16 E6).
Methods: Computer-Aided Molecular Design (CAMD) has been carried out by the elaboration of a Quantitative Structure-Activity Relationship (QSAR) model of molecular complexation, through the correlation between the relative Gibbs free energy (rGFE) and the observed biological activities of a series of flavonoids inhibitors separated in training (TS) and validation sets (VS). Starting from the 3D crystallographic structure of the oncoprotein HPV16 E6 (Protein Data Banck (PDB) input code: 4GIZ), enzyme – inhibitor complexes were built by in situ modification of the native ligand (FLAV1, IC50exp= 850 nM), replacing substitution R-groups at nine different positions R1 – R9.
Results: The complexation QSAR model equation (pIC50exp=-0.5494 × DDGcom+5.9983 (1); n=16; R2=0.98) explains 98% of the variation in biological activity by that of rGFE of the analogues used. The subsequent 3D pharmacophore model (PH4) generated from the active conformations of FLAVS (pIC50exp= 1.0177× pIC50pre – 0.0927(2); n=16; R2=0.90) was used as a virtual selection tool to identify new analogues from a virtual library (VL) reaching two digits nanomolar range predicted activity.
Conclusions: The combination of molecular modelling and in silico screening of VL using the PH4 pharmacophore has led to the discovery of new promising anticancer candidates, with favorable pharmacokinetic profiles against HPV16 E6. Among them, the top two predicted respective inhibitory powers IC50 pre (50 nM and 61 nM).

Peer Review History:
Received 11 July 2024; Reviewed 16 September 2024; Accepted 20 October; Available online 15 November 2024
Academic Editor: Dr. Gehan Fawzy Abdel Raoof Kandeel, Pharmacognosy Department, National Research Centre, Dokki, 12622, Giza, Egypt, gehankandeel9@yahoo.com
Average Peer review marks at initial stage: 6.5/10
Average Peer review marks at publication stage: 8.5/10
Reviewers:
Dr. Ogbonna B. Onyebuchi, Nnamdi Azikiwe University, Awka, Nigeria, summitpharm@yahoo.com
Prof. Syamsudin Abdillah, Pancasila University, Indonesia, syamsudin.abdillah@gmail.com
Momento de la suplementación sobre carga animal y producción de leche por hectárea de vacas Holstein en pastoreo
Authors: Castro Jaime Citlali Anais , Ramírez Valverde Rodolfo , Burgueño Ferreira Juan Andrés , Ramírez-Bribiesca Jacinto Efrén , Miranda Romero Luis Alberto , Améndola Massiotti Ricardo Daniel 
Published: November 2024

El objetivo fue evaluar, en pastoreo de praderas mixta de Medicago sativa L. y Dactylis glomerata L., la respuesta de vacas Holstein Neozelandés a la suplementación con concentrado en diferentes momentos del día, sobre producción individual, carga animal y producción de leche por hectárea. Se realizaron dos experimentos, en invierno y en primavera-verano, con un diseño cruzado 3×3. Los tratamientos fueron tres momentos de oferta de concentrado (5.0 kg de MS vaca-1 día-1) como suplemento luego de la ordeña matinal (AM), de la vespertina (PM), y dividido equitativamente en ambas ordeñas (AM-PM). Las unidades experimentales fueron lotes de seis (invierno) o cinco vacas (primavera-verano) y sus respectivas áreas de pastoreo, mismas que recibieron los tratamientos. El criterio de manejo del pastoreo rotacional fue 8 cm de altura de forraje residual para todos los tratamientos; esto permitió estimar el efecto de los tratamientos sobre la carga animal. No hubo efecto (P>0.05) sobre carga animal. La producción de leche por vaca en AM fue 10.2 % superior que los otros dos tratamientos en promedio, tanto en invierno (8.6 %, P=0.0002), como en primavera-verano (11.7 %, P<0.0001). El incremento en producción de leche por ha (9 %) se debió a la respuesta individual y no a diferencias en carga animal. El criterio de manejo de pastoreo con altura única de forraje residual permitió, de modo sencillo, estimar la respuesta en carga animal y con ello la producción de leche por hectárea.
Manejo del pasto elefante de riego intercalado con leguminosas en la región semiárida
Authors: do Vale Bezerra Jéssica Daisy , Emerenciano Neto João Virgínio , Da Cruz da Silva Tamiris , Fernandes Patrick Bezerra , Antas Urbano Stela , Pontes Teixeira das Chagas Felipe , Dos Santos Difante Gelson , Geraldo Costa Marcone , Chaves Gurgel Antonio Leandro , Lopes Sousa Francisco Israel , Da Silva Santos Rodrigo , Graciano da Costa Ana Beatriz 
Published: November 2024

El presente estudio tuvo como objetivo evaluar la producción y composición química del pasto elefante (Pennisetum purpureum sin. Cenchrus purpureus cv. Mott) intercalado con Cajanus cajan (Mandarim y Fava Larga) y Stylosanthes guianensis (Bela) en comparación con su cultivo en monocultivo bajo manejo de riego en la región semiárida. El experimento se llevó a cabo en el Campus de Ciencias Agrícolas de la Universidad Federal del Valle de São Francisco, Petrolina, Brasil. El experimento consistió en los siguientes tratamientos: pasto elefante intercalado con cada leguminosa y dos tipos de monocultivo, uno con fertilización nitrogenada (200 kg ha-1) y el otro sin ella. Las leguminosas ayudaron a mejorar la calidad del dosel forrajero, con altos niveles de proteína cruda. La fertilización nitrogenada aumentó la masa de forraje producido por el pasto elefante. El análisis acumulativo de todos los cortes mostró que el cultivo intercalado de elefante con el cultivar Bela logró el mayor rendimiento, con 13.49 Mg ha-1, debido principalmente al aumento en la población de Bela, que demostró ser superior a las otras leguminosas a lo largo de los cortes. Con base en los resultados, se recomienda el cultivo intercalado de elefante con el cultivar Bela como la estrategia más efectiva para maximizar la producción de forraje en la región semiárida.
usabilidade e o comportamento informacional como estratégia de melhoria do Portal de Transparência da UFRN
Authors: Bezerra de Araujo Saul Lincoln 
Published: November 2024

O presente artigo tem como objetivo abordar a importância da usabilidade e do comportamento informacional como estratégia de melhoria do portal de transparência da UFRN e avaliar como as informações estão dispostas em seu portal. Assim, dentro dessa temática, pode-se observar que, mesmo com os dispositivos legais que disciplinam o tema, é preciso que melhorias e correções sejam realizadas dentro desse complexo arcabouço conceitual. Dada a importância dos portais de transparência como uma maneira de exercer a cidadania, fiscalizar e contribuir no combate a corrupção é dever dos órgãos disponibilizarem as informações necessárias e que as mesmas estejam em uma linguagem focada no usuário. Como metodologia trata-se de uma pesquisa com abordagem qualitativa; quanto aos meios, utiliza-se a pesquisa bibliográfica juntamente com a análise do portal da UFRN; quanto aos fins, classifica-se como uma pesquisa descritiva. Desse modo, a formação de critérios que padronizem a maneira de como se dá a apresentação das informações, contribuem para que os usuários se sintam mais confortáveis ao efetuarem a busca por estas. Assim, todo esse contexto, vai ao encontro da forma direta e efetiva para o fortalecimento de um estado democrático e participativo no combate a corrupção.
Juridical Reasoning for the Distribution of Pharmaceutical Preparations that Failed the Efficacy Test in Court Decisions
Authors: Febriansyah Ferry Irawan , Richard Tomlins  , Ulya Shafa Firdausi  , Yusuf Adam Hilman  
Published: November 2024

ABSTRACT
Purpose of thestudy (Tujuan) : The purpose of this research is to determine the judge's considerations in imposing sanctions on pharmaceutical distributors who do not meet the efficacy and quality standards by the Ponorogo district court decision Number 115/Pid.Sus/2023/PN Png using juridical analysis.
Methodology (Metodologi): The methodology used is a normative research method or library research method.
Results (Temuan): The results of this research are that there are cases of distribution of drugs that do not match the efficacy and quality, violating the protection rights of consumers. The government and BPOM are expected to pay more attention to the pharmaceutical production process and provide education to the lay public in the pharmaceutical sector so that the public obtain safe and quality pharmaceutical products. Ponorogo District Court Decision Number 115/Pid, Sus/2023/PN Png The panel of judges considered evidence, legal interpretation, and ethics during the trial. This case violates Law Number 36 of 2009 Article 196 concerning Health. By considering this, circumstances emerged that mitigated and aggravated the defendant and also used the theory of will and the theory of knowledge so that he was charged with imprisonment for 1 (one) year and a fine of IDR 5,000,000.00 (five million rupiah) provided that the fine was not paid to be replaced by imprisonment for one month. The decision at the Ponorogo District Court provides a solid foundation for future courts in handling similar cases.
Applications of this study (Kegunaan): The use of this research can be an in-depth understanding of the decision ratio in the Ponorogo District Court Decision for both perpetrators, legal practitioners, academics, and policymakers for future directions.
Novelty/ Orginalty of this study (Kebaruan/Orisinalitas): The difference with previous studies is that the focus of this research is the location of the research, the type of drug used and the district court decision
Bioplastic made from Kiwi Branches
Authors: Charchalis Maria , Monteiro Fernando , Kit Yasmina 
Published: November 2024

The main goal of this work was to develop a product whose cellulose is extracted from kiwi branches. The product presented, Kiwiplast consists of a bioplastic film for food packaging. This way, it intends to create a circular economy and lower environmental impact. The extraction and production process were studied and scaled up to industrial level. The company would be located in Agueda, with a working force of 10 workers. An economic analysis has shown that this project requires an investment of 896 k€ and is viable and profitable.
Critical Analysis of Rio de Janeiro’s Compulsory Audit Reports
Authors: Rangel Danilo Chaves , Guimarães Claudinei de Souza , Meza Lidia Angulo 
Published: November 2024

Objective: The objective of this study was to analyze compulsory environmental audit reports, with the aim of finding common points and divergences in the Audit Evidence, Environmental Performance Analysis and Action Plan Sections of each report.

Theoretical Framework: In this topic, discussions on mandatory environmental audits, conceptualization of environmental performance and its analysis are presented, providing a solid basis for understanding the context of the analysis.

Method: The methodology adopted for this research comprised the exploratory analysis of 14 compulsory audit reports to identify common points between them. The reports were collected from those available for public access in the Inea Central Library, under the criterion of homogeneity regarding the description of each company's activities.

Results and Discussion: The study pointed out that there is a great discrepancy between the approaches of audit teams, especially regarding methodologies for analyzing environmental performance in the context of audits. Such findings indicate the need for alignment, performance analysis approaches and standardization of environmental indicators.

Research Implications: The present study brings implications to the field of Environmental Performance Audits, guided by changes in field practices and the theoretical approach to the topic, in order to bring reflections on the improvements necessary to provide greater potential and alignment of the instrument with the current context of Sustainability of the state productive sector.

Originality/Value: There are few studies on the subject of compulsory environmental audits in the State of Rio de Janeiro and, therefore, this study expands the reflections on the use and role of this instrument as part of the State Environmental Policy.
Analysis Of Opportunities For Implementing The Amicus Curiae Concept As A Form Of Public Participation In The Judicial System In Indonesia
Authors: Thomas Jerry , Liman Vivaldi 
Published: November 2024

This research uses the normative juridical method, and it aims to determine the amicus curiae mechanism in the Indonesian legal system. The research results show that the implementation of amicus curiae in the judicial system in Indonesia still needs a common perspective among judges, where there are still judges who accept or reject this concept or do not even consider it at all. The concept of amicus curiae in the Indonesian legal system has yet to be a significant consideration because no explicit regulations accommodate it. Still, it is often stated that the position of amicus curiae is embodied through Article 5 of Act Number 48 of 2009 on Judicial Power, which mandates judges to explore, follow, and understand legal values and a sense of justice that lives in society. In line with these provisions, the judge has the authority to provide space and open up the broadest possible information and opinions from various groups who pay special attention to a case being examined. Judges using amicus curiae in their considerations, both from a philosophical, sociological, and juridical perspective, aim to prioritize legal certainty and provide justice with the participation of society. The research then provides a suggestion that the Supreme Court of the Republic of Indonesia can issue a Policy Circular or through a Decree of the Chief Justice of the Supreme Court regarding guidelines that judges can use to implement amicus curiae and how to assess the quality of information in amicus curiae.