bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disruption of Oncogenic MCL-1-BAX/BAK Interaction Using Integrase Inhibitors: Insights from a Molecular Docking and Dynamic Exploration
Authors: Anifowose Lateef O. , Adegboyega Fikayo N. , Ogunyemi Oludare M. , Akano Rukayat O. , Adeyemo-Salami Oluwatoyin A. , Hammad Sherif F. , Ghazy Mohamed A. 
Published: May 2024

Abstract

Dysregulation of programmed cell death is a hallmark characteristic of cancer cells, making the apoptotic signaling pathway of important clinical relevance in cancer therapy. In mammalian cells, this critical cellular event is negatively regulated by antiapoptotic BCL-2 proteins. Notably, overexpression of Myeloid Cell Leukemia-1 (MCL-1) has emerged as a survival and drug resistance mechanism in several malignancies. Given its high oncogenic potential, MCL-1 represents an attractive therapeutic target for solid and hematological tumors. Oncological drug development is prohibitively expensive, time-consuming, and has a poor success rate due to toxic side effects. Thus, repurposing existing approved drugs with demonstrated safety profiles denotes a promising strategy for rapidly and economically discovering drugs in cancer medicine. Herein, we used a virtual computing technique to screen a customized library of thirty-one antiviral drugs for potential antagonistic activity against MCL-1. Our molecular docking experiment uncovered bictegravir and cabotegravir as promising inhibitors of MCL-1 in comparison to the reference clinical inhibitor (AMG176) based on superior binding affinity and strong interactions with the protein hotspots residues. Further, these integrase inhibitors exhibited appealing pharmacokinetic and toxicity profiles. Noteworthy, the thermodynamic parameters studied during the 100 ns molecular dynamics (MD) simulation and principal component analysis of the MD trajectory exemplify these drugs' structural stability and conformational flexibility in the protein active pocket. Our findings suggest that these integrase inhibitors could be repurposed for cancers overexpressing MCL-1. However, further studies involving experimental biological models are required to unravel their novel anticancer activity and ascertain their clinical efficacy in cancer treatment.
Deregulation of cellulose synthesis by site-directed mutagenesis of cellulose synthase leads to heightened bacterial cellulose production
Authors: Upton Daniel J. , Eastmond Heather , Gatenby Angharad , Lanot Alexandra , Bruce Neil C. 
Published: May 2024

Abstract

Background Bacterial cellulose produced via fermentation is a promising alternative to plant-derived cellulose with the potential to provide a sustainable source of cellulose with a significantly lower environmental footprint than unsustainable sources of cellulose such as wood pulp. Optimisation of the production system is needed to raise productivity and achieve commercial viability. The organism used is a key component of this system and a key target for optimisation by strain development procedures. Wild strains of cellulose-producing bacteria regulate their cellulose synthesis in response to the environment. Deregulation of cellulose synthesis is necessary to achieve higher yields. A key regulatory target for strain engineering is the post-translational deregulation of cellulose synthase that is regulated by cyclic-di-GMP. It has been demonstrated in vitro that mutating the N-terminal arginine residue of the RXXXR motif creates a constitutively active cellulose synthase, but its in vivo effect has not yet been explored.Results In this study, we investigate the effect of mutating the N-terminal arginine residue of the RXXXR motif in vivo with a wild strain of cellulose-producing bacteria isolated in this work. We show heightened bacterial cellulose production in both static and shake flask fermentation when mutated cellulose synthase is expressed compared to when native cellulose synthase is expressed.Conclusions Our work shows for the first time to our knowledge the in vivo effect when the deregulated mutant variant of cellulose synthase is expressed. This work builds on previous studies and furthers progress towards the goal of creating an optimised cellulose-producing strain capable of commercially viable bacterial cellulose production. The work also highlights the importance of elucidating and disrupting the regulatory mechanisms that govern cellulose synthesis, and the challenging nature of this field.
Heavy metal contamination in Sungai Petani, Malaysia: a wastewater-based epidemiology study
Authors: Ruzi Iqbal Iman , Ishak Ahmad Razali , Abdullah Muhamad Azwat , Zain Nur Nadhirah Mohamad , Tualeka Abdul Rohim , Adriyani Retno , Mohamed Rafeezul , Edinur Hisham Atan , Aziz Mohd Yusmaidie 
Published: May 2024

ABSTRACT

The aim of this study was to investigate the use of wastewater-based epidemiology (WBE) to estimate heavy metal exposure in Sungai Petani, Malaysia. Atomic absorption spectroscopy was used to detect copper (Cu), nickel (Ni), zinc (Zn), iron (Fe), and cadmium (Cd) in wastewater from eight sewage treatment facilities in Sungai Petani in January 2022. The heavy metal concentrations were measured in both influent and effluent, and the mean concentrations in the wastewater were found to be in the following order: Fe &gt; Ni &gt; Zn &gt; Cd &gt; Cu, with a 100% detection frequency. The results of WBE estimation showed that Fe, Ni, and Zn had the highest estimated per population exposure levels, while Cd had the lowest. Compared to a similar study conducted in Penang, Malaysia, all metals except Cu were found to have higher concentrations in Sungai Petani, even though it is a non-industrial district. These findings highlight the importance of addressing heavy metal contamination in Sungai Petani and implementing effective risk management and prevention strategies.
Assessment of microplastics and associated ecological risk in the Hirakud Reservoir, Odisha, India
Authors: Patra Kiran Bala , Baitharu Iswar 
Published: May 2024

ABSTRACT

Microplastic has emerged as a global threat owing to its chronic ubiquity and persistence. Microplastics’ small size expedites their ingestion at each trophic level causing biomagnification and bioaccumulation, which has raised public concerns. The present study isolated, quantified and characterized the abundance, shape, size, color, and chemical composition of the microplastics from water and sediments of the Hirakud Reservoir through a scanning electron microscope and FTIR. The ecological risk associated with the microplastics was assessed using the species sensitivity distribution (SSD) method to derive the Predicted No-Effect Concentration (PNEC) value and risk quotient (RQ). The abundance of microplastics in the surface water and sediments of the Hirakud Reservoir was estimated at 82–89 particles/L and 159–163 particles/kg, respectively. Fiber-shaped microplastics dominated both surface water (46.21%) and sediment samples (44.86%). Small-sized microplastics (53–300 μm) prevailed in all samples. Color delineation exhibited an abundance of transparent microplastics. Chemical characterization indicated the dominance of polypropylene (38%), followed by high-density polyethylene, low-density polyethylene, and polystyrene. The calculated PNEC value was 3,954 particles/m3, and the RQ was estimated to be 0.02073–0.04122 indicating negligible ecological risk to freshwater species in all the sampling sites.
The Institutional Environment as a Tool for Managing the Development of the Region in the Context of Digitalization
Authors: Yakushkina T. A. , Partnenko S. I. , Mokretsova A. I. 
Published: May 2024

Relevance. In the context of digitalization and digital transformation, the institutional environment can be considered as a tool for managing the development of the region. This circumstance predetermined the choice of topic and proved its relevance.The purpose of the study is to study the institutional environment as a tool for managing the development of the region in the context of digitalization.Objectives: the management of the implementation of state programs in the context of digital transformation, compliance with the requirements of federal and regional legislation regulating project activities, the possibility of regulating the mechanisms of project management of regional programs are considered; the role of project management is considered as an effective tool for the implementation of national projects in changing conditions, ensuring the achievement of national goals.Methodology. In the process of carrying out the work, analytical methods were used to study the mechanisms of regional management, including digital technologies and their impact on the efficiency of management processes.Results. As a result of the work on this study, it was revealed that project management of government programs today comes to the fore. project management has a fundamental difference in terms of integration and synchronization of target indicators of state programs, taking into account the requirements of legislation at the federal and regional levels. More significant factors of the internal and external environment are identified that influence the result during project management, regulatory regulation, monitoring control points, and assessing the effectiveness of using the resource potential of the region, the ability to make timely adjustments during the implementation of activities by responsible participants to achieve results, for which it is necessary to simplify the adjustment procedure.Conclusions. When forming government programs, it is important to assess the impact of the process of organizing project activities in each region. Compliance with the requirements of regulatory legal acts and other methodological frameworks regulating the organization of project activities, as well as the effectiveness and efficiency of regional programs is assessed. In this regard, improving the legislation regulating project activities in order to ensure the implementation of national projects will strengthen the possibilities for the transition of the real sector of the economy to a digital format.
MANEJO DE ÁGUA E DOSES DE NITROGÊNIO NA PRODUÇÃO DE MASSA SECA EM ARROZ IRRIGADO
Authors: Radmann Vairton , Costa Nogueira Matheus , Mantovanelli Bruno Campos , Mendonça Leite Matheus , Freire das Chagas Márcio , Silva Patrícia 
Published: May 2024

A escassez e o elevado custo para conduzir a água até a lavoura de arroz irrigado, podem tornar a lavoura arrozeira impraticável financeiramente. No entanto, a presença da lâmina de água no arroz irrigado é fundamental no controle da amplitude térmica, aumento na disponibilidade de nutrientes e controle de ervas daninhas. O nitrogênio é considerado o elemento de maior exigência da cultura, em doses inadequadas, pode contribuir de forma negativa no arroz, como: aumento de doenças, grãos quebrados, diminuição no rendimento. Desde modo, foi realizado o presente estudo para avaliar o número de perfilhos e massa seca da parte aérea do arroz, submetido à diferentes manejos de água e doses de nitrogênio. O experimento foi conduzido em delineamento de blocos casualizados, em esquema fatorial 3 x 4 com 3 repetições. Os fatores foram com manejo de água com três níveis: alagado, saturado e capacidade de campo, e doses de nitrogênio com quatro níveis: 0, 50, 100 e 150 kg ha-1 de nitrogênio. Os dados foram submetidos ao teste F para a análise de variância. Quando significativos foi aplicado o teste de médias Tukey a 5% de probabilidade. Para as doses de nitrogênio em cada manejo, foi realizada a análise de regressão. O aumento das doses de nitrogênio proporciona o aumento do número de perfilhos. O manejo saturado proporciona aumento no número de perfilhos. O aumento das doses de nitrogênio proporciona aumento de massa seca da parte aérea no manejo saturado. A maior massa seca da parte aérea ocorre no manejo saturado na dose de 150 kg ha-1 de nitrogênio.
IDENTIFICAÇÃO DOS RECURSOS E DAS ESTRATÉGIAS DIRECIONADAS AO SUPORTE AOS DISCENTES SURDOS NA EDUCAÇÃO PROFISSIONAL E TECNOLOGICA: UM RECORTE IMERSIVO NAS DISSERTAÇÕES DO PROGRAMA DE MESTRADO EM EDUCAÇÃO PROFISSIONAL E TÉCNOLÓGICA (PROFEPT)
Authors: Castro Andréa Cardoso , Castro Marcos Paulo de Assis , Seixas Luma da Rocha , Melo Rosangela Maria de , Melo Filho Ivanildo José de 
Published: May 2024

Este estudo tem como propósito identificar e refletir quais trabalhos trazem recursos ou estratégias direcionadas à população de discentes Surdos, de forma a incluí-los no contexto educacional na Educação Profissional e Tecnológica (EPT) a partir das dissertações desenvolvidas no Programa de Mestrado em Educação Profissional e Tecnológica (PROFEPT) no recorte temporal entre 2017 a 2021. Para tanto, um protocolo de Revisão Sistemática da Literatura (RSL) foi elaborado de modo a selecionar os trabalhos associados com a temática do estudo que abordassem sobre os recursos ou estratégias direcionadas à população de discentes Surdos, de forma a incluí-los no contexto educacional na Educação Profissional e Tecnológica (EPT). A RSL foi dividida em 03(três) fases a saber: planejamento, condução e relatório. Os mecanismos de buscas adotados foram: (i) o Catálogo de Teses de Dissertação da CAPES, (ii) o Observatório do PROFPET e (iii) a Plataforma Sucupira. Os resultados oriundos da RSL evidenciam, de uma forma geral, que apesar das dificuldades no cotidiano dos estudantes dos Surdos na EPT, as iniciativas levantadas, seguramente evidenciam um avanço significativo na inclusão desses estudantes. Os recursos identificados nos trabalhos selecionados foram agrupados de acordo com as suas similaridades. Esses agrupamentos favoreceram a visualização das recorrências da tipologia, do público-alvo e da superação da barreira que cada produto desenvolvido visou contribuir. A inclusão dos estudantes Surdos no contexto educacional nos Institutos Federais, apesar de ser uma realidade, ainda requer empenho e dedicação minuciosa para que os recursos desenvolvidos ou os produtos educacionais no contexto do PROFFEPT saiam do campo das ideias e passem a ser realidade nessas Instituições. Por fim, os resultados, sinalizam a importância do desenvolvimento de produtos educacionais de forma que sejam utilizados como um instrumento de apoio para a quebra das barreiras que impedem a inclusão dos discentes Surdos na EPT. Palavras chave: Inclusão; Surdo; Surdez; Educação Profissional e Tecnológica; Instituto Federal de Educação, Ciência e Tecnologia; PROFEPT.
UM ESTUDO BIBLIOMÉTRICO SOBRE TEORIA DAS FILAS ENTRE OS ANOS DE 2011 A 2021
Authors: Ricardo Jonas da Conceição , De Freitas Renildes Matos , De Freitas Renildes Matos , Pereira Teixeira Camila Oliveira , Pereira Teixeira Camila Oliveira 
Published: May 2024

O presente trabalho é uma pesquisa bibliográfica descritiva, cuja sua análise foi feita pelo método misto(qualitativa-quantitativa) com a finalidade de conhecer melhor a área onde é aplicada a teoria das filas. Como método para essa pesquisa foram analisados 92 artigos do Encontro Nacional de Engenharia de Produção (ENEGEP) ocorrido entre os anos de 2011 a 2021. Neste trabalho foram analisados a distribuição temporal das publicações, quais os softwares eram utilizados e quais as áreas onde eram empregados o estudo das Teoria das Filas. Em uma segunda análise foram pesquisadas como os termos que descrevem esses artigos sobre teoria das filas, as palavras-chave, se relacionavam com a temática central, sendo esse estudo feito por meio de Análise de Redes Sociais(ARS). Como resultado da pesquisa foi possível a verificação do Microsoft Excel, Arena e Promodel como sendo os softwares mais utilizados e a aplicação das teorias das filas em situações diversas, como por exemplo supermercado, filas de bancos, hospitais e supermercado, fato que também se repete ao observarmos as análises das palavras-chave pelos estudos das centralidades de grau e de proximidade
Populasi, Serangan dan Pola Distribusi Hypothenemus hampei Ferr. pada Kopi Arabika Gayo Berdasarkan Zona Elevasi
Authors: Hendrival Hendrival , Usnawiyah Usnawiyah , Nurdin Muhammad Yusuf , Ahmadika Hafizh Mulia , Margono Margono 
Published: May 2024

Provinsi Aceh sebagai sentral penghasil kopi arabika berada di Dataran Tinggi Gayo yaitu Kabupaten Bener Meriah. Faktor yang menyebabkan produksi kopi arabika tergolong rendah yaitu serangan hama penggerek buah kopi, Hypothenemus hampei Ferr. Hama ini termasuk hama utama yang paling merugikan yang menyebabkan kerugian kuantitatif dan kualitatif pada kopi arabika dan robusta. Pola sebaran H. hampei dipengaruhi oleh zona elevasi. Penelitian ini bertujuan untuk mempelajari pola sebaran hama H. hampei pada kopi arabika Gayo berdasarkan elevasi. Lokasi penelitian mencakup wilayah perkebunan kopi arabika milik petani di Kecamatan Bukit, Timang Gajah, dan Pintu Rime Gayo di Kabupaten Bener Meriah Provinsi Aceh dengan waktu penelitian dari bulan Juli sampai dengan Desember 2021. Lokasi yang dipilih sebagai tempat pengamatan dan pengambilan sampel yaitu perkebunan kopi rakyat dengan variasi zona elevasi. Setiap wilayah ditentukan dua titik lokasi pengamatan dan pengambilan sampel. Hasil penelitian menunjukkan bahwa populasi dan serangan hama H. hampei pada kelompok zona elevasi rendah (700 mdpl–1000 mdpl) tergolong tinggi dibandingkan kelompok ketinggian medium (1000–1250 mdpl) dan tinggi (1250–1500 mdpl). Pola sebaran hama H. hampei pada kopi arabika Gayo pada parameter populasi dan serangan mengikuti pola mengelompok berdasarkan perbedaan zona elevasi. Tindakan monitoring populasi dan serangan hama H. hampei diperlukan untuk mengurangi penurunan produksi kopi arabika Gayo terutama di daerah dengan zona elevasi antara 700–1000 mdpl.
La Inteligencia Artificial Generativa en la Enseñanza Media. Propuesta de formación de docentes
Authors: González Alejandro , Portillo Juan José , Zangara María Alejandra 
Published: May 2024

El impacto que ha generado la aparición de las nuevas herramientas de Inteligencia Artificial Generativa (IAG) en todos los ámbitos de la vida cotidiana sacudió también, indudablemente, a los procesos de enseñanza y aprendizaje dentro del sistema educativo. Con la intención de empezar a bocetar respuestas a este desafío generamos un seminario de formación para docentes del nivel medio, que implementamos en el Colegio Nacional “Rafael Hernandez” de la UNLP y de cuya experiencia queremos hablar aquí.
En la introducción, iniciaremos con la motivación que llevó a la construcción de este plan. A continuación definiremos y hablaremos de cómo funciona la IAG. Luego tendremos un apartado sobre IAG en educación media (con herramientas y propuestas de uso). Finalmente, presentaremos la aplicación práctica de los temas trabajados en el Taller de uso de IAG en la enseñanza media, donde se buscó construir una propuesta pedagógica con el uso de IAG para el aula. Además, presentaremos una evaluación FODA de estas herramientas y describiremos cuáles fueron sus resultados preliminares.
Antropofagia, incisões corporais, terra sem mal: os mortos e a territorialidade tupi nos séculos XVI e XVII
Authors: Cymbalista Renato 
Published: May 2024

O processo de ocupação do território americano pelos europeus, nos séculos XVI e XVII, significou não apenas a submissão ou a expulsão dos índios, mas também a destruição de formas especificas de territorialização, incompatíveis com a empresa colonial. Este texto busca contribuir para a compreensão de como os índios tupi da costa brasileira construíam uma ideia de território, em termos muito diferentes daqueles operados pelos europeus. O foco específico são as formas de relacionamento entre os vivos e os mortos, que o texto defende ser uma chave de explicação eficaz para compreender aspectos da territorialidade dos índios. Utiliza-se de fontes do inicio da Idade Moderna, que mostram uma mentalidade européia profundamente marcada pela religiosidade, que identificava, na cultura dos índios, elementos que por vezes os olhos contemporâneos captam com mais dificuldade. As relações entre vivos e mortos são investigadas no texto a partir de três elementos inter-relacionados: as migrações em busca da imortalidade, a antropofagia e as incisões corporais que registravam os guerreiros mortos em combate.
Multistrain probiotics fail to modulate the asthmatic phenotype, respiratory microbiota, and immune responses in cats
Authors: Remaks Julia D. , Vientos-Plotts Aida I. , Rindt Hansjorg , McAdams Zachary , Ericsson Aaron C. , Reinero Carol R. 
Published: May 2024

Abstract

OBJECTIVE
To determine if multistrain probiotics administered to asthmatic cats treated with anti-inflammatory glucocorticoids would attenuate the asthmatic phenotype and beneficially alter respiratory, blood, and oropharyngeal (OP) microbial communities and immune parameters versus placebo.

ANIMALS
13 client-owned asthmatic cats.

METHODS
A randomized, blinded, placebo-controlled clinical trial of asthmatic cats receiving anti-inflammatory glucocorticoids with oral multistrain probiotics or placebo assessed owner-perceived improvement and airway eosinophilia at baseline and after 2 weeks of treatment. Bronchoalveolar lavage fluid (BALF), blood, OP, and rectal microbial communities were compared using 16S rRNA amplicon sequencing. Real-time PCR for transcription factors, activation markers and cytokines, and IgA ELISAs were evaluated. Statistical analyses used 2-way repeated-measures ANOVA or permutational ANOVA (significance, P < .05).

RESULTS
After treatment, there were no significant differences in owner-perceived clinical signs or mean ± SEM BALF eosinophils between groups. There was a significant decrease in rectal α-diversity but not in α- or β-diversity in BALF, blood, or OP between groups or over time. There were no significant differences in CD25, FoxP3, GATA, Helios, IL-4, IL-5, IL-10, IL-13, IL-17, IFN-γ mRNA, or serum or BALF IgA between groups or over time.

CLINICAL RELEVANCE
In asthmatic cats, oral multistrain probiotics failed to improve owner-perceived signs, reduce airway eosinophilia, modify microbial community composition, or alter assessed immune responses versus placebo or over time. Longer treatment, different probiotic composition or delivery (eg, aerosolized), or larger number of cats would represent the next stages of study.
Constrictive physiology is not present in all dogs with idiopathic chylothorax
Authors: Adams Taylor E. , Marvel Sarah J. , Monnet Eric 
Published: May 2024

Abstract

OBJECTIVE
To determine whether subtotal pericardectomy affects recurrence and long-term outcomes in dogs with idiopathic chylothorax (IC).

ANIMALS
12 client-owned dogs diagnosed with IC between July 26, 2016, and March 23, 2023.

METHODS
The diagnosis of constrictive physiology (CP) was established with cardiac catheterization and defined as elevated and equal diastolic pressures in all 4 cardiac chambers. Dogs were then entered into the constrictive physiology (CP) group or non-CP (NCP) group. All dogs received at least a thoracic duct ligation (TDL). The dogs in the CP group had a subtotal pericardectomy performed in addition to TDL. Repeated surgical interventions, recurrence, long-term outcomes, and survival times were recorded.

RESULTS
8 dogs were entered into the CP group and underwent TDL and subtotal pericardectomy. Four dogs were entered in the NCP group and underwent only a TDL. Four dogs in the CP group and 1 in the NCP group required multiple surgeries for recurrent chylothorax. The 1-, 2-, and 3-year disease-free rates were, respectively, 100%, 100%, and 50% for the NCP group and 87.5%, 72.9%, and 72.9% for the CP group (P = .935). The 1-, 2-, and 3-year survival rates were, respectively, 100%, 100%, and 100% for the NCP group and 87.5%, 72.9%, and 72.9% for the CP group (P = .317).

CLINICAL RELEVANCE
Constrictive physiology should be evaluated by cardiac catheterization before surgical treatment of IC in dogs. If CP is not diagnosed, subtotal pericardectomy may not be required.