bluuebunny/crossref_metadata_2025 huggingface dataset:
Оптимізація витрат на маркетинг та рекламу як засоби інноваційної маркетингової політики підприємства
Authors: Гаврюшенко Г.В.
Published: September 2024

У статті наголошено на тому, що маркетинг та реклама є важливими аспектами будь-якого бізнесу, однак часто вони потребують значних витрат. Зазначено, що оптимізація витрат на маркетинг та рекламу виступає елементом інноваційної маркетингової політики підприємства, дозволяючи більш ефективно використовувати ресурси та впроваджувати новаторські стратегії. Бізнеси, які ефективно оптимізують свої витрати, мають перевагу перед конкурентами. Зазначено, що основними аспектами, що можуть призводити до проблем в частині оптимізації витрат на маркетинг та рекламу, є: брак або недостатність даних про ефективність рекламних кампаній; недостатня цільова спрямованість реклами; низька якість рекламного контенту; неправильний вибір каналів реклами; нестабільні ринкові умови; неправильна стратегія цінової політики; непослідовність і недостатній моніторинг. Наголошено на тому, що для оптимізації витрат на маркетинг та рекламу необхідно запровадити систему оперативного отримання інформації про ефективність як окремих маркетингових заходів, так і маркетингової діяльності загалом. Зазначено, що контроль роботи маркетологів об’єктивний лише у разі дотримання правила: «Необхідне планування з чіткими кількісними показниками». Запропоновано виділяти три основні етапи оцінки роботи маркетологів при впровадженні інноваційної маркетингової політики підприємства, а саме:1 етап – постановка завдань, що включає вивчення організації, визначення товарів/послуг, що дають прибуток, вивчення контрагентів, моніторинг інформаційного поля, складання бюджету на рекламу та маркетинг; 2 етап – оцінка результатів, що передбачає установлення планових величин (показники у бюджетах), розрахунок ефективності витрат на рекламу, оцінка якості роботи зі споживачами (виміряти цей показник можна за допомогою опитування цільової аудиторії), рівень рекламної поінформованості, тобто розуміння, наскільки співробітники знають кон’юнктуру ринку, поінформовані про нові продукти та діяльність конкурентів; 3 етап – підготовка програми коригувальних заходів, що передбачає розроблення плану коригувальних заходів на майбутній період, призначення відповідальних за їх виконання, встановлення конкретних термінів виправлення невідповідностей. Програма повинна включати ті дії, які допоможуть виключити виявлені негативні сторони роботи маркетингової служби. Наголошено на тому, що оптимізація витрат на маркетинг та рекламу потребує системного підходу та постійного аналізу результатів для забезпечення максимальної ефективності інноваційної маркетингової політики підприємства.
PENGARUH STRUKTUR MODAL, KINERJA KEUANGAN, PERTUMBUHAN DAN UKURAN BANK TERHADAP NILAI BANK YANG TERDAFTAR DI BURSA EFEK INDONESIA (BEI)
Authors: Vebry Charolina  , Eddy Suranta
Published: September 2024

This study aims to provide empirical evidence of the influence of capital structure, financial performance, growth, and bank size on the value of Islamic banks listed on the Indonesia Stock Exchange (IDX) using the observation period from 2014 - 2019. Data collection methods using a purposive sampling method using quarterly financial statement data so that the number of observations amounted to 29 observations.
 
The test results show that the ratio of capital structure (DER) and financial performance (ROA) as a proxy for financial performance affect the value of Islamic banks while the growth and size of the company does not affect the value of Islamic banks.
PENGARUH PENERAPAN SIA, BUDAYA ORGANISASI, KESESUAIAN TUGAS DAN MOTIVASI KERJA TERHADAP KINERJA KARYAWAN BAGIAN AKUNTANSI (STUDI EMPIRIS PADA PERUSAHAAN BUMN DI KOTA BENGKULU)
Authors: Elsa Purnama Sari  , Isma Coryanata
Published: September 2024

This study aims to examine the effect of applying accounting information systems, organizational culture, suitability of task-technology and work motivation on the performance of accounting department employees at BUMN in Bengkulu City. The data used in this study are primary data. Primary data were obtained from a questionnaire distributed to employees of the accounting department at the BUMN in Bengkulu City. The number of questionnaires distributed was 38 questionnaires, but only 36 questionnaires could be processed. Data were analyzed using multiple linear regression analysis using the SPSS program.
The results showed that the application of the accounting information system, organizational culture, task- technology suitability and work motivation had a positive effect on the performance of the accounting department employees at BUMN in Bengkulu City. This research can contribute to SOEs in the city of Bengkulu to be taken into consideration in order to continue to improve the performance of employees in accounting in every company. As for the limitations of this study, this study cannot reach all BUMNs in Bengkulu City because there are a number of BUMN companies that are not willing to be used as research samples.
INKLUZÍVNY TREND A DIDAKTICKÉ VÝZVY V EDUKÁCII ŠTUDENTOV UČITEĽSTVA
Authors:   University of Trnava, Balážová Jana , Bilčík Alexander ,   Tomas Bata University in Zlín
Published: September 2024

INCLUSIVE TREND AND DIDACTIC CHALLENGES IN THE EDUCATION OF STUDENTS OF TEACHING The authors present didactic challenges in connection with the inclusive trend and education reform, which require changes in the training of future teachers, educators, and teaching assistants. The teacher's intention in educating pupils should be to achieve mutual enrichment and support on the common path to knowledge. Part of the contribution is an outline of the complexity in the didactic preparation of students of teaching and a demonstration of the variety of possibilities in preparation for the chosen profession according to the statements of current students.
MOŽNOSTI ROZVOJA REFLEXÍVNYCH KOMPETENCIÍ ŠTUDENTOV UČITEĽSTVA
Authors:   Pavol Jozef Šafárik University in Košice, Orosová Renáta , Starosta Volodymyr ,   Pavol Jozef Šafárik University in Košice
Published: September 2024

DEVELOPMENT POSSIBILITIES OF REFLECTIVE SKILLS IN TEACHER EDUCATION STUDENTS The study focuses on the potential for developing reflective competencies in future teachers through simulation strategies. Reflective competencies are crucial for the professional growth of teachers, as they enable them to critically assess their own teaching practices and adapt them to the dynamic needs of students. The research involved 68 student teachers, who were evaluated by 102 mentor teachers before and after the application of simulation strategies (video reflection, reflective discussion, selfreflection). The Wilcoxon Signed-Rank Test was used to compare the levels of reflective competencies before and after the intervention. The results showed that the p-value was significantly lower than the threshold of 0.05, indicating a statistically significant difference between the pretest and posttest. The findings suggest that simulation strategies had a positive impact on the development of students' reflective competencies. The average ratings increased significantly after the intervention, confirming the effectiveness of simulation strategies as an educational tool. Based on these results, it is recommended to implement simulation strategies in teacher education programs to enhance the preparation of future teachers for their professional practice.
An example of the application of artificial intelligence models in human resources processes
Authors: Sürücü Selim , Küçük Berk , Aydın Mustafa Kemal
Published: September 2024

Creating job postings and selecting suitable candidates among these job postings is a challenging process. This process increases the workload of human resources and causes the process to proceed slowly. It is of great importance for human resources departments to utilize information processing technologies to create job postings effectively and to evaluate the CVs of applicants to these postings. This study introduces and analyzes two different technologies that can help human resources. In the process of preparing job advertisements in the field of IT, in the first stage, the word cloud method is used to decide which keywords should be emphasized in the advertisement texts. In the second stage, the resumes of the applicants are analyzed using three different deep learning models such as CNN (Convolutional Neural Network), GRU (Gated Recurrent Unit), and LSTM (Long Short-Term Memory) for classification purposes. While the performance of these models is evaluated using metrics such as accuracy, MCC, F_1 score, and MSE, the decision-making processes of the models with explainable artificial intelligence are also analyzed. In this context, the GRU model, which achieved an accuracy of 99%, provided the most superior result in this study and the literature. This research shows that deep learning models provide high accuracy rates and efficiency in human resources resume classification and candidate matching processes. It also explains that using the word cloud method, the most appropriate keywords can be identified, and advertisements can be created.
Erfarenheter av att komplettera undervisningen med generativ AI
Authors: Törnered Karl
Published: September 2024

I denna artikel utforskar jag integrationen av artificiell intelligens (AI) i min undervisning inom naturvetenskap och teknik med TPACK-modellen som reflektionsram. Utifrån min erfarenhet som lärare diskuterar jag bland annat möjligheterna att använda AI-verktyg för att skapa alternativa provversioner och fysiksimuleringar. Artikeln belyser både möjligheter och utmaningar med AI i undervisningen och betonar vikten av att kombinera AI med traditionella pedagogiska metoder. Genom att tillämpa TPACK-modellen diskuterar jag hur teknisk, pedagogisk och ämnesmässig kompetens samspelar vid AI-integration i undervisningen. Avslutningsvis rekommenderas lärare att kritiskt utforska AI:s potential i STEM-undervisning.
A Matemática na Educação Infantil
Authors: Celestino Mafra Bianca , Negrão Felipe da Costa , Nascimento de Andrade Alexandra
Published: September 2024

O presente estudo, de abordagem qualitativa e de cunho descritivo, teve o objetivo de analisar como as noções matemáticas são apresentadas no Currículo Escolar Municipal de Manaus (CEMM) para as crianças da Educação Infantil (creche e pré-escola), mediante uma análise documental. Os resultados apontam as seguintes noções matemáticas presentes no documento: números, quantidades e sequência numérica/regularidade numérica; contagem, registro e notação numérica; resolução de problemas matemáticos cotidianos; formas geométricas; cores; noções/relações espaciais; noção de direção; tamanho, peso e espessura; noções sobre unidade de medidas e grandezas; e conceitos básicos de tempo. No entanto, nossas reflexões apontam para a importância de tornar explícitas essas ideias em todas os campos de experiência, uma vez que os conceitos matemáticos na Educação Infantil não devem ser tratados separadamente nem disciplinarmente, considerando as políticas públicas pertinentes, os debates teóricos e principalmente as crianças como sujeitos de direitos que constroem sua própria cultura.
A Geometria nos primeiros anos escolares sob o olhar dos Registros de Diários de Classe
Authors: Guedes Caetano Marcos Antônio , Kaiber Carmen Teresa
Published: September 2024

Este texto tem por objetivo caracterizar os saberes geométricos ensinados nos Anos Iniciais a partir de registros nos diários de classe em aulas de Matemática de unidades de ensino que integram a rede pública do município de Caravelas, interior da Bahia. Adota como marco cronológico o período de 2010 a 2019, em tempos de Parâmetros Curriculares Nacionais e da Base Nacional Comum Curricular. O estudo de abordagem qualitativa de procedimento documental que lança mão de 92 diários de classe tomados como fonte de análise é um recorte de uma pesquisa de doutorado em andamento, a qual tem como problema de pesquisa: Quais são os vestígios do ensino de Geometria contemplados nos primeiros anos escolares no município de Caravelas, levando em consideração a importância desta abordagem na formação discente? Para tanto, apoia-se em referenciais teóricos que utilizam os documentos escolares como fontes de investigação no âmbito da educação matemática e nos pressupostos da análise textual discursiva como ferramenta analítica. Os resultados mostram que a unidade temática de Geometria vem sendo inserida gradativamente nas práticas pedagógicas dos anos iniciais, com abordagens sobre figuras planas e espaciais, localização espacial, ângulos, simetria, polígonos, entre outras. Nesse contexto, o livro didático que vem se adequando às diretrizes curriculares vigentes, aparece como instrumento de apoio ao trabalho docente, contribuindo para esta inserção.
Letramento Estatístico
Authors: Aymoré Ferrandin Laura Carolina , Rolkouski Emerson
Published: September 2024

Este estudo analisa os níveis de letramento estatístico, propostos pela BNCC e pelos planos de aula disponibilizados em uma plataforma digital. O objetivo é comparar a progressão do letramento estatístico ao longo dos anos escolares, buscando comparar o nível proposto pela BNCC e o que é fornecido pelos planos de aula. Com esse fim, propõem-se desdobramentos dos níveis de letramento estatístico propostos e, à luz da Análise Textual Discursiva, catalogar e identificar qual o nível de letramento estatístico para cada ano escolar, para a BNCC e para os planos de aula. Com esse estudo, conclui-se que os planos de aula estão, em geral, alinhados com a BNCC, porém, ao olhar individualmente para cada desdobramento, não se obtém o mesmo resultado, contendo divergências no que se espera da compreensão gráfica e tabular.
Articulação entre Sequências Recursivas e teoria dos Grupos Finitos
Authors: Teófilo de Sousa Renata , Vieira Renata Passos Machado , Alves Francisco Régis Vieira , Aires Ana Paula Florêncio , Catarino Paula Maria Machado Cruz
Published: September 2024

Este artigo tem como objetivo apresentar uma abordagem para explorar a sequência de Padovan de forma articulada à teoria dos grupos finitos, no contexto do ensino de matemática. Para isso, adota-se como metodologia de pesquisa a Engenharia Didática, em suas duas primeiras fases –análises preliminares e concepção e análise a priori –, de modo combinado à Teoria das Situações Didáticas, para a composição de um modelo de ensino. Utiliza-se como suporte o software GeoGebra, em que se relaciona a sequência de Padovan, que é uma sequência infinita, aos grupos finitos a partir da congruência modular, reescrevendo-a como sequência finita. A partir da construção no GeoGebra e sua análise, foram identificados padrões cíclicos na sequência de Padovan módulo m e discute-se como esses padrões podem ser explorados didaticamente, propondo atividades práticas e mediações específicas para o ensino de conceitos de grupos finitos em sala de aula.
Projetos Pedagógicos dos Cursos de Licenciatura em Matemática da UFPA
Authors: Cantão Raissa de Sousa , Gonçalves Raquel Pinto , Lima Reinaldo Feio , Gontijo Cleyton Hércules
Published: September 2024

Esta investigação configura-se como pesquisa documental cujo objetivo é identificar e compreender como é organizada a formação matemática dos cursos da Universidade Federal do Pará (UFPA), do ponto de vista Educação Especial, na perspectiva inclusiva. Para a produção dos dados, optamos pelas informações contidas em oito Projetos Pedagógicos de Curso (PPC) de Licenciatura em Matemática da UFPA, ofertadas nos campi Belém, do Instituto de Educação Matemática e Científica (BELÉM/IEMCI),e do Instituto de Ciências Exatas e Naturais (BELÉM/ICEN); dos campi de Abaetetuba; Bragança; Breves; Cametá; Castanhal e Salinópolis. Os resultados preliminares apontam que a maioria dos campi oferecem mais do que a disciplina Libras; no entanto, há necessidade de ampliar os espaços formativos, com vistas a garantir aos futuros professores um conjunto de conhecimentos e competências para desenvolver um trabalho pedagógico inclusivo no campo da Matemática.
Conhecendo a Natureza
Authors: Staffa da Costa João Francisco , Do Rosário Lima Valderez Marina , Machado Pompeu Marcela
Published: September 2024

No presente artigo objetiva-se relatar uma experiência didática que utilizou como pressuposto teórico-metodológico a Pesquisa em Sala de Aula. As atividades foram desenvolvidas em um componente curricular denominado Iniciação Científica, com a participação de 25estudantes do 4º ano do Ensino Fundamental de uma escola pública municipal, localizada no estado do Rio Grande do Sul. Apresentaram-se as etapas de desenvolvimento da Pesquisa em Sala de Aula, detalhamento das atividades realizadas pelos participantes, discussão de pontos considerados essenciais e as considerações finais. Conclui-se que a Pesquisa em Sala de Aula é uma das formas de organização do trabalho pedagógico que pode contribuir para que os estudantes atinjam novo patamar de conhecimento sobre um determinado assunto, em particular, a natureza.
Música e silêncio
Authors: Brelet Gisèle , Bonin Gustavo , Di Fiori Pondian Juliana
Published: September 2024

A música precisa do silêncio para tornar-se uma presença para aqueles que a experenciam; silêncio originário que a envolve e do qual ela nasce, morre e renasce em uma contínua atividade do espírito. Como símbolo das possibilidades sonoras virtuais e da liberdade construtiva e destrutiva do ser, o silêncio produz a espera vivida na duração musical, expectativa que é atenção à forma musical e participação do ato que a engendra. Não sendo apenas ausência de som, é a ele que nos dirigimos intimamente para encontrar a completude da forma musical, seja nas suas conclusões, seja nas suas cessações inconclusas. Qualquer que seja a sua qualidade afetiva, suas forças expressivas ou formais, o silêncio contém um chamado para a sua superação, para o ato do espírito que o ultrapassa. E a música, fruto das qualidades subjetivas do silêncio, deve sempre retornar a ele para alcançar sua completude.
Content analysis of conversations on Reddit: reactions to FDA’s ENDS prioritized enforcement policy
Authors: Guillory Jamie , Trigger Sarah , Brophy Jenna , Ross Ashley , Lane Stephanie , Kim Annice , Nonnemaker James , Liu Sherry T. , Snyder Kimberly , Delahanty Janine
Published: September 2024

Introduction

On January 2, 2020, the FDA announced a policy focused in part on prioritizing enforcement of flavored (other than tobacco- or menthol-flavored) cartridge-based electronic nicotine delivery systems (ENDS) without premarket authorization.

Methods

We used a query to identify Reddit conversations relevant to the policy from January 2 to May 6, 2020. Our sample included 576 posts (46 posts and 530 accompanying comments). Two analysts coded posts for mentions of use behaviors (e.g., switching, quitting), purchasing behaviors (e.g., purchasing from retailer new to the user), and flavored products. We summarized frequencies of coded data and provided illustrative quotes.

Results

Only 21.0% (121/576) of posts mentioned use behavior. Switching behavior was the most common use behavior mentioned (50.4%, 61/121). Most switching behavior posts focused on ENDS-related switching (91.8%, 56/61). The most common ENDS-related switching behaviors mentioned were switching to an open tank (45.9%, 28/61) or device with refillable pods/cartridges (44.3%, 27/61); 8.2% (5/61) mentioned switching to disposables. Just 15.5% (89/576) of posts mentioned purchasing behavior, with the most common being purchasing from a retailer new to the user (32.6%, 29/89). Only 6.8% (39/576) of posts mentioned specific flavors.

Conclusion

Reddit posts about the policy commonly discussed switching to non-cartridge-based ENDS products, such as open tank systems or disposable devices, and purchasing products from different online sources that were still selling these products. Findings suggest that publicly available Reddit data can complement data from traditional sources (e.g., surveys, sales) to understand potential unintended consequences associated with policies by exploring the public’s reactions.
RE-ARMing salt marshes: a resilience-experimentalist approach to prescribed fire and bird conservation in high marshes of the Gulf of Mexico
Authors: Stantial Michelle L. , Fournier Auriel M. V. , Lawson Abigail J. , Marcot Bruce G. , Woodrey Mark S. , Lyons James E.
Published: September 2024

Uncertainty, complexity, and dynamic changes present challenges for conservation and natural resource management. Evidence-based approaches grounded in reliable information and rigorous analysis can enhance the navigation of the uncertainties and trade-offs inherent in conservation problems. This study highlights the importance of collaborative efforts and evidence-based decision-making, specifically implementing the Resilience-Experimentalist school of adaptive management (RE-ARM), which emphasizes stakeholder involvement, shared understanding, and experimentation. Our goal was to develop an adaptive management framework to reduce the uncertainty around the use of prescribed fire to manage the habitat for eastern black rails (Laterallus jamaicensis jamaicensis) and mottled ducks (Anas fulvigula) in saltmarshes of the Gulf of Mexico. Supported by discussions at a series of workshops, we used a value of information analysis to select a fire management hypothesis to test, developed an influence diagram to represent the system under fire management, used the influence diagram to develop a Bayesian decision network (BDN), and conducted a power analysis to guide management experiments and monitoring. Value of information analysis identified fire return interval as the critical uncertainty. Our BDN provided valuable insight into how managers believe prescribed fire influences vegetation characteristics and how vegetation influences both eastern black rail occupancy and mottled duck abundance. The results of the power analysis indicated that a standard occupancy modeling framework was more useful to compare 2- and 5-year fire return intervals for black rails than two alternative designs (removal and conditional). Our BDN can be used to predict the probability of achieving the desirable vegetative response to increase the occupancy probability of black rails and abundance of mottled ducks, and monitoring data can be used to update the BDN (learn) and improve best management practices for prescribed burns (adapt). Linking the value of information, BDNs, and power analysis enhances our understanding of the system, improves management decision-making, and builds trust among scientists, interested parties, and decision-makers. This approach lays the groundwork for knowledge co-production and adaptive management.
Regulation techniques and applications of distributed load resources in urban power grids based on internet of things
Authors: Zhou Quan , Wu Jiajia , Yin Yongliang
Published: September 2024

The power consumption of urban power systems is increasing rapidly with two typical trends: the first one is that the daily peak-valley difference of loads is more significant, and the power supply is tight during peak hours, which threatens the system’s safe and stable operation; the second one is that the load energy efficiency in urban power systems is not high, which is the primary source of carbon emission in the power industry. Therefore, reducing the peak power and improving the system’s energy efficiency are urgent tasks for enhancing the system’s security and achieving the carbon emission goals. The rapid development of the Internet of Things (IoTs) ushers new opportunities for regulating demand-side loads. By analyzing the technical characteristics of load control based on IoTs, this paper investigates the modeling methods of load resources. On this basis, different control and optimization methods of load resources are analyzed and compared thoroughly. Besides, considering that load control is not only related to technical methods but also impacted by incentive strategies, the load control mechanisms under the mature and immature market environments are analyzed. Finally, the research gap and prospect of load regulation are proposed.
Screening of genes co-associated with osteoporosis and chronic HBV infection based on bioinformatics analysis and machine learning
Authors: Yang Jia , Yang Weiguang , Hu Yue , Tong Linjian , Liu Rui , Liu Lice , Jiang Bei , Sun Zhiming
Published: September 2024

Objective

To identify HBV-related genes (HRGs) implicated in osteoporosis (OP) pathogenesis and develop a diagnostic model for early OP detection in chronic HBV infection (CBI) patients.

Methods

Five public sequencing datasets were collected from the GEO database. Gene differential expression and LASSO analyses identified genes linked to OP and CBI. Machine learning algorithms (random forests, support vector machines, and gradient boosting machines) further filtered these genes. The best diagnostic model was chosen based on accuracy and Kappa values. A nomogram model based on HRGs was constructed and assessed for reliability. OP patients were divided into two chronic HBV-related clusters using non-negative matrix factorization. Differential gene expression analysis, Gene Ontology, and KEGG enrichment analyses explored the roles of these genes in OP progression, using ssGSEA and GSVA. Differences in immune cell infiltration between clusters and the correlation between HRGs and immune cells were examined using ssGSEA and the Pearson method.

Results

Differential gene expression analysis of CBI and combined OP dataset identified 822 and 776 differentially expressed genes, respectively, with 43 genes intersecting. Following LASSO analysis and various machine learning recursive feature elimination algorithms, 16 HRGs were identified. The support vector machine emerged as the best predictive model based on accuracy and Kappa values, with AUC values of 0.92, 0.83, 0.74, and 0.7 for the training set, validation set, GSE7429, and GSE7158, respectively. The nomogram model exhibited AUC values of 0.91, 0.79, and 0.68 in the training set, GSE7429, and GSE7158, respectively. Non-negative matrix factorization divided OP patients into two clusters, revealing statistically significant differences in 11 types of immune cell infiltration between clusters. Finally, intersecting the HRGs obtained from LASSO analysis with the HRGs identified three genes.

Conclusion

This study successfully identified HRGs and developed an efficient diagnostic model based on HRGs, demonstrating high accuracy and strong predictive performance across multiple datasets. This research not only offers new insights into the complex relationship between OP and CBI but also establishes a foundation for the development of early diagnostic and personalized treatment strategies for chronic HBV-related OP.
Case report: Recurrence of primary hepatic neuroendocrine tumors after resection of liver segments IV in 8 years follow-up
Authors: Li Chunli , Bian Li , Fan Guangtao , Huang Yilong , Li Jiang , He Bo
Published: September 2024

Background

Primary hepatic neuroendocrine tumors (PHNETs) are an utterly rare entity. The diagnosis of PHNETs could legitimize when an extrahepatic primary NET must always be excluded. PHNETs can achieve a high survival rate after complete surgical resection, however, most patients still have an 18% risk of recurrence within 5 years after surgery. In our case, the recurrence occurred 8 years after the first hepatectomy, which is relatively rare in the current literature. Therefore, rigorous postoperative follow-up is necessary for early detection and timely treatment of recurrent PHNETs.

Case information

We report a case of PHNET in a 24-year-old previously healthy female patient who relapsed 8 years after hepatectomy. This case focuses on the importance of diagnosis of primary and recurrent PHNETS in young patients, rare pathological types, and post-operative follow-up.

Conclusion

This case report detailed the rare pathological morphology and characteristic immunohistochemical markers in our case for PHNETS, which enhanced the new understanding of the diagnosis of this entity. In addition, we also highlighted the variable duration of recurrence after treatment of PHNETs. The 8-year recurrent period in our case suggests the importance of regular examination in patients with PHNETs by following the doctor’s instructions.
The composition of the stent microbiome is associated with morbidity and adverse events during endoscopic drainage therapy of pancreatic necroses and pseudocysts
Authors: Frost Fabian , Khaimov Valeria , Senz Volkmar , Weiss Stefan , Klußmann-Fricke Bastian , Rühlemann Malte , Bang Corinna , Franke Andre , Pickartz Tilman , Budde Christoph , Aghdassi Ali A. , Siewert Stefan , Weiss Frank U. , Grabow Niels , Lerch Markus M. , Sendler Matthias
Published: September 2024

Background

Development of pancreatic necroses or pseudocysts are typical complications of pancreatitis and may require endoscopic drainage therapy using metal or plastic stents. Microbial infection of these lesions poses a major challenge. So far, the composition and significance of the microbial colonization on drainage stents are largely unknown although it may impact outcomes during endoscopic drainage therapy.

Methods

A total of 26 stents used for drainage of pancreatic lesions were retrieved and the stent microbiome was determined by 16S rRNA gene sequencing. Additional analysis included comparison of the stent microbiome to the intracavitary necrosis microbiome as well as scanning electron microscopy (SEM) and micro-computed tomography (μCT) imaging of selected metal or plastic stents.

Results

The stent microbiome comprises a large proportion of opportunistic enteric pathogens such as Enterococcus (14.4%) or Escherichia (6.1%) as well as oral bacteria like Streptococcus (13.1%). Increased levels of opportunistic enteric pathogens were associated with a prolonged hospital stay (r = 0.77, p = 3e−06) and the occurrence of adverse events during drainage therapy (p = 0.011). Higher levels of oral bacteria were associated (r = −0.62, p = 8e-04) with shorter durations of inpatient treatment. SEM and μCT investigations revealed complex biofilm networks on the stent surface.

Conclusion

The composition of the stent microbiome is associated with prolonged hospital stays and adverse events during endoscopic drainage therapy, highlighting the need for effective infection control to improve patient outcomes. In addition to systemic antibiotic therapy, antimicrobial stent coatings could be a conceivable option to influence the stent microbiome and possibly enhance control of the necrotic microflora.
The synergistic effects of anoikis-related genes and EMT-related genes in the prognostic prediction of Wilms tumor
Authors: Meng Kexin , Zhao Zerui , Gao Yaqing , Wu Keliang , Liu Wei , Wang Xiaoqing , Zheng Yi , Zhao Wei , Wang Bei
Published: September 2024

Wilms tumor (WT) is the most common type of malignant abdominal tumor in children; it exhibits a high degree of malignancy, grow rapidly, and is prone to metastasis. This study aimed to construct a prognosis model based on anoikis-related genes (ARGs) and epithelial-mesenchymal transition (EMT)-related genes (ERGs) for WT patients; we assessed the characteristics of the tumor microenvironment and treatment efficacy, as well as identifying potential therapeutic targets. To this end, we downloaded transcriptome sequencing data and clinical data for WT and normal renal cortices and used R to construct and validate the prognostic model based on ARGs and ERGs. Additionally, we performed clinical feature analysis, nomogram construction, mutation analysis, drug sensitivity analysis, Connectivity Map (cMAP) analysis, functional enrichment analysis, and immune infiltration analysis. Finally, we screened the hub gene using the STRING database and validated it via experiments. In this way, we constructed a model with good accuracy and robustness, which was composed of seven anoikis- and EMT-related genes. Paclitaxel and mesna were selected as potential chemotherapeutic drugs and adjuvant chemotherapeutic drugs for the WT high-risk group by using the Genomics of Drug Sensitivity in Cancer (GDSC) and cMAP compound libraries, respectively. We proved the existence of a strong correlation between invasive immune cells and prognostic genes and risk scores. Next, we selected NTRK2 as the hub gene, and in vitro experiments confirmed that its inhibition can significantly inhibit the proliferation and migration of tumor cells and promote late apoptosis. In summary, we screened out the potential biomarkers and chemotherapeutic drugs that can improve the prognosis of patients with WT.
Transfer learning approach in pre-treatment CT images to predict therapeutic response in advanced malignant pleural mesothelioma
Authors: Fanizzi Annarita , Catino Annamaria , Bove Samantha , Comes Maria Colomba , Montrone Michele , Sicolo Angela , Signorile Rahel , Perrotti Pia , Pizzutilo Pamela , Galetta Domenico , Massafra Raffaella
Published: September 2024

Introduction

Malignant pleural mesothelioma (MPM) is a poor-prognosis disease. Owing to the recent availability of new therapeutic options, there is a need to better assess prognosis. The initial clinical response could represent a useful parameter.

Methods

We proposed a transfer learning approach to predict an initial treatment response starting from baseline CT scans of patients with advanced/unresectable MPM undergoing first-line systemic therapy. The therapeutic response has been assessed according to the mRECIST criteria by CT scan at baseline and after two to three treatment cycles. We used three slices of baseline CT scan as input to the pre-trained convolutional neural network as a radiomic feature extractor. We identified a feature subset through a double feature selection procedure to train a binary SVM classifier to discriminate responders (partial response) from non-responders (stable or disease progression).

Results

The performance of the prediction classifiers was evaluated with an 80:20 hold-out validation scheme. We have evaluated how the developed model was robust to variations in the slices selected by the radiologist. In our dataset, 25 patients showed an initial partial response, whereas 13 patients showed progressive or stable disease. On the independent test, the proposed model achieved a median AUC and accuracy of 86.67% and 87.50%, respectively.

Conclusions

The proposed model has shown high performance even by varying the reference slices. Novel tools could help to improve the prognostic assessment of patients with MPM and to better identify subgroups of patients with different therapeutic responsiveness.
Transcriptome meta-analysis of Kawasaki disease in humans and mice
Authors: Gu Wanjun , Mirsaidi-Madjdabadi Sarah , Ramirez Francisco , Simonson Tatum S. , Makino Ayako
Published: September 2024

Kawasaki Disease (KD) affects young children less than five years old with severe blood vessel inflammation. Despite being treatable, the causes and mechanisms remain elusive. This study conducted a meta-analysis of RNA sequencing (RNA-seq) data from human and animal models to explore KD's transcriptomic profile and evaluate animal models. We retrieved bulk and single-cell RNA-seq data from Gene Expression Omnibus, with blood and coronary artery samples from KD patients, aorta samples from KD mouse models (Lactobacillus casei cell wall extract-injected mice), and their controls. Upon consistent quality control, we applied Fisher's exact test to assess differential gene expression, followed by an enrichment analysis of overlapping genes. These studies identified 400 differentially expressed genes in blood samples of KD patients compared to controls and 413 genes in coronary artery samples. The data from KD blood and KD coronary artery samples shared only 16 differentially expressed genes. Eighty-one genes overlapped between KD human coronary arteries and KD mouse aortas, and 67 of these 81 genes were regulated in parallel in both humans and mice: 30 genes were up-regulated, and 37 were down-regulated. These included previously identified KD-upregulated genes: CD74, SFRP4, ITGA4, and IKZF1. Gene enrichment analysis revealed significant alterations in the cardiomyopathy pathway. Single-cell RNAseq showed a few significant markers, with known KD markers like S100A9, S100A8, CD74, CD14, IFITM2, and IFITM3, being overexpressed in KD cohorts. Gene profiles obtained from KD human coronary artery are more compatible with data from aorta samples of KD mice than blood samples of KD humans, validating KD animal models for identifying therapeutic targets. Although blood samples can be utilized to discover novel biomarkers, more comprehensive single-cell sequencing is required to detail gene expression in different blood cell populations. This study identifies critical genes from human and mouse tissues to help develop new treatment strategies for KD.
Bushen Huoxue formula attenuates lipid accumulation evoking excessive autophagy in premature ovarian insufficiency rats and palmitic acid-challenged KGN cells by modulating lipid metabolism
Authors: Li Tian , Wei Yao , Jiao Beibie , Hao Rui , Zhou Beibei , Bian Xinlan , Wang Peijuan , Zhou Yahong , Sun Xia , Zhang Jian
Published: September 2024

Introduction

Premature ovarian insufficiency (POI) has affected about 3.7% of women of reproductive age and is a major factor contributing to infertility. Bushen Huoxue formula (BHF), a traditional Chinese medicine prescription, is clinically used to treat POI in China. This study aims to investigate the potential mechanisms of BHF in combating POI using corticosterone-induced rats and palmitic acid (PA)-challenged human ovarian granulosa cells (GCs).

Methods

Initially, ultra performance liquid chromatography tandem mass spectrometry was employed to analyze the components of BHF. The pharmacodynamic parameters evaluated included body weight, ovaries index, and serum hormone in rats. Follicle numbers were observed using H&E staining. Additionally, PCNA and TUNEL staining were used to assess GCs proliferation and apoptosis, respectively. Lipid accumulation and ROS levels were examined using Oil Red O and ROS staining. Protein expressions were determined by western blot. To probe mechanisms, cell viability and E2 levels in BHF-treated, PA-stimulated GCs were determined using MTT and ELISA, respectively. Cell apoptosis and ROS levels were assessed using TUNEL and ROS staining. Proteins related to lipid metabolism and autophagy in PA-stimulated GCs were studied using agonists.

Results

Our results shown that BHF effectively normalized serum hormone levels, including follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), estradiol (E2), and luteinizing hormone (LH). Concurrently, BHF also significantly reduced follicular atresia and promoted cell proliferation while inhibiting apoptosis in POI rats. Furthermore, BHF mitigated ovarian lipid accumulation by modulating lipid metabolism, which included reducing lipid synthesis (expression of peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein α), increasing lipid catabolism (expression of adipose triglyceride lipase), and enhancing lipid oxidation (expression of carnitine palmitoyl transferase 1A). Mechanistically, the therapeutic effects of BHF on POI were linked with alleviation of lipid deposition-induced reactive oxygen species (ROS) accumulation and excessive autophagy, corroborating the results in PA-challenged GCs. After treatment with elesclomol (a ROS inducer) and rapamycin (an autophagy inducer) in GCs, the effects of BHF were almost counteracted under model conditions.

Conclusion

These findings suggest that BHF alleviates the symptoms of POI by altering lipid metabolism and reducing lipid accumulation-induced ROS and autophagy, offering evidence for BHF’s efficacy in treating POI clinically.
Silibinin inhibits PM2.5-induced liver triglyceride accumulation through enhancing the function of mitochondrial Complexes I and II
Authors: Li Dexin , Zhang Jingxin , Jin Yuxin , Zhu Yaoxuan , Lu Xiaoqing , Huo Xinmei , Pan Chunshui , Zhong Lijun , Sun Kai , Yan Li , Yan Lulu , Huang Ping , Li Quan , Han Jing-Yan , Li Yin
Published: September 2024

Background

The standardized extract of milk thistle seeds, known as silibinin, has been utilized in herbal medicine for over two centuries, with the aim of safeguarding the liver against the deleterious effects of various toxic substances. However, the role of silibinin in Particulate Matter (PM2.5)-induced intrahepatic triglyceride accumulation remains unclear. This study seeks to investigate the impact of silibinin on PM2.5-induced intrahepatic triglyceride accumulation and elucidate potential underlying mechanisms.

Methods

A model of intrahepatic triglyceride accumulation was established in male C57BL/6J mice through intratracheal instillation of PM2.5, followed by assessment of liver weight, body weight, liver index, and measurements of intrahepatic triglycerides and cholesterol after treatment with silibinin capsules. Hep G2 cells were exposed to PM2.5 suspension to create an intracellular triglyceride accumulation model, and after treatment with silibinin, cell viability, intracellular triglycerides and cholesterol, fluorescence staining for Nile Red (lipid droplets), and DCFH-DA (Reactive Oxygen Species, ROS), as well as proteomics, real-time PCR, and mitochondrial function assays, were performed to investigate the mechanisms involved in reducing triglycerides.

Results

PM2.5 exposure leads to triglyceride accumulation, increased ROS production, elevated expression of inflammatory factors, decreased expression of antioxidant factors, and increased expression of downstream genes of aryl hydrocarbon receptor. Silibinin can partially or fully reverse these factors, thereby protecting cells and animal livers from PM2.5-induced damage. In vitro studies show that silibinin exerts its protective effects by preserving oxidative phosphorylation of mitochondrial complexes I and II, particularly significantly enhancing the function of mitochondrial complex II. Succinate dehydrogenase (mitochondrial complex II) is a direct target of silibinin, but silibinin A and B exhibit different affinities for different subunits of complex II.

Conclusion

Silibinin improved the accumulation of intrahepatic triglycerides induced by PM2.5, and this was, at least in part, explained by an enhancement of oxidative phosphorylation in mitochondrial Complexes I and II.
The identification of potent dual-target monopolar spindle 1 (MPS1) and histone deacetylase 8 (HDAC8) inhibitors through pharmacophore modeling, molecular docking, molecular dynamics simulations, and biological evaluation
Authors: Hua Huilian , Guan Lixia , Pan Bo , Gao Junyi , Geng Yifei , Niu Miao-Miao , Li Zhiqin , Li Jindong
Published: September 2024

Background

Overexpression of monopolar spindle 1 (MPS1) and histone deacetylase 8 (HDAC8) is associated with the proliferation of liver cancer cells, so simultaneous inhibition of both MPS1 and HDAC8 could offer a promising therapeutic approach for the treatment of liver cancer. Dual-targeted MPS1/HDAC8 inhibitors have not been reported.

Methods

A combined approach of pharmacophore modeling and molecular docking was used to identify potent dual-target inhibitors of MPS1 and HDAC8. Enzyme inhibition assays were performed to evaluate the optimal compound with the strongest inhibitory activity against MPS1 and HDAC8. The selectivity of MPH-5 for MPS1 and HDAC8 was assessed on a panel of 68 kinases and other histone deacetylases. Subsequently, molecular dynamics (MD) simulation verified the binding stability of the optimal compound to MPS1 and HDAC8. Ultimately, in vitro cellular assays and in vivo antitumor assays evaluated the antitumor efficacy of the most promising compound for the treatment of hepatocellular carcinoma.

Results

Six dual-target compounds (MPHs 1–6) of both MPS1 and HDAC8 were identified from the database using a combined virtual screening protocol. Notably, MPH-5 showed nanomolar inhibitory effect on both MPS1 (IC50 = 4.52 ± 0.21 nM) and HDAC8 (IC50 = 6.07 ± 0.37 nM). MD simulation indicated that MPH-5 stably binds to both MPS1 and HDAC8. Importantly, cellular assays revealed that MPH-5 exhibited significant antiproliferative activity against human liver cancer cells, especially HepG2 cells. Moreover, MPH-5 exhibited low toxicity and high efficacy against tumor cells, and it overcomes drug resistance to some extent. In addition, MPH-5 may exert its antitumor effects by downregulating MPS1-driven phosphorylation of histone H3 and upregulating HDAC8-mediated K62 acetylation of PKM2. Furthermore, MPH-5 showed potent inhibition of HepG2 xenograft tumor growth in mice with no apparent toxicity and presented favorable pharmacokinetics.

Conclusion

The study suggests that MPH-5 is a potent, selective, high-efficacy, and low-toxicity antitumor candidate for the treatment of hepatocellular carcinoma.
The overexpression of R-spondin 3 affects hair morphogenesis and hair development along with the formation and maturation of the hair follicle stem cells
Authors: Olczak Alicja , Pieczonka Tomasz D. , Ławicki Szymon , Łukaszyk Konrad , Pulawska-Czub Anna , Cambier Linda , Kobielak Krzysztof
Published: September 2024

Mice hair follicles (HFs) are a valuable model for studying various aspects of hair biology, including morphogenesis, development, and regeneration due to their easily observable phenotype and genetic manipulability. The initiation and progression of hair follicle morphogenesis, as well as the hair follicle cycle, are regulated by various signaling pathways, of which the main role is played by the Wingless-type MMTV integration site family (Wnt) and the Bone Morphogenic Protein (BMP). During the hair follicle cycle, the BMP pathway maintains hair follicle stem cells (HFSCs) in a dormant state while the Wnt pathway activates them for hair growth. Given the pivotal role of the Wnt pathway in hair biology and HFSCs regulation, we investigated the influence of the Wnt modulator - R-spondin 3 (Rspo3), in these processes. For this purpose, we developed a transgenic mice model with the overexpression of Rspo3 (Rspo3GOF) in the whole ectoderm and its derivatives, starting from early morphogenesis. Rspo3GOF mice exhibited a distinct phenotype with sparse hair and visible bald areas, caused by reduced proliferation and increased apoptosis of hair matrix progenitor cells, which resulted in a premature anagen-to-catagen transition with a shortened growth phase and decreased overall length of all hair types. In addition, Rspo3GOF promoted induction of auchene and awl, canonical Wnt-dependent hair type during morphogenesis, but the overall hair amount remained reduced. We also discovered a delay in the pre-bulge formation during morphogenesis and prolonged immaturity of the HFSC population in the bulge region postnatally, which further impaired proper hair regeneration throughout the mice’s lifespan. Our data supported that Rspo3 function observed in our model works in HFSCs’ formation of pre-bulge during morphogenesis via enhancing activation of the canonical Wnt pathway, whereas in contrast, in the postnatal immature bulge, activation of canonical Wnt signaling was attenuated. In vitro studies on keratinocytes revealed changes in proliferation, migration, and colony formation, highlighting the inhibitory effect of constitutive overexpression of Rspo3 on these cellular processes. Our research provides novel insights into the role of Rspo3 in the regulation of hair morphogenesis and development, along with the formation and maturation of the HFSCs, which affect hair regeneration.