bluuebunny/crossref_metadata_2025 huggingface dataset:
Darcilla e Sandra, artesãs de “horizontes sem tamanhos”
Authors: Pereira José Carlos
Published: January 2025

A indagação através da memória e da história oral pode atualizar o passado, revelar tempos, espaços, e experiências de pessoas socialmente marginalizadas, invisibilizadas. O objetivo deste trabalho é apresentar trajetórias da Ir. Darcilla e da Ir. Sandra, com ênfase na história da primeira, e apontar como suas ações individuais e coletivas contribuíram para a transformação do sentido da história para pessoas e grupos sociais, especialmente mulheres, flageladas pela negação de direitos. A metodologia da pesquisa baseia-se na história oral. Ir. Sandra atuou junto a esposas, irmãs e filhas de trabalhadores migrantes do Vale do Jequitinhonha-MG; Ir. Darcilla, com famílias de trabalhadores rurais sem-terra e imigrantes, no Norte e Nordeste do Brasil. Os resultados indicam que, apesar do caráter patriarcal de instituições que (re)produzem a discriminação e violência de gênero, etnia/raça e classe, ambas contribuíram para a construção de brechas e horizontes possíveis de geração de trabalho remunerado, formação de lideranças, e, sobretudo, de recuperação da autoestima por pessoas que saíram da condição de subalternos e sem história, para a de protagonistas.  Consideramos que o acionamento da memória, a partir do presente, permite (re)visitar o passado, buscar a gênese da realidade atual, interpretá-la e informar possibilidades para o futuro, recolocando no centro da história os sujeitos dela alijados.
O Museu de lembranças, uma história de massacre e superação: retalhos que a educação crítica pode (ou deve) costurar
Authors: Mansour Renata Nascimento y , Reis Maria Amélia Gomes de Sousa
Published: January 2025

Sewing together the sections of a tragedy in a minefield through memories that sustain the dignity of a people in their historical experiences of struggle for survival is the objective of this scientific work that combines Museology, Heritage and Education. It is about bringing to light methodologies capable of building identity consciousness stablished on emancipatory educational processes, based on the heritage present in the “Museum of Memories” of Shatila, a Palestinian refugee camp (Lebanon), after the Sabra and Shatila massacre, in 1982. We strive to highlight relevant aspects in this “museum” under construction: the Palestinian tragedy, the set of feelings and emotions translated in relation to the memory objects exposed by refugees, the differentiated spaces of struggles for the production of interdisciplinary ethnocultural knowledge that is linked to political conflicts present in the midst of a civilizing process common in other parts of the world.
Teresina, da Fundação à Edificação do Imaginário Desenvolvimentista
Authors: Silva Victor Marcelo Pires Gonçalves da
Published: January 2025

Este artigo tem por foco abordar o processo de transferência de Oeiras, antiga capital da província do Piauí, para Teresina que a partir de 1852 passa a ser a nova capital. Analisar os enfrentamentos políticos de José Antônio Saraiva, então presidente da Província do Piauí, idealizador e promotor da consumação do empreendimento de mudança. Indiciar representações de atraso e progresso implicadas nesse evento. E por último, problematizar algumas características sociais e econômicas do cenário teresinense desde sua fundação à virada do século XIX para o XX, considerando as amarras econômicas e o lento desenvolvimento em referência às demandas integradoras do capitalismo industrial.
Narrativas autobiográficas de crianças em escola rural de Mossoró/RN
Authors: Rodrigues Érica Renata Clemente , Souza Elizeu Clementino de
Published: January 2025

A comunicação discute questões relacionadas às narrativas e escritos autobiográficos de crianças de escola rural e objetiva analisar narrativas de estudantes do 4º/5º ano sobre a escola rural, com ênfase nas experiências do cotidiano da Escola Municipal Raimundo Galdino da Silva, localizada no Assentamento Cordão de Sombra II – zona rural da cidade de Mossoró/RN. A investigação justifica-se no contexto da necessária discussão e luta por uma educação pública de qualidade, mais especificamente para as diferentes comunidades rurais, considerando suas especificidades e modos de habitar os territórios rurais. No contexto da cidade pesquisada não há implementação de uma política para as escolas municipais rurais, orientadas a trabalharem na lógica urbanocêntrica. Entendemos o rural como um espaço diversificado, com suas singularidades que precisam ser respeitadas, garantindo modos implicados de vida da população nos territórios rurais. A pesquisa é de base qualitativa e se ancora em princípios da pesquisa (auto)biográfica, através das narrativas de crianças sobre sua vida, como se veem, como experienciam a escola e seus significados para sua vida, ao buscarmos compreender o que sentem, desejam ou não, a partir do repertório social que constroem nas interações sociais com seus pares. Nesse sentido, o esforço reflexivo das crianças torna suas narrativas um objeto de estudo precioso para o acesso às construções que elas fazem a respeito do que vivem na escola.
Questões agrárias: agricultura familiar, acesso à terra e produção para autoconsumo
Authors: Santos Leiliane Rosa de Jesus , Araújo Vanessa Marzano
Published: January 2025

A terra é o principal meio para manter o agricultor no campo e, consequentemente, viabilizar a prática da agricultura familiar que permite acesso aos alimentos em quantidade e qualidade para que eles possam se manter nesse espaço sem, necessariamente, possuir uma renda monetária de forma constante. Esse artigo analisa o acesso à terra e a produção de autoconsumo em um assentamento rural no município de Jequitinhonha, MG. A pesquisa iniciou-se com um estudo bibliográfico, na sequência ocorreu pesquisa de campo, entrevistando as cinquenta e sete  famílias assentadas. Os resultados mostraram que o povoamento da região se deu de forma expansiva e conflituosa. Conclui-se então que o acesso à terra foi fundamental para que as famílias produzissem alimentos saudáveis e variados, mas que devido à falta de água em algumas épocas do ano não conseguem produzir em grande quantidade, devendo se ajustar a venda dos excedentes na feira para compra de outros produtos.
Modelo clássico da cidade Hispano-America
Authors: F. Luz Estela Carreiro
Published: January 2025

This work addressesbasic aspects of the Spanish-American city. First the background of is exposed whenthe arrival of the Spaniards in America; secondly the process of foundation and territorial occupation,it explains; then the layout of the citiesisdescribed, which was made bywith a cord starting from the main square; Next, the foundation of some cities in Latin America is reviewed. Finally, it presents the origin of the main square and the provisions of the Laws of the Indies followed for the foundation of urban centers and cities. The objective is to expose the Spanish-American city model and identify the value of the square over time. The work, inserted in the urban and historical environment, describes,and interprets a built context, urban historical facts,and the prospective study, to rescue the collective memory.
Representações sociais, racismo e educação
Authors: Rodrigues Ruth Meyre M.
Published: January 2025

We intend to address, in this production, reflections on the reproduction of racist social representations in the educational field, the bases for identifying ideological mechanisms that produce and reproduce ethnic-racial inequalities. Based on the theoryof social representations formulated by Serge Moscovici and in dialogue with Historical and Dialectical Materialism, the aim is to interpret the power relations and the instruments that promote oppression and exclusion based on the racialization and hierarchization of society as mechanisms of perpetuation of privileges. In this way, we intend to address elements that obstruct an anti-racist education and reproduce segregating actions, highlighting the recent setbacks that marked the conduct of social policies of social and racial inclusion.
Dawn, Mortals and Immortals in the Aeneid
Authors: Cianciosi Stefano
Published: January 2025

In Homer, Aurora sometimes illuminates gods and men. In Virgilian Dawn scenes, however, the gods are never said to receive her light. Thematic reasons can explain why this is the case. But even the intellectual progress of the centuries that separated Virgil from the Homeric poems might have influenced his choice. Ancient Homeric scholarship questioned the plausibility of the gods’ need for sunlight, and Hellenistic and Roman poets who influenced Virgil had already omitted the immortals in these formulae. The depiction of the gods in the Aeneid could respond to numerous factors such as the mechanics of the poet’s technique as well as aesthetic, philosophical and scientific trends that left traces in the writings of ancient Homeric scholars and imitators. Considering all these factors allows for a more nuanced understanding of Virgil’s modus operandi and can bring us closer to the perspective of a Roman audience of his time.
Effect of variation of biobased phenolic resin content in natural rubber blend on rheological, thermal and tribological properties
Authors: Kujur Akish E , Goswami Sudipta
Published: January 2025

A biobased copolymer, phenol-cardanol-formaldehyde (PCF928), was prepared by condensation reaction between phenol, cardanol, and formaldehyde. The mixture (P) of phenol and cardanol (92:8 w/w) was mixed with formaldehyde (F) in the molar ratio of 1:0.8 (P:F), and using oxalic acid as a catalyst, the reaction was carried out. This resin (PCF928) was blended with natural rubber in various proportions (like 5, 10, 20, and 30 phr), and four samples were prepared that had the same amounts of C-black as filler and all other ingredients. These were vulcanized in the presence of hexamethylene tetramine and sulfur together. These samples were characterized by density, hardness, and crosslink density. The blends possess higher crosslink density, hardness, and density than that of the pure rubber compound. Mechanical properties of the blends were greater than those of the pure natural rubber (NR) compound. All the blend samples were found equally stable up to 400⁰C. Storage and loss modulus of the blends improved with an increase in PCF928 content when measured by varying the frequency at a constant temperature (125⁰C). Wear resistance of the blends increased with a simultaneous reduction in the coefficient of friction due to the increase in the resin content in them.
Developing active learning activities for didactic perfusion courses
Authors: Kim Catherine , Gerrits Ronald
Published: January 2025

Background

In the world of academia, traditional lecturing has been the most common pedagogical approach for centuries. However, it can create an environment for students to be passive learners in the classroom. Alternatively, active learning is a pedagogical approach intended to encourage students to engage with content in manners which have been associated with improved exam performance, final course grades, clinical reasoning skills, and critical thinking skills. Given that perfusion is inherently a profession where didactic information must be applied in practice, the implementation of active learning in didactic courses is worth considering. Although active learning is practiced in perfusion education through participation in simulations and clinical rotations, there are no easily identifiable active learning resources available to supplement didactic perfusion courses. In response, written active learning activities were specifically designed for didactic perfusion courses.

Methods

The activities were designed based on the format for guided inquiry worksheets, the incorporation of the learning cycle, and the implementation of process oriented guided inquiry learning (POGIL) strategies. Key concepts were identified, learning objectives were specified, and models (figures or tables of data) were created as targets of engagement and analysis. Following each model, questions and prompts are given to guide students through identifying, understanding, and exploring the concepts incorporated in the activity as well as opportunities to apply the newly gained knowledge and understanding.

Results

Ten active learning activities have been developed based on the methods summarized above.

Conclusion

While the purposes of this paper are to inform the perfusion community of active learning and to share guidelines on how to create active learning activities for didactic perfusion courses, the goals of the activities are to provide examples to perfusion educators and to guide students in understanding basic perfusion concepts in a clinically relevant manner. It is recommended that perfusion students complete these activities alongside their didactic perfusion courses.
Mapping the regional and remote specialised mental health workforce: Commentary on the AIHW data for 2022–2023
Authors: Looi Jeffrey CL , Allison Stephen , Bastiampillai Tarun , Kisely Steve
Published: January 2025

Objective

The Australian Institute of Health and Welfare publishes statistical indicator reports on the specialised mental health workforce. These include data for 2022–2023 on psychiatrists, mental health nurses, mental health occupational therapists, psychologists and mental health social workers. We provide a brief commentary on these reports, reflecting upon the implications of such changes for psychiatric practice and patient care.

Conclusions

Overall, there are fewer mental health workers with increasing distance from urban centres. There are insufficient rural psychiatrists with the NT and Queensland having higher rates per 100,000 in outer regional and remote areas. Psychologists and mental health nurses have the highest rates per 100,000 in rural areas. Though low in absolute rates per 100,000, mental health social workers are better distributed in rural compared to urban areas. Further data on public, private and non-governmental sector employment would be useful.
Sustainable sound absorption using shredded plastic particles: Adjusting low-frequency acoustic performance with particle size
Authors: Železnik Anže , Čurović Luka , Prezelj Jurij
Published: January 2025

This study investigates the sound absorption properties of shredded recycled plastic particles, with a focus on how particle size influences low-frequency acoustic performance. Given the growing environmental challenge posed by plastic waste, this research aims to repurpose such materials into effective, sustainable sound absorbers, contributing to both noise reduction and waste minimization efforts. The sound absorption coefficients and normalized surface impedances of different size fractions, ranging from 45 µm to 3 mm, were measured using the standard two-microphone impedance tube method in accordance with ISO 10534-2. The analysis revealed that smaller particle sizes significantly enhance low-frequency absorption, though at the expense of the maximum absorption coefficient across a broader frequency range. This trade-off underscores the importance of particle size in designing materials tailored to specific acoustic applications. Results indicate that optimal sound absorption shifts towards higher frequencies for larger particle sizes, while finer particles are more effective at lower frequencies. The ability to customize the acoustic properties of shredded plastic particles by selecting appropriate particle sizes is a key outcome of this study. Microscopic examination of the particles revealed a correlation between particle morphology and acoustic performance, with irregular shapes contributing to enhanced sound energy dissipation. The findings suggest that shredded recycled plastic particles are a viable and sustainable option for creating customizable sound-absorbing materials, particularly in applications where low-frequency noise reduction is critical. This research not only advances the understanding of acoustic performance in recycled materials but also supports broader sustainability goals by offering an innovative use for plastic waste in industrial and architectural noise control solutions. In conclusion, this study provides a foundation for the development of eco-friendly, effective sound-absorbing materials from recycled plastics, emphasizing the importance of particle size in achieving desired acoustic properties.
Ensifentrine in COPD patients taking long-acting bronchodilators: A pooled post-hoc analysis of the ENHANCE-1/2 studies
Authors: Dransfield Mark , Marchetti Nathaniel , Kalhan Ravi , Reyner Daniel , Dixon Amy L , Rheault Tara , Rickard Kathleen Ann , Anzueto Antonio
Published: January 2025

Background

The efficacy and safety of ensifentrine, a novel PDE3/PDE4 inhibitor, were previously evaluated in the ENHANCE-1 (NCT04535986) and ENHANCE-2 (NCT04542057) trials. Here, we present a pooled post-hoc subgroup analysis of patients according to background chronic obstructive pulmonary disease (COPD) maintenance medication regimens.

Objective

This analysis aimed to explore the efficacy and safety of ensifentrine in patients receiving long-acting muscarinic antagonists (LAMA) or long-acting beta-agonists with inhaled corticosteroids (LABA + ICS).

Methods

Eligible patients had moderate to severe COPD, were aged 40–80 years, and were symptomatic at randomization. Patients were randomized 5:3, receiving twice-daily ensifentrine 3 mg or placebo via standard jet nebulizer over 24 weeks.

Results

The pooled post-hoc analysis included 485 LAMA patients and 272 LABA + ICS patients. Ensifentrine showed lung function improvement over placebo at week 12, including average FEV1 AUC0–12 h in the LAMA (placebo-corrected least squares mean change from baseline [LSMC], 92 mL; 95% CI, 54, 131; p < 0.001) and LABA + ICS subgroups (LSMC, 74 mL; 95% CI, 27, 121; p = 0.002). Ensifentrine reduced the rate and risk of exacerbations in both LAMA (48% and 50%, respectively) and LABA + ICS (51% and 56%, respectively) subgroups. Ensifentrine-treated patients reported improvement in symptoms and quality of life over 24 weeks. The safety profile of ensifentrine in each subgroup was similar to the profile in the pooled modified intention-to-treat population.

Conclusions

Nebulized ensifentrine offers a novel non-steroidal anti-inflammatory and bronchodilator treatment added to existing LAMA or LABA + ICS treatment options in patients with moderate to severe, symptomatic COPD.
Omega-3 fatty acids: molecular weapons against chemoresistance in breast cancer
Authors: Marchio Vittoria , Augimeri Giuseppina , Morelli Catia , Vivacqua Adele , Giordano Cinzia , Catalano Stefania , Sisci Diego , Barone Ines , Bonofiglio Daniela
Published: January 2025

Breast cancer is the most commonly diagnosed type of cancer and the leading cause of cancer-related death in women worldwide. Highly targeted therapies have been developed for different subtypes of breast cancer, including hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, triple-negative breast cancer (TNBC) and metastatic breast cancer disease are primarily treated with chemotherapy, which improves disease-free and overall survival, but does not offer a curative solution for these aggressive forms of breast cancer. Moreover, the development of chemoresistance is a major cause of therapeutic failure in this neoplasia, leading to disease relapse and patient death. In addition, chemotherapy’s adverse side effects may substantially worsen health-related quality of life. Therefore, to improve the outcome of patients with breast cancer who are undergoing chemotherapy, several therapeutic options are under investigation, including the combination of chemotherapeutic drugs with natural compounds. Omega-3 (ω-3) polyunsaturated fatty acids (PUFAs), including docosahexaenoic and eicosapentaenoic acids, have drawn attention for their antitumoral properties and their preventive activities against chemotherapy-induced toxicities in breast cancer. A literature review was conducted on PubMed using keywords related to breast cancer, omega-3, chemoresistance, and chemotherapy. This review aims to provide an overview of the molecular mechanisms driving breast cancer chemoresistance, focusing on the role of ω-3 PUFAs in these recognized cellular paths and presenting current findings on the effects of ω-3 PUFAs combined with chemotherapeutic drugs in breast cancer management.
Crop protection by RNA interference: a review of recent approaches, current state of developments and use as of 2013
Authors: Germing Kirsten , Navarrete Cecilia Andrea Díaz , Schiermeyer Andreas , Hommen Udo , Zühl Luise , Eilebrecht Sebastian , Eilebrecht Elke
Published: January 2025

RNAi-based applications aim to inhibit the expression of specific essential genes in target organisms by uptake and processing of double-stranded RNA and subsequent degradation of target gene mRNA. While the research on RNAi-based pesticides was initially limited to endogenous applications (i.e., production of the dsRNA by the crop), the development of technologies for exogenous applications like RNAi sprays in particular has increased in recent years. Due to the assumed beneficial properties of RNA molecules, such as degradability or target specificity, RNAi technology receives increasing attention in the development of plant protection products, as evidenced by a steadily increasing number of publications. A horizon scan was conducted with a specific emphasis to identify and illustrate the current state of RNAi developments and applications in crop protection as well as their biomanufacturing readiness levels. In this study, more than 180 publications were evaluated. Furthermore, we identified 268 patent families on this topic. A large variety with regard to treated crops, targeted pest species and target gene functions as well as application types was observed. In total, RNAi applications for more than 30 different pest species were identified, most of which belonged to the insect orders Lepidoptera, Hemiptera and Coleoptera. In addition, applications targeting fungi and viruses were found. RNAi applications were identified to be an upcoming topic in crop protection and, therefore, are becoming increasingly relevant for environmental risk assessment, due to the high number of targeted pest species as well as the variety of novel application types. With this review, we inform future work aimed to develop further adequate concepts and methods for environmental risk assessment of RNAi-based applications.
Transcriptional time-course analysis during ash dieback infection revealed different responses in tolerant and susceptible Fraxinus excelsior genotypes
Authors: Chano Víctor , Ferrari Renata Callegari , Domínguez-Flores Tania , Shrestha Karuna , Fussi Barbara , Seidel Hannes , Gailing Oliver , Budde Katharina B.
Published: January 2025

Hymenoscyphus fraxineus, the causal agent of Ash Dieback (ADB), has been introduced to eastern Europe in the 1990s from where it spread causing decline in European ash populations. However, the genetic basis of the molecular response in tolerant and susceptible ash trees to this disease is still largely unknown. We performed RNA-sequencing to study the transcriptomic response to the disease in four ash genotypes (ADB-tolerant FAR3 and FS36, and ADB-susceptible UW1 and UW2), during a time-course of 7, 14, 21, and 28 days post-inoculation, including mock-inoculated trees as control samples for each sampling time point. The analysis yielded 395 and 500 Differentially Expressed Genes (DEGs) along the response for ADB-tolerant FAR3 and FS36, respectively, while ADB-susceptible UW1 and UW2 revealed 194 and 571 DEGs, respectively, with most DEGs found exclusively in just one of the genotypes. DEGs shared between tolerant genotypes FAR3 and FS36, included genes involved in the production of phytoalexins and other secondary metabolites with roles in plant defense. Moreover, we identified an earlier expression of genes involved in both pattern- and effector-triggered immunity (PTI and ETI) in ADB-tolerant genotypes, while in ADB-susceptible genotypes both responses were delayed (late response). Overall, these results revealed different transcriptomic expression patterns not only between ADB-tolerant and ADB-susceptible genotypes, but also within these two groups. This hints to individual responses in the natural tolerance to ADB, possibly revealing diversified strategies across ash genotypes.
Reticulocyte hemoglobin content: a new frontier in iron deficiency diagnostics for major surgical patients
Authors: Choorapoikayil Suma , Kotlyar Mischa J. , Kawohl Lisa , Pratz Paul P. , Mehic Denana , Kranke Peter , Rumpf Florian , Blum Lea V. , Kloka Jan A. , Zacharowski Kai , Neef Vanessa , Meybohm Patrick
Published: January 2025

Background

Iron deficiency (ID) is the most common nutritional deficiency among patients undergoing major surgery. Treatment of ID is straightforward, however implementing a comprehensive anemia management strategy within clinical routines is complex. Recently, reticulocyte hemoglobin content (Ret-He) has been evaluated as an early marker for ID diagnosis.

Method

In this retrospective study, 2,966 major surgical patients from two University Hospitals were screened for the presence of ID and the significance of Ret-He in diagnosis ID was evaluated in both non-anemic and anemic patients. According to hemoglobin, ferritin, and transferrin saturation concentrations patients were assigned to a Control group (no anemia, no ID), ID group (no anemia, ID), IDA group (anemia, ID) or Others group (anemia, no ID).

Results

In total, 2,760 patients were included in analysis: Control (n = 1500; 54.2%), IDA (n = 412; 14.9%), ID (n = 487; 17.6%), and Others (n = 370; 13.4%). Ret-He was significantly decreased in the IDA group compared to ID, Control and Others, respectively (p < 0.001). The ROC curve analysis revealed an AUC of 0.842 (95% CI (0.82–0.87)) at Ret-He cutoff 33.5 pg, by which IDA was discriminated with 69.7% (95% CI (65.3–74.0%)) sensitivity and 85.7% (95% CI (82.3-86.1%)) specificity. Of the 370 patients with anemia of unknown cause (Others group) 131 had Ret-He levels < 33.5 pg. In these patients, the median values for ferritin was 492.0 ng/ml (333.5; 818.5 ng/ml) and transferrin saturation 11.9% (18.0; 23.3%). Logistic regression identified significant predictors of ID, with each decrease in Hb and Ret-He associated with a 19.4% (OR = 0.806; p < 0.001) and 26% (OR = 0.740; p < 0.001) increase in the odds of ID, respectively.

Conclusion

This study highlights the potential of Ret-He as a promising alternative marker for diagnosing ID in patients undergoing major surgery, particularly in cases of elevated ferritin levels or non-anemic patients. Ret-He may serve as a valuable tool to prioritize patients for further iron status testing, especially when preoperative time is limited.
Application of artificial intelligence in nursing practice: a qualitative study of Jordanian nurses’ perspectives
Authors: Almagharbeh Wesam Taher , Alfanash Hazem AbdulKareem , Alnawafleh Khaldoon Aied , Alasmari Amal Ali , Alsaraireh Faris Abdelkarim , Dreidi Mutaz M. , Nashwan Abdulqadir J.
Published: January 2025

Background

Artificial Intelligence (AI) is increasingly applied in healthcare to boost productivity, reduce administrative workloads, and improve patient outcomes. In nursing, AI offers both opportunities and challenges. This study explores nurses’ perspectives on implementing AI in nursing practice within the context of Jordan, focusing on the perceived benefits and concerns related to its integration.

Method

A qualitative research approach was employed, involving semi-structured interviews with 25 nurses and 3 focus group discussions, each consisting of 7–8 participants. The data collected was coded and analyzed using thematic analysis to identify recurring patterns and key themes in the nurses’ views on AI.

Results

Three major themes emerged from the analysis: (1) AI as an efficiency tool – Nurses recognized AI’s ability to reduce administrative burdens and improve patient monitoring in real-time. (2) Ethical and practical concerns – Nurses raised issues regarding patient privacy, data security, and the fear that AI might replace human decision-making in care. (3) Lack of preparedness and training – There was a consensus on nurses’ inadequate training in AI tools, limiting their ability to integrate AI into their practice fully.

Conclusion

While AI is seen as a valuable tool to enhance nursing productivity, several challenges still need to be addressed, particularly regarding ethical concerns and insufficient training. To ensure AI complements nursing without compromising the human element, healthcare institutions must address these issues by implementing comprehensive training programs and establishing clear ethical guidelines.
Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) and mortality among survivors of liver cirrhosis: a prospective cohort study
Authors: Fotros Danial , Hekmatdoost Azita , Pashayee-khamene Fereshteh , Karimi Sara , Ahmadzadeh Saleheh , Saberifiroozi Mehdi , Hatami Behzad , Yari Zahra
Published: January 2025

Background

Cirrhosis is a medical condition marked by persistent liver damage, which leads to the development of fibrous tissue and compromised liver function. In the present study, we decided to investigate the possibility of a connection between the consumption of fermentable olig-, di-, monosaccharides, and polyols (FODMAPs) and mortality rates in cirrhotic patients by utilizing data obtained from a prospective cohort study.

Methods

This cohort study enrolled 166 ambulatory patients from two hospitals in Tehran, Iran, between 2016 and 2018, and followed them up for 5 48 months until April 30, 2022. During the 3,955 person-months of follow-up, 43 fatalities were recorded (36 men and 7 women). The study classified participants into three groups based on their FODMAPs consumption and assessed the risk of mortality using Cox proportional hazards regression models.

Results

Total FODMAPs intake was associated with increased overall mortality risk (T3 vs. T1, HR = 3.5; 95%CI: 1.05, 11.7; P-trend = 0.036). This significant trend was also observed for total fructans (T3 vs. T1, HR = 5.15; 95% CI: 1.15, 23.2; P-trend = 0.006) and fructose (T3 vs. T1, HR = 5.55; 95% CI: 0.54, 57.14; P-trend = 0.018). Mortality risk was U-shaped with galactooligosaccharide intake, a lower mortality risk was observed with lactose intake and a higher mortality risk with polyols intake, although these associations did not reach statistical significance.

Conclusion

In conclusion, this study highlights a higher risk of mortality with higher intake of fructans, excess fructose and total FODMAPs.
Association between the hemoglobin A1c/High-density lipoprotein cholesterol ratio and stroke incidence: a prospective nationwide cohort study in China
Authors: Huang Chaojuan , You Hongtao , Zhang Yuyang , Fan Ligang , Feng Xingliang , Shao Naiyuan
Published: January 2025

Background

Stroke has emerged as an escalating public health challenge among middle-aged and older individuals in China, closely linked to glycolipid metabolic abnormalities. The Hemoglobin A1c/High-Density Lipoprotein Cholesterol (HbA1c/HDL-C) ratio, an integrated marker of glycolipid homeostasis, may serve as a novel predictor of stroke risk.

Methods

Our investigation utilized data from the China Health and Retirement Longitudinal Study cohort (2011–2018). Stroke cases were identified based on self-reported, physician-confirmed diagnoses. Logistic regression models were established to determine the correlation between HbA1c/HDL-C and stroke prevalence (2011) as well as between cumulative mean HbA1c/HDL-C (2011–2015) and new stroke incidence (2015–2018). Additionally, smoothed curve fitting, subgroup analyses, and interaction tests were conducted to ensure the robustness of the findings.

Results

In the cross-sectional analysis, 8,502 participants were enrolled, of whom 189 had a history of stroke. Our findings revealed a significant positive linear relationship between HbA1c/HDL-C and stroke prevalence after adjusting for covariates (OR: 1.26, 95% CI: 1.09–1.45). When HbA1c/HDL-C was categorized into tertiles, only the highest tertile (T3) showed a significant correlation with stroke prevalence compared to the lowest tertile (T1) (OR:1.71, 95% CI: 1.05–2.77). In the longitudinal analysis of 5,165 participants, 336 cases of new-onset stroke were identified over a follow-up period of 7 years. Adjusting for confounders, individuals with higher cumulative mean HbA1c/HDL-C exhibited an increased likelihood of new stroke incidence (OR: 1.14, 95% CI: 1.01–1.29). Using the T1 of cumulative mean HbA1c/HDL-C as a reference, the fully adjusted OR for stroke was 1.65 (95% CI: 1.21–2.24) in T2 and 1.54 (95% CI: 1.08–2.19) in T3. The predictive value of the HbA1c/HDL-C in stroke risk assessment have been significantly improved compared to the traditional HDL-C and HbA1c. Consistent associations were observed across most stratified subgroups.

Conclusions

Elevated baseline and cumulative mean HbA1c/HDL-C levels are significantly associated with an increased risk of stroke among middle-aged and older individuals in China, underscoring the potential of HbA1c/HDL-C as a clinical marker for long-term stroke risk assessment and prevention strategies.
Association between triglyceride glucose index and adverse cardiovascular prognosis in patients with atrial fibrillation without diabetes: a retrospective cohort study
Authors: Gong Aobo , Cao Ying , Li Zexi , Li Wentao , Li Fanghui , Tong Yao , Hu Xianjin , Zeng Rui
Published: January 2025

Background

Atrial fibrillation (AF) is the most prevalent arrhythmia encountered in clinical practice. Triglyceride glucose index (Tyg), a convenient evaluation variable for insulin resistance, has shown associations with adverse cardiovascular outcomes. However, studies on the Tyg index’s predictive value for adverse prognosis in patients with AF without diabetes are lacking.

Methods

This retrospective study utilized electronic medical records to collect data on patients with AF hospitalized at West China Hospital from January to June 2020. Participants were categorized into three groups based on their Tyg index levels. The primary outcome, major adverse cardiovascular events, included cardiac death, stroke, and myocardial infarction. Kaplan–Meier curve, Cox proportional hazards regression model, and restricted cubic spline were employed to explore the relationship between the Tyg index and outcomes. The predictive performance of the CHA2DS2-VASc model was evaluated after incorporating the Tyg index.

Results

The study comprised 864 participants (mean age 67.69 years, 55.32% male, 57.52% paroxysmal AF). Patients with high Tyg index had a significantly higher risk of developing major adverse cardiovascular events (MACE) (P < 0.001, hazard ratio: 2.05, 95% confidence interval:1.65–2.56). The MACE risk in the middle Tyg group was similar to that in the low Tyg group (P = 0.1) during the 48-month follow-up period. However, focusing on the last 24 months revealed a higher MACE risk (P = 0.015) in the middle Tyg group. The restricted cubic spline analysis revealed an S-shaped correlation between Tyg and MACE. The CHA2DS2-VASc model combined with the Tyg index showed improved predictive performance and net benefit.

Conclusions

A high Tyg index is associated with poorer prognosis in patients with AF without diabetes. Integrating the Tyg index into the CHA2DS2-VASc model may enhance its predictive performance, offering clinical utility.
Multiple gene-deletion vaccinia virus Tiantan strain against mpox
Authors: Zhu Yilong , Li Dapeng , Zhao Renshuang , Chen Minghua , Li Yue , Yang Xia , Mao Hongyue , Li Xiao , Li Yiquan , Shang Chao , Xia Xianzhu
Published: January 2025

Monkeypox virus (MPXV) is an important zoonotic pathogenic virus, which poses serious threats to public health. MPXV infection can be prevented by immunization against the variola virus. Because of the safety risks and side effects of vaccination with live vaccinia virus (VACV) strain Tian Tan (VTT), we constructed two gene-deleted VTT recombinants (TTVAC7 and TTVC5). The immunogenicity and protective effects of the gene-deleted VTT vaccine were assessed using BALB/C mice challenged with VTT and New Zealand rabbits challenged with MPXV. The results demonstrated strong humoral and cellular immune responses. The VTT-specific and neutralizing antibody titers, specific T cell levels, and degree of dendritic cell maturation of the mice, in addition to the MPXV neutralizing antibody titers and IFN-γ, IL-6, and TNF-α levels of the rabbits were markedly higher in the groups immunized with TTVAC7 and TTVC5 than the control groups (p < 0.05). Moreover, immunization with TTVAC7 and TTVC5 reduced morbidities caused by VACV and MPXV infection. The weight change, lung histological score, and residual virus of the mouse model (p < 0.05). Similarly, the temperature change, pock number, lung histological score, and residual virus of the rabbit model were significantly reduced in the groups immunized with TTVAC7 and TTVC5 (p < 0.05). Collectively, these results demonstrate that TTVAC7 and TTVC5 may be used as potential live attenuated vaccines against MPXV infection.
LLT1 overexpression renders allogeneic-NK resistance and facilitates the generation of enhanced universal CAR-T cells
Authors: Zhu Shuxian , Zuo Shiyu , Li Chuo , You Xingjie , Jiang Erlie , Feng Xiaoming , Luo Yuechen
Published: January 2025

Background

The benefit of universal CAR-T cells over autologous CAR-T cell therapy is that they are a treatment that is ready to use. However, the prevention of graft-versus-host disease (GVHD) and host-versus-graft reaction (HVGR) remains challenging. Deleting class I of human leukocyte antigen (HLA-I) and class II of human leukocyte antigen (HLA-II) can prevent rejection by allogeneic T cells; however, natural killer (NK) cell rejection due to the loss of self-recognition remains unresolved. This study tested whether the overexpression of Lectin-like transcript 1 (LLT1), an NK cell inhibitory ligand, in T cell receptor (TCR) and HLA-I/II disrupted universal CD38-targeting CAR-T cells could prevent rejection by allogeneic NK cells.

Methods

We generated CD38-targeting universal CAR-T cells by transducing T cells with lentiviruses encoding the CD38 CAR and LLT1 constructs. T cells were subjected to CD38, TCR, HLA-I, and HLA-II gene knockdown using CRISPR/Cas9, followed by lentiviral transduction. We performed cytotoxicity, proliferation, and cytokine assays to evaluate the functionality of universal chimeric antigen receptor-T cell (UCAR-T) cells and conducted in vitro and in vivo assays, including allogeneic responses and RNA sequencing, to assess their resistance to allogeneic T and NK cells, anti-leukemia efficacy, and persistence in treating hematologic malignancies.

Results

Genetic editing of CD38 universal CAR-T cells, including CD38, T cell receptor alpha constant (TRAC), beta-2-microglobulin (B2M), and class II major histocompatibility complex transactivator (CIITA) knockdowns, was successfully achieved. In vitro, LLT1 overexpression boosted CAR-T cell proliferation and antitumor activity, leading to a transcriptional signature characterized by elevated stemness-related markers (SELL, BCL6, TCF7, and CD27) and increased levels of IL-10 and other cytokines. It also effectively mitigates rejection by allogeneic NK and T cells. In a humanized T-cell acute lymphoblastic leukemia (T-ALL) model, CD38 allogeneic universal CAR-T cells demonstrated superior survival rates and tumor clearance with reduced inflammatory responses.

Conclusion

According to these results, LLT1 overexpression enhances UCAR-T cell activity and prevents allogeneic rejection, providing essential insights for the development of universal CAR-T cell therapy.
Binding and cleavage of pro-urokinase by a tegument extract of Fasciola hepatica newly excysted juveniles activate the host fibrinolytic system
Authors: Serrat Judit , Torres-Valle María , De Marco Verissimo Carolina , Siles-Lucas Mar , González-Miguel Javier
Published: January 2025

Plasmin, the final product of fibrinolysis, is a broad-spectrum serine protease that degrades extracellular matrix (ECM) components, a function exploited by multiple pathogens for dissemination purposes. The trematode Fasciola hepatica is the leading cause of fasciolosis, a major disease of livestock and an emerging zoonosis in humans. Infection success depends on the ability of F. hepatica newly excysted juveniles (FhNEJ) to penetrate the host intestinal wall, a process that remains incompletely understood. We have previously shown that FhNEJ are capable of binding plasminogen (PLG), the zymogen of plasmin, on their tegument surface, which leads to plasmin generation in the presence of host-derived PLG activators and subsequent degradation of laminin, a major component of the intestinal ECM. Here, we describe the interaction between a tegument extract of FhNEJ and the precursor of the urokinase-type PLG activator (pro-u-PA). We found that F. hepatica cathepsins B3, L3, enolase and glutathione S-transferase mediate this interaction, suggesting a multifactorial or moonlighting role for these proteins. Additionally, our results revealed that the tegument of FhNEJ contains a protease that is capable of cleaving and activating pro-u-PA into its catalytically active form, which positively impacts the capacity of the parasites to generate plasmin from the host PLG. Collectively, our findings indicate that FhNEJ interact with the host fibrinolytic system at multiple levels, reinforcing the potential of targeting this interaction as a strategy to prevent FhNEJ trans-intestinal migration and infection success.
Impact of mechanical ventilation on severe acute kidney injury in critically ill patients with and without COVID-19 – a multicentre propensity matched analysis
Authors: Perschinka Fabian , Mayerhöfer Timo , Engelbrecht Teresa , Graf Alexandra , Zajic Paul , Metnitz Philipp , Joannidis Michael
Published: January 2025

Background

Acute kidney injury (AKI) is common in critically ill patients and is associated with increased morbidity and mortality. Its complications often require renal replacement therapy (RRT). Invasive mechanical ventilation (IMV) and infections are considered risk factors for the occurrence of AKI. The use of IMV and non-invasive ventilation (NIV) has changed over the course of the pandemic. Concomitant with this change in treatment a reduction in the incidences of AKI and RRT was observed. We aimed to investigate the impact of IMV on RRT initiation by comparing critically ill patients with and without COVID-19. Furthermore, we wanted to investigate the rates and timing of RRT as well as the outcome of patients, who were treated with RRT.

Results

A total of 8,678 patients were included, of which 555 (12.8%) in the COVID-19 and 554 (12.8%) in the control group were treated with RRT. In the first week of ICU stay the COVID-19 patients showed a significantly lower probability for RRT initiation (day 1: p < 0.0001, day 2: p = 0.021). However, after day 7 a reversed HR was found. In mechanically ventilated patients the risk was significantly higher for the initiation of RRT over the entire stay. While in non-COVID-19 patients this was a non-significant trend, in COVID-19 patients the risk for RRT was significantly increased. The median delay between initiation of IMV and requirement of RRT was observed to be longer in COVID-19 patients (5 days [IQR: 2–11] vs. 2 days [IQR: 1–5]). The analysis restricted to patients with RRT showed a significantly higher risk for ICU death in patients requiring IMV compared to patients without IMV.

Conclusion

The analysis demonstrated that IMV as well as COVID-19 are associated with an increased risk for initiation of RRT. The association between IMV and risk of RRT initiation was given for all investigated time intervals. Additionally, COVID-19 patients showed an increased risk for RRT initiation during the entire ICU stay within patients admitted to an ICU due to respiratory disease. In COVID-19 patients treated with RRT, the risk of death was significantly higher compared to non-COVID-19 patients.
Yeast cell wall polysaccharides accelerate yet in-feed antibiotic delays intestinal development and maturation via modulating gut microbiome in chickens
Authors: Guo Fangshen , Qiao Jianing , Hu Zeqiong , Huang Jia , Bi Ruichen , Abbas Waseem , Zhen Wenrui , Guo Yuming , Wang Zhong
Published: January 2025

Background

It is important to promote intestinal development and maturation of chicks for feed digestion and utilization, intestinal health, and disease resistance. This study aimed to investigate the effects of dietary yeast cell wall polysaccharides (YCWP) addition on intestinal development and maturation of chickens and its potential action mechanism.

Methods

180 one-day-old male Arbor Acres broilers were randomly assigned to three groups containing control (basal diets without any antibiotics or anticoccidial drug), bacitracin methylene disalicylate (BMD)-treated group (50 mg/kg) and YCWP-supplemented group (100 mg/kg).

Results

Compared with control group, in-feed antibiotic BMD continuous administration significantly decreased crypt depth (d 21) and villus height (d 42) along with mucosal maltase activity (d 42) in the ileum (P < 0.05). Also, BMD markedly downregulated gene expression levels of β-catenin, lysozyme, occludin and FABP-2 (d 21) and innate immune related genes CD83 and MHC-I mRNA levels (d 42, P < 0.05), and decreased goblet cell counts in the ileum of chickens (d 21 and d 42, P < 0.05). While, TLR-2, TLR-6 and iNOS mRNA abundances were notably upregulated by BMD treatment (d 42, P < 0.05). Nevertheless, dietary YCWP addition significantly increased the ratio of villus height to crypt depth (d 21), villus surface area (d 21 and d 42), ileal alkaline phosphatase and maltase activities as well as goblet cell (d 21 and d 42) and IgA-producing plasma cell numbers as compared to BMD treatment (d 21, P < 0.05). YCWP addition also upregulated gene expression levels of Lgr5, Wnt/β-catenin signaling pathway related gene (Wnt3, β-catenin, d 21; β-catenin, d 42), intestinal cells proliferation marker Ki-67 and barrier function related genes (occludin, d 21 and d 42, P < 0.05). Moreover, YCWP significantly increased antigen presenting cell marker related genes (MHC-II, d 21; CD83 and MHC-I, d 42), TLR-1, TLR-2 and TLR-6 mRNA levels (d 21, P < 0.05). Cecal microbiome analysis showed that YCWP addition obviously improved cecal microbial composition, as indicated by increasing relative abundance of Fournierella, Psychrobacter and Ruminiclostridium on d 21, and Alistipes and Lactobacillus on d 42, which were positively related with gut development and maturation related indexes (P < 0.05).

Conclusion

Collectively, YCWP promoted yet antibiotic BMD delayed intestinal morphological and immunological development linked with modulating gut microbiome in chickens.