bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the impact of working conditions on ranger vulnerability to corruption: insights from a global survey
Authors: Lebon Héloïse , Singh Rohit , Abdulla Amal Fathima , Ahmed Kaleem , Aisha Hamera
Published: November 2024

Rangers play a crucial role on the frontline of conservation; however, they often face difficult and sometimes dangerous working conditions, along with inadequate pay, equipment, training, and recognition. This study aims to determine the influence of rangers’ working conditions on their vulnerability to corruption using correlation analysis. The research utilized the Global Ranger Perception Survey 2019 dataset, a global-scale survey that collected responses from 6,101 rangers across 25 countries on various aspects of their working conditions. We further analyzed the results by gender and geographic region. Key findings indicate that women have a lower propensity to engage in corrupt activities. Conversely, at the regional level, Latin America demonstrates a heightened susceptibility to corruption compared to other regions. Additionally, there is a strong correlation between corruption and certain aspects of rangers’ working conditions in Latin America. Future assessments, such as the State of the Ranger Report, could provide a monitoring mechanism to evaluate the long-term effects of improvements in rangers' working conditions and their potential vulnerability to corruption worldwide. Country-specific or even landscape-specific in-depth studies would be valuable for developing targeted strategies to address corruption within the workforce while also improving rangers’ working conditions.
Charge-coupled device readout by digital-correlated double sampling
Authors: Cruz Carlos , De Vicente Juan
Published: November 2024

Charge-coupled devices (CCDs) play crucial roles in astronomy owing to their widespread use in the optical band, offering high sensibility, low noise, high dynamic range, and high spatial resolution. Recent advancements in CCDs have focused on improving the sub-electron noise levels for particle detection and enhancing readout speeds through simulation studies. The main objective of this study is to replace the analog processing of CCD signals using the digital-correlated double sampling (DCDS) technique. DCDS allows post-acquisition noise correction through intermittent sampling of an internal reference voltage to provide compact and flexible performance. In this study, DCDS was evaluated using two digital processing systems, namely, a 2.5 mega-samples per second (MSPS) 24-bit analog-to-digital converter (ADC) board and a 250 MSPS 16-bit ADC field-programmable-gate-array( FPGA)-based buffer memory board. The readout noise value at 74 kpix/s (7.1 e) was a significant improvement over that obtained with analog processing (9.7 e). The DCDS implementation demonstrates optimal signal-to-noise ratio for a wide range of readout speeds. Parameters such as the sample positions per pixel, number of samples, and number of pixels were identified to be essential in achieving an accurate gain value. Finally, hardware implementation of the DCDS IP core algorithm on a Xilinx Zynq-7000 AP system-on-a-chip (SoC) showed a significant improvement in power dissipation (7.1 W) compared to the analog Monsoon correlated double sample (CDS) circuit (13.6 W). The DCDS IP core implementation also showed a background noise reduction of up to 34% compared to DCDS offline readout processing using a Python algorithm.
Analysis of deformation evolution characteristics of the northern Lajishan fault before the Jishishan MS6.2 earthquake based on GNSS observations
Authors: Liao Jiayan , Ma Haiping , Feng Jiangang , Li Minjuan , Zhang Jinpeng
Published: November 2024

A MS6.2 earthquake struck Jishishan Country in Gansu Province on 18 December 2023. The earthquake occurred on the eastern branch of the Northern Lajishan fault (NLJSF) which has never experienced such a violent seismic event in recorded history. In this study, multiple periods of GNSS campaign observation data and continuous observation data are collected to reveal the crustal deformation evolution characteristics of the eastern branch of the NLJSF before the earthquake, focusing on the dynamic behavior of the causative fault, regional strain parameter features, and the variation of GNSS baselines across the NLJSF. Velocity field data show that the differential movement on both sides of the fault zone before the earthquake accumulated energy for the occurrence of the earthquake. Cross-fault profile analyses indicate a noticeable weakening of horizontal shortening on both fault flanks, suggesting a nearing fault lockup. The baseline time series and strain parameter time series results both show that the study area is mainly NEE-trending compression deformation. In addition, before the earthquake, multiple baseline results and strain parameter time series deviated from the linear trend and gradually flattened, indicating a strain accumulation in the study area. The overall crustal deformation evolution shows a relatively high earthquake risk before the Lajishan earthquake.
Optimization method for predicting coal reservoir fractures in the Laochang area of Eastern Yunnan using paleotectonic stress inversion
Authors: Wu Changwu , Wang Bo , Hu Xiong , Jin Xue , Liang Wei , Shi Mingjian , Zhu Xueguang , Guo Liang
Published: November 2024

Introduction

Coal reservoir fractures serve as critical storage spaces and migration pathways for coalbed methane (CBM), significantly influencing CBM enrichment. The characteristics of coal reservoir fracture development can be obtained using traditional simulation methods, but these still have shortcomings. This work presents an optimization approach for the traditional method.

Methods

This study introduces an optimization approach for traditional methods with two novel contributions. This study integrates the simulation of tectonic stress fields with fracture prediction, using surface sandstone fractures as constraints to reconstruct the paleostress field of the coal seam, while also accounting for the influence of coal thickness on fracture development to calculate fracture density.

Results

The predicted fracture density results were validated against measured values from the Bailongshan mine and Xiongdong coal mine with a relative error of approximately 12%, suggesting a reasonable degree of reliability.

Discussion

Based on the results of the fracture simulation predictions, it is believed that the coal seam fracture density in the study area is mostly 10–20 lines/m and that the sweet spot for CBM development is located in the Yuwang block.
Assessment of group formation methods on performance in group-based learning activities
Authors: Bergtold Jason S. , Shanoyan Aleksan
Published: November 2024

Research on teaching and learning has demonstrated many benefits from team-and group-based learning for improving content comprehension and meeting learning outcomes in a wide range of disciplines. We help to expand on this research, by shedding additional light on the impact of group formation decisions on group performance during group learning activities in a higher education classroom setting. Our objective is to assess the impact of different group formation strategies, including random assignment, self-selection, and methods based on individual metrics, such as academic performance and individual skill levels. Using an experimental design approach, we find that GPA-based and math-ability based group formation strategies may provide some additional benefit to group performance on the margin when initially forming groups. Self-selection of groups may be more beneficial after students learn more about each other (e.g., skills sets and work ethic) during the progression of the course. Our study contributes to the literature by providing an assessment of different group formation strategies that are accessible to a wide range of instructors for small to large classes, as well as guidance on use of different group formation strategies within classes, specifically for classes with more quantitative and analytical tasks.
The use of autonomy among physical education teachers in Finland and Kurdistan region of Iraq
Authors: Lagestad Pål , Makrooni Golaleh , Mohammed Warhel Asim , Kalari Joonas
Published: November 2024

Introduction

The aim of the study was to examine fifth-grade physical education (PE) teachers’ reflections and perceptions about PE teaching in Finland and Kurdistan region of Iraq (KRI), using analyses of in-depth interviews with a phenomenological-hermeneutic approach.

Methods

This was accomplished by exploring eight Finnish and six KRI PE teachers’ opinions, attitudes, experiences, and reflections regarding their work as PE teachers, using semi-structured in-depth interviews about PE, as well as their reflections related to an indoor and an outdoor video from ordinary PE teaching in the other country. The initial analyses of the two groups of teachers using the qualitative analysis program NVivo revealed interesting findings related to student autonomy, and these differences were examined closely.

Results

While the analyses showed that all the Finnish PE teachers highlighted the importance of providing student autonomy within the open-ended questions related to PE, PE teachers in KRI seldom discussed autonomy during the open-ended questions. Instead, they seemed to organize their teaching in a way that decreased autonomy. The Finnish PE teachers indicated that the use of autonomy was central in the curriculum, and that they used autonomy to increase the students’ motivation and to make PE more meaningful for the students. With such a strategy, the use of autonomy would also activate and include more students, even if Finnish PE teachers reported certain challenges with students’ autonomy. The PE teachers from KRI, however, related PE to be mainly focused on performing sport activities and reflected a strategy of “just do as I do” - a strategy that created little room for autonomy, even if the findings pointed to some traces of autonomy among the PE teachers in KRI.

Discussion

Considering the findings and the theoretical concept of self-determination theory that highlight students’ autonomy as essential for students’ motivation, integration, wellness, and well-being in PE, our findings suggest that new perspectives and practices are needed among teachers in KRI to ensure autonomy in PE teaching. In this vein, increased exchange of experiences and collaboration between educators from Finland and KRI could be beneficial.
School contextualization with indigenous group’s socio-educational methods and pedagogies
Authors: Quilaqueo Daniel , Torres Héctor
Published: November 2024

This article presents a method for contextualizing school education and initial teacher training, using the case of Mapuche in schools in central-southern Chile to change the ambivalence of teaching in an indigenous context. The analysis is based on a dispositionalist-contextualist theoretical framework and the results of empirical research projects on Mapuche socio-educational knowledge. It examines the co-construction of intercultural knowledge by researchers and parents. It concludes with a Mapuche educational knowledge base that can contextualize the school curriculum and teacher training plans.
Lost in translation: error analysis of texts translated from Arabic into English by Saudi translators
Authors: Alluhaybi Maram
Published: November 2024

Biographic translation is crucial in today’s globalized world to preserve histories or shed light on the lives of people who influenced their nations or the world. The literature on biographic translation and the factors hindering such translation in an English as a foreign language (EFL) setting, especially in the Saudi context, is relatively limited. In the present study, the author analyzed the errors made by Saudi EFL learners when they translated a biography from Arabic into English. The data were drawn from a short text translated by female final-year university students as part of their course evaluations. The author conducted a qualitative analysis and classified errors according to Pospescu’s taxonomy. The results showed that the students committed all the three error types: linguistic, comprehensive, and translation. Within these three types, the students made diverse errors, ranging from misusing tenses to misspelling words. Consequently, their overall translations were unsatisfactory. This finding is helpful for both learners and educators, as the identified translation errors can be used as teaching aids in translation classes. The findings put emphasis on the importance of practice and prompt feedback as essential aids educators can use to support their students during their translation learning.
Influence of a chatbot based on a conversational agent on the adaptability of first-year students of a Peruvian private university
Authors: Mejia Yahaira Zileri Odalis Arapa , Navarro Christopher Andrew Dobson , Casildo-Bedón Nancy Esther , Pezo Yngue Elizabeth Ramirez
Published: November 2024

Objective

This study aims to evaluate the influence of using a chatbot-based conversational agent, named ODAbot, on the adaptability of first-year students at a private university in Peru.

Methods

The design of this study was pre-experimental with a quantitative approach. The sample consisted of 53 university students who participated in the research during March and April 2024. Participants completed pre-test and post-test questionnaires to assess their adaptability to university life before and after interacting with ODAbot. Additionally, a user experience questionnaire was used to measure satisfaction with the chatbot interaction. Data were analyzed using the Wilcoxon test to determine the statistical significance of the results.

Results

The results showed that the use of ODAbot had a significant impact on students’ adaptability, especially in the social dimension (p = 0.000), while no significant differences were found in the institutional dimension (p = 0.124). The user experience was positive, with students reporting ease of navigation and understanding of the responses provided by the chatbot.

Conclusion

A notable improvement was recorded in the social dimension, promoting peer integration, as well as in the academic dimension, where students expressed greater satisfaction with the information provided. However, no significant differences were observed in the institutional dimension. Overall, the implementation of chatbots presents a promising opportunity to improve the adaptability of university students and ensure a quality educational experience.
Building a valuable professional development course: instructor effort vs. perceived student value of activities in an online biotechnology course
Authors: Chen Stefanie H. , Dums Jacob T. , Hasley Andrew O.
Published: November 2024

Providing undergraduate and graduate students with the appropriate preparation for transitioning to careers in their field after graduation is a key goal of higher education institutions, with many programs employing professional development workshops or courses to assist students and provide hands-on skills in this area. Although a wide variety of activities could benefit students, instructor and career specialist time is limited. Here, we describe an online biotechnology professional development course for undergraduate and graduate students, covering career exploration and the job search process, and the students’ perceptions of the activities offered based on survey data. Overall response to the course was positive, with students at various stages of their education indicating appreciation of most of the course assignments. Interestingly, students ranked the activities that took the most instructor time, namely review of application materials, mock interviews, and career panels, as the most valuable for their personal development. The career exploration aspects of the course influenced students to be open to new possibilities. However, students struggled to make time to complete the assignments for a fully online, largely asynchronous course. Discussion of the value of the course activities, their relevance to social cognitive career theory and cognitive information processing, and suggestions for smooth implementation are provided.
The effect of foreign language enjoyment on willingness to communicate among Chinese EFL students: conscientiousness as a mediator
Authors: Zhao Jin , Guan Kaining , Feng Yu , Liu Ziqing
Published: November 2024

Introduction

An increasing body of research has explored the predictive effect of personality traits and affective factors on EFL learners’ willingness to communicate (WTC). However, more is needed to know about how the sub-facets of individual personality traits influence WTC in the classroom context. Therefore, drawing on positive psychology, this study aims to bridge this gap by examining these roles in a mediation model of WTC incorporating FLE and conscientiousness.

Methods

To this end, 244 Chinese EFL undergraduates from two distinct universities participated in an online survey, completing a composite questionnaire of the three constructs. The bootstrapping technique was employed to test the proposed relationships.

Results

The findings indicated a positive correlation between both FLE and conscientiousness with WTC. Additionally, conscientiousness significantly mediated the relationship between FLE and WTC, supporting a partial mediation effect. Also, FLE had a direct influence on conscientiousness. These results may have some notable implications for EFL educators.

Discussion

The adoption of a holistic approach that emphasizes affective factors alongside acknowledging individual differences among learners could enhance students’ willingness to communicate in English.
Early scientific research training links to the innovation ability of medical undergraduates and postgraduates
Authors: Wang Boyang , Yang Lulu , Gong Zhaohui
Published: November 2024

Scientific research training (SRT) is crucial for fostering skills and innovation in college students. However, the status of SRT in medical undergraduates and postgraduates, as well as the impact of early SRT on students’ innovation abilities, remain largely unknown. This study assessed the role of SRT in culturing innovation abilities among medical students. The results revealed that undergraduates exhibited a greater understanding of scientific research compared to postgraduates. Notably, undergraduates demonstrated a higher level of understanding of SRT in contrast to postgraduates (81.26% vs. 56.97%). A significant proportion (>70%) of undergraduates had engaged in research activities early in their academic journey, with an average participation duration exceeding 1 year. Moreover, undergraduates initiated their involvement in SRT during the first- and second- year of undergraduates, which was earlier than postgraduates. Personal interest emerged as a primary motivator for engaging in SRT, with postgraduates exhibiting higher research aspirations and achieving greater research outcomes. Postgraduates also received more substantial guidance from advisors, leading to enhanced academic performance compared to undergraduates (90.7% vs. 67.59%). Interestingly, students expressed satisfaction with laboratory conditions and attributed their academic success to personal efforts. These findings underscore the importance of early SRT in cultivating the innovation abilities of medical students.
Glucagon-like peptide-1 receptor agonists and the risk of erectile dysfunction: a drug target Mendelian randomization study
Authors: An Hongjin , Xie Kexin , Gan Huatian
Published: November 2024

Background

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been widely used for type 2 diabetes (T2D) and weight management. However, the causal relationship of GLP-1RAs with erectile dysfunction (ED) was still unclear.

Methods

Mendelian randomization (MR) analysis was conducted to reveal the association of genetically proxied GLP-1RAs with ED. The proportion of potential mediators mediating GLP-1RAs to ED was also assessed by two-step MR. Finally, a series of sensitivity analyses and Two-Sep cis-MR (TSCMR) were performed to evaluate the robustness of the results.

Results

MR evidence suggested that genetically proxied GLP-1RAs reduced the risk of ED [odds ratio (OR): 0.493; 95% confidence interval (95% CI): 0.430 to 0.565; P<0.001]. Further mediation analysis via two-step MR showed that this effect was partly mediated through reduced T2D, obesity, hypertension and cardiovascular disease (CVD), with mediated proportions of 2.89% (95% CI: 1.28% to 4.49%), 6.83% (95% CI: 2.25% to 11.41%), 3.22% (95% CI: 1.21% to 5.23%), and 3.06% (95% CI: 0.51% to 5.62%), respectively.

Conclusions

GLP-1RAs were associated with a reduced risk of ED, and to a lesser extent, T2D, obesity, hypertension and CVD mediated this effect. Nevertheless, the potential implications of our results for ED prevention policies required validation in further clinical randomized controlled trials.
Research on the impact of the digital economy on haze pollution: evidence from prefecture-level cities in China
Authors: Liu Mingguang , Lin Churou , Zhou Yumin , Han Yuke , Feng Yue , Li Gaoyang
Published: November 2024

Lately, the ongoing issue of haze pollution in multiple cities across China has had a profound impact on the residents’ wellbeing and overall health. The urgent necessity to address haze pollution is undeniable. Meanwhile, the rapidly evolving digital economy has sprung up as a pivotal driver for China’s economic growth, providing innovative approach to tackle haze pollution. This research explores the impact of the digital economy on haze pollution through utilizing the big data pilot zone as a quasi-natural experiment. Panel data from 280 prefecture-level cities in China is adopted, covering the period from 2011 through 2020. This analysis incorporates various models, namely, difference-in-differences model (DID), mediation effect model, and difference-in-differences spatial Durbin model. The findings highlight the substantial contributions of digital economy in alleviating haze pollution. Furthermore, these findings hold true even after a series of rigorous robustness checks. The constraint influence of the digital economy on haze pollution is particularly prominent in metropolitan areas, cities with elevated administrative levels, primary environmental protection cities, as well as economically developed cities. Financial development and technological innovation serve as important mechanisms through which the digital economy suppresses haze pollution. After accounting for spatial factors, the digital economy exhibits consequential spillover effects, leading to substantial inhibition of haze pollution in surrounding cities as well as locally. The novel aspects of this paper are as follows: Firstly, it regards the establishment of big data experimental zones as the exogenous policy shock of digital economy and employs a multi period DID model to evaluate the impact of the digital economy on haze pollution. Secondly, it explores the transmission pathways through which the digital economy affects haze pollution from the perspectives of financial development and technological innovation. Thirdly, it investigates the heterogeneous characteristics of the impact of the digital economy on haze pollution. Fourthly, it examines the spatial spillover effects of the digital economy on haze pollution from the perspective of spatial econometrics.
Do green investments impact corporate green innovation?empirical evidence from Chinese-listed companies
Authors: Zhang Yiru , Shou Songtao , Li Youhuan
Published: November 2024

The rapid expansion of the global economy has exacerbated environmental concerns, thereby prompting a shift in resource allocation from polluting industries to green sectors. This transition is pivotal for sustainable development, with capital playing a central role in mobilizing resources to foster green innovation. This study examines data from Chinese-listed companies between 2012 and 2022 to evaluate the impact of green investment on corporate green innovation. The analysis incorporates a comprehensive review of financial records and innovation metrics to establish a correlation between investment and innovation outcomes. The findings reveal a positive correlation between increased green investment and enhanced green innovation, with a more pronounced effect observed in private enterprises and industries characterized by high competition. Green investment primarily stimulates innovation by alleviating financial constraints. These results emphasize the crucial role of green investment in promoting sustainable corporate practices. Furthermore, they provide valuable insights for policymakers in formulating effective green investment strategies, which are essential for China’s transition toward a green economy.
Heatwave-amplified atmospheric oxidation in a multi-province border area in Xuzhou, China
Authors: Zhang Guoxian , Yu Xingyu , Yin Hao , Feng Chunli , Ma Chao , Sun Shiqiang , Cheng Haoqiang , Wang Shiyu , Shang Kunqi , Liu Xiaoyan
Published: November 2024

Ozone formation is closely tied to emissions of precursors, meteorological conditions, and atmospheric chemistry. In June 2024, Xuzhou City, located at the intersection of Jiangsu, Shandong, Henan, and Anhui provinces in East China, experienced a series of ozone pollution events. The continuous pollution episodes were characterized by consistently high levels of ozone, with daytime peaks reaching 130 ppb. By combining observations of atmospheric oxidation and the use of the Observation-Based Model model, it was determined that the pollution was the result of a “heatwave-ozone” co-occurring extreme event triggered by elevated temperatures, low humidity, and intense radiation. The heatwave led to increased emissions of VOCs from both natural and human-related sources, with more pronounced contribution from Bio-alkenes and OVOCs. This, in turn, resulted in higher levels of oxidizing agents and ozone formation potential, exacerbating the co-occurrence of heatwaves and ozone extremes. Sensitivity tests on enhanced controls showed that reducing NOx had a significant adverse effect on ozone levels, whereas reducing VOCs had positive benefits, particularly for controlling alkenes. Despite ongoing reductions in anthropogenic VOCs, the elevated temperatures led to an increase in natural VOCs emissions. On average, a 1°C temperature decrease could reduce the reactivity ratio of VOCs to NOx (VOCR/NOxR) by 0.12, thereby enhancing the advantages of emission reductions. Therefore, implementing measures to alleviate extreme heatwaves, such as limiting high-energy consumption and inducing artificial rainfall, can simultaneously reduce the intensity and reactivity of VOC emissions, aiding in the effective implementation of ozone pollution control policies.
Integrative analysis of single-cell transcriptomic and multilayer signaling networks in glioma reveal tumor progression stage
Authors: Atanaki Fereshteh Fallah , Mirsadeghi Leila , Manesh Mohsen Riahi , Kavousi Kaveh
Published: November 2024

Introduction

Tumor microenvironments (TMEs) encompass complex ecosystems of cancer cells, infiltrating immune cells, and diverse cell types. Intercellular and intracellular signals within the TME significantly influence cancer progression and therapeutic outcomes. Although computational tools are available to study TME interactions, explicitly modeling tumor progression across different cancer types remains a challenge.

Methods

This study introduces a comprehensive framework utilizing single-cell RNA sequencing (scRNA-seq) data within a multilayer network model, designed to investigate molecular changes across glioma progression stages. The heterogeneous, multilayered network model replicates the hierarchical structure of biological systems, from genetic building blocks to cellular functions and phenotypic manifestations.

Results

Applying this framework to glioma scRNA-seq data allowed complex network analysis of different cancer stages, revealing significant ligand‒receptor interactions and key ligand‒receptor-transcription factor (TF) axes, along with their associated biological pathways. Differential network analysis between grade III and grade IV glioma highlighted the most critical nodes and edges involved in interaction rewiring. Pathway enrichment analysis identified four essential genes—PDGFA (ligand), PDGFRA (receptor), CREB1 (TF), and PLAT (target gene)—involved in the Receptor Tyrosine Kinases (RTK) signaling pathway, which plays a pivotal role in glioma progression from grade III to grade IV.

Discussion

These genes emerged as significant features for machine learning in predicting glioma progression stages, achieving 87% accuracy and 93% AUC in a 3-year survival prediction through Kaplan-Meier analysis. This framework provides deeper insights into the cellular machinery of glioma, revealing key molecular relationships that may inform prognosis and therapeutic strategies.
Human CFTR deficient iPSC-macrophages reveal impaired functional and transcriptomic response upon Pseudomonas aeruginosa infection
Authors: Rodriguez Gonzalez Claudio , Basílio-Queirós Débora , Neehus Anna-Lena , Merkert Sylvia , Tschritter David , Ünal Sinem , Hegermann Jan , Mörgelin Matthias , Bustamante Jacinta , Nietert Manuel Manfred , Martin Ulrich , Tümmler Burkhard , Munder Antje , Lachmann Nico
Published: November 2024

Introduction

Cystic fibrosis (CF) is a hereditary autosomal recessive disease driven by deleterious variants of the CFTR gene, leading, among other symptoms, to increased lung infection susceptibility. Mucus accumulation in the CF lung is, as of yet, considered as one important factor contributing to its colonization by opportunistic pathogens such as Pseudomonas aeruginosa. However, in recent years evidence was provided that alveolar macrophages, which form the first line of defense against airborne pathogens, seem to be intrinsically defective with regard to bactericidal functionality in the CF lung. To assess the impact of CFTR deficiency in human macrophages only insufficient systems are available.

Methods

To address this problem and to evaluate the role of CFTR in human macrophages, we successfully differentiated human induced pluripotent stem cells (iPSC) from a CF p.Phe508del homozygous individual and a healthy donor into primitive macrophages (iMacΔF508 and iMacWT), respectively, and compared the bactericidal functionality in the relevant cell type.

Results

iMacΔF508 showed impaired P. aeruginosa clearance and intracellular killing capacity in comparison to iMacWT. Furthermore, iMacΔF508 exhibited a less acidic lysosomal pH, and upon P. aeruginosa infection, there were signs of mitochondrial fragmentation and autophagosome formation together with a hyperinflammatory phenotype and deficient type I interferon response.

Conclusion

In summary, we present a defective phenotype in iMacΔF508 upon P. aeruginosa infection, which will constitute an ideal platform to further study the role of macrophages in the context of CF.
Longitudinal mitochondrial bioenergetic signatures of blood monocytes and lymphocytes improve during treatment of drug-susceptible pulmonary tuberculosis patients
Authors: Cumming Bridgette M. , Addicott Kelvin W. , Maruri Fernanda , Pillay Vanessa , Asmal Rukaya , Moodley Sashen , Barreto-Durate Beatriz , Araújo-Pereira Mariana , Mazibuko Matilda , Mhlane Zoey , Mbatha Nikiwe , Khan Khadija , Makhari Senamile , Karim Farina , Peetluk Lauren , Pym Alexander S. , Moosa Mahomed Yunus S. , van der Heijden Yuri F. , Sterling Timothy S. , Andrade Bruno B. , Leslie Alasdair , Steyn Adrie J. C.
Published: November 2024

The impact of human pulmonary tuberculosis (TB) on the bioenergetic metabolism of circulating immune cells remains elusive, as does the resolution of these effects with TB treatment. In this study, the rates of oxidative phosphorylation (OXPHOS) and glycolysis in circulating lymphocytes and monocytes of patients with drug-susceptible TB at diagnosis, 2 months, and 6 months during treatment, and 12 months after diagnosis were investigated using extracellular flux analysis. At diagnosis, the bioenergetic parameters of both blood lymphocytes and monocytes of TB patients were severely impaired in comparison to non-TB and non-HIV-infected controls. However, most bioenergetic parameters were not affected by HIV status or glycemic index. Treatment of TB patients restored the % spare respiratory capacity (%SRC) of the circulating lymphocytes to that observed in non-TB and non-HIV infected controls by 12 months. Treatment also improved the maximal respiration of circulating lymphocytes and the %SRC of circulating monocytes of the TB patients. Notably, the differential correlation of the clinical and bioenergetic parameters of the monocytes and lymphocytes from the controls and TB patients at baseline and month 12 was consistent with improved metabolic health and resolution of inflammation following successful TB treatment. Network analysis of the bioenergetic parameters of circulating immune cells with serum cytokine levels indicated a highly coordinated immune response at month 6. These findings underscore the importance of metabolic health in combating TB, supporting the need for further investigation of the bioenergetic immunometabolism associated with TB infection for novel therapeutic approaches aimed at bolstering cellular energetics to enhance immune responses and expedite recovery in TB patients.
The role of neutrophils in tPA thrombolysis after stroke: a malicious troublemaker
Authors: Li Qingcan , Ye Jiao , Li Zhifang , Xiao Qinghui , Tan Senwei , Hu Bo , Jin Huijuan
Published: November 2024

Acute ischemic stroke represents a critical, life-threatening condition affecting the central nervous system. Intravenous thrombolysis with tissue plasminogen activator (tPA) remains a cornerstone for achieving vascular recanalization in such patients; however, its therapeutic utility is limited, with only approximately 10% of patients benefiting due to the narrow therapeutic window and significant risk of hemorrhagic transformation. Enhancing the efficacy of tPA thrombolysis is therefore imperative. Neutrophils have been identified as key modulators of thrombolytic outcomes, interacting with tPA post-stroke to influence treatment effectiveness. The binding of tPA to low-density lipoprotein receptor-related protein 1 (LRP-1) on neutrophil surfaces induces degranulation and formation of neutrophil extracellular traps (NETs). Conversely, neutrophils impede the thrombolytic action of tPA by obstructing its interaction with fibrin and activating platelets. These findings suggest that targeting neutrophils may hold promise for improving thrombolysis outcomes. This review explores the role of neutrophils in tPA-mediated thrombolysis following acute ischemic stroke, examines neutrophil-associated biomarkers, and outlines potential strategies for enhancing tPA efficacy.
Advances in research on the relationship between mitochondrial function and colorectal cancer: a bibliometric study from 2013 to 2023
Authors: Liu Jinhui , Chang Yonglong , Ou Qinling , Chen Linzi , Yan Haixia , Guo Duanyang , Wang Chongjie , Zhang Sifang
Published: November 2024

The study provides a thorough examination of literature from 2013 to 2023, delving into the intricate relationship between mitochondrial function and colorectal cancer (CRC). It offers a concise overview of the current landscape and emerging trends in this rapidly evolving research area. The findings indicate a consistent rise in annual publications, reflecting growing interest and significant potential in the field. China emerges as the leading contributor, followed by the United States and India. However, despite China’s dominance in output, its average citation rate is lower than that of the US, which leads in citations per publication, highlighting a noticeable disparity. In the realm of research institutions, Shanghai Jiao Tong University and China Medical University are identified as major contributors, yet the potential for inter-institutional collaboration remains largely untapped, suggesting avenues for future synergy. Internationally, China-US collaborations are particularly robust, fostering cross-border knowledge exchange. Hyun Jin Won and Li Wei are recognized as prolific authors, while Ahmedin Jemal is an influential co-cited scholar, noted for his seminal contributions. Keyword analysis reveals research focus areas, such as the complex CRC tumor microenvironment, molecular mechanisms of oxidative stress, and key multidrug resistance pathways. It also highlights the promising potential of mitochondria-targeted therapies and nanomolecular technologies in clinical practice, signaling their growing significance in addressing complex health challenges. The study underscores the imperative to validate complex mitochondrial mechanisms and signaling pathways in CRC, with a particular emphasis on translating these insights into drug targets for clinical trials. Advancing this research is expected to refine and enhance CRC treatment strategies. Additionally, it highlights the urgency of validating mitochondrial complexities in CRC, advocating for collaborative efforts to link these mechanisms with tailored therapeutic interventions for clinical testing. This integrated approach promises significant advancements in developing effective, targeted CRC treatments, ultimately improving patient outcomes.
IGF2BP1 accelerates the aerobic glycolysis to boost its immune escape in hepatocellular carcinoma microenvironment
Authors: Ye Xuxing , Lin Junmei , Chen Yanping , Wang Xiaobo
Published: November 2024

Introduction

Energy metabolism abnormity emerges as a crucial factor that facilitates tumorigenesis by accelerating aerobic glycolysis. However, the function of N6-methyladenosine (m6A) on hepatocellular carcinoma (HCC) aerobic glycolysis and immune escape is still unclear. Here, this investigation was intended to elucidate the regulation of m6A ‘reader’ IGF2BP1 involved in HCC aerobic glycolysis and immune escape.

Methods

The aerobic glycolysis was tested by glucose uptake, lactate, ATP generation and ECAR. The CD8+ T cell-mediated killing effect was tested by cytotoxicity, IFN-γ and granzyme B. The molecular interaction was confirmed by luciferase reporter assay, immunoprecipitation assay and chromatin immunoprecipitation (ChIP)-PCR.

Results

Elevated IGF2BP1 expression was associated with poor prognosis in HCC patients. Functionally, IGF2BP1 emerged as an oncogenic factor that accelerated HCC aerobic glycolysis (glucose uptake, lactate, ATP generation and ECAR) and oxaliplatin resistance. Meanwhile, IGF2BP1 repressed the activated CD8+ T cell-mediated killing effect (cytotoxicity, IFN-γ and granzyme B) and apoptosis of HCC cells, indicating a suppressed cytotoxic T-cell response. By recognizing and binding to the m6A-modified sites on c-Myc mRNA, IGF2BP1 enhanced the stability of c-Myc mRNA, consequently upregulating c-Myc expression. In addition, transcription factor c-Myc targeted the programmed death ligand 1 (PD-L1) promoter region to strengthen its transcription.

Discussion

Taken together, this study illustrates IGF2BP1 as a potential therapeutic target in HCC, aiming to disrupt the interplay between aberrant metabolism and immune escape.
Protective effects of YCHD on the autoimmune hepatitis mice model induced by Ad-CYP2D6 through modulating the Th1/Treg ratio and intestinal flora
Authors: Wu Jiawen , Lyu Sixue , Guo Di , Yang Na , Liu Yang
Published: November 2024

Background

Autoimmune hepatitis (AIH) is a chronic liver inflammatory disease mediated by autoimmune reactions, the pathogenesis of AIH is probably related to the imbalance of intestinal flora. Yinchenhao decoction (YCHD) has been used to relieve AIH. However, the mechanisms underpinning YCHD’s hepatoprotective effects with the gut microbito have not been fully revealed.

Objective

To explore the potential mechanism of YCHD in treating AIH based on changes in the intestinal flora and Th1/Treg ratio in the spleen and hepatic hilar lymph nodes.

Methods

The AIH mice model induced by the adenovirus vectors that overexpress human cytochrome P450 family 2 subfamily D member 6 (Ad-CYP2D6) was established (untreated group). One week after the Ad-CYP2D6 injection, the AIH model mice were treated by administering YCHD by gavage for 14 days (YCHD-treated group). The therapeutic efficacy of YCHD on AIH was evaluated by detecting the histopathological changes of the liver, serum transaminases (ALT and AST), inflammatory factors (TNF-α,IL-17 and IFN-γ), and autoantibodies (including LKM-1 and LC-1). The ratio of Th1 to Treg within the spleen and hepatic hilar lymph nodes of the mice was detected by flow cytometry. The changes in the species and abundance of intestinal flora and intestinal flora metabolites were analyzed via 16S rRNA gene sequencing and gas chromatography-mass spectrometry (GC/MS) to reveal the protective mechanism of YCHD on liver injury.

Result

YCHD decreased the transaminase activity (AST and ALT), the content of autoantibodies (LC-1 and LKM-1), and the serum TNF-α, IL-12, and IL-17 levels in AIH mice. The degree of inflammatory infiltration in the YCHD-treated group was significantly less than that in the untreated group. YCHD can effectively reverse the abundance and diversity of intestinal flora in AIH mice and affect the release of short-chain fatty acids (SCFAs), especially butyric acid. Moreover, the flow cytometry results showed that YCHD could also decline the ratio of Th1/Treg, which probably be induced by SCFAs via the G protein-coupled receptor (GPR).

Conclusion

YCHD may affect the release of SCFAs by regulating the intestinal microbiota, thereby affecting the differentiation of Th1 and Treg, and achieving the effect of alleviating liver damage.
Extraordinary diversity of the CD28/CTLA4 family across jawed vertebrates
Authors: Quiniou Sylvie M. A. , Clark Thomas , Bengtén Eva , Rast Jonathan P. , Ohta Yuko , Flajnik Martin , Boudinot Pierre
Published: November 2024

Members of the CD28 family are critical for the control of immune cell activation. While CD28 and CTLA4 were previously identified in teleost fish, most members of the CD28 family have been described only in tetrapods. Using a comparative genomics approach, we found (co)orthologs of all members of the CD28 family both in Chondrichthyes and basal Osteichthyes groups, but not in Agnathans. Four additional members of the family were identified, which were present in both Chondrichthyes and Osteichthyes, some even in the tetrapod lineage but all of them absent in human. Herein, we extend the composition of the jawed vertebrate CD28 family to nine members: CD28, CTLA4, ICOS, CD28H, CD28HL1, CD28HL2, CD28HL3, CD28X and PD-1. Each of these genes had a single extracellular IgSF V domain, and conserved motifs in the V and the cytoplasmic domain. While a genomic cluster of three consecutive genes like CD28/CTLA4/ICOS was conserved across jawed vertebrates except in teleosts, the other members of the CD28 family were located on multiple chromosomes. Our findings show that these co-stimulatory/co-inhibitory receptors likely arose in early jawed vertebrates, and diversified when the Ig/TCR/MHC-based adaptive immunity emerged, heralding the advent of complex regulatory networks controlling lymphocyte activation.
Addressing barriers to post-graduate research training in low resource settings: an innovative approach in an institution of higher learning in Kenya
Authors: Mwangi Eunice Muthoni , Iseme-Ondiek Rosebella Alungata , Riang'a Roselyter Monchari , Orwa James , Njenga Kennedy W. , Ngugi Anthony K.
Published: November 2024

Background

Numerous barriers hinder health research training in Post-Graduate Medical Education Programs, especially in developing countries. Research training is pivotal for medical residency, providing essential knowledge and skills for dissertation completion, fostering evidence-based medical practice, and nurturing future independent clinical researchers. A holistic approach to research education is imperative to surmount these barriers. We describe here a dissertation-centric research curriculum, delivered longitudinally, an innovative strategy undertaken by Aga Khan University's Medical College in East Africa (AKU-MCEA) to deliver postgraduate research.

Methods

A review of AKU-MCEA post-graduate research methods curriculum was conducted based on implementing Departments' experience, institutional policies, and residency program output.

Program implementation

The Master of Medicine program requires a well-executed dissertation for graduation. Residents undergo structured research training across four modules, with interactive sessions and workshops supporting their research milestones. Protected time allows residents to develop and report on their dissertation work. Faculty receive specialized training in dissertation supervision to ensure residents benefit from expert guidance in producing high-quality research.

Outcomes

This approach achieves a dissertation completion and graduation rate of 98–100%. Notably, 68.5% (n = 126) of those who graduated in 2013–2023 have published two or more papers (i.e., range 2–36) in their current portfolio, demonstrating a commitment to ongoing research endeavors even after graduation. Residents' research covers diverse themes and is disseminated through departmental presentations, university-wide Faculty Academic Rounds, peer-reviewed journals, conferences, and the Annual Early Career Researchers symposium.

Lessons learnt

A comprehensive approach featuring a structured research curriculum, longitudinal delivery with predetermined milestones, dedicated supervision, financial and resource support, protected research time, ongoing faculty development in dissertation supervision, and clear institutional research policies accelerates dissertation completion and enhances effective research dissemination.
Mechanism of medical hemorrhoid gel in relieving pruritus ani via inhibiting the activation of JAK2/STAT3 pathway
Authors: Ai Zhongzhu , Yuan Dongfeng , Cai Jingyi , Dong Ruotong , Liu Wei , Zhou Daonian
Published: November 2024

Background

Pruritus ani (PA), a neurofunctional dermatosis, is one of the most common complications of hemorrhoids, which seriously affects the quality of life of patients. Medical hemorrhoid gel (MHG), a product mainly composed of herbal medicine, is widely used for treatment of PA clinically. This study aim to assess the alleviating effect and mechanism of MHG on PA based on rectal epidermis-spinal cord-brain axis using animal models.

Methods

A chloroquine-induced mouse itching model and a croton oil preparation-induced rat hemorrhoid model were established to evaluate anti-PA effect of MHG. Scratching behaviors of mice were recorded, and histopathology of mice skin and rat ano-rectal tissues was observed through H&E staining. Network pharmacology and western blotting were employed to explore potential mechanism of MHG.

Results

The study indicated that MHG significantly alleviated chloroquine-induced skin itching and improved pathological injuries in mice skin and rat ano-rectal tissues. Network pharmacology suggested that MHG might regulate the JAK/STAT signaling pathway. Experimental findings showed that MHG significantly downregulated TRPV1 and TRPA1 in rectal tissue, c-Fos and GRPR in spinal cord tissue, and 5-HT1a protein in brain tissue, while upregulating TRPM8 protein in rectal tissue. Furthermore, MHG inhibited the activation of the JAK2/STAT3 signaling pathway in the rectal epidermis-spinal cord-brain axis.

Conclusion

MHG improves PA by inhibiting the transmission of itching signals in rectal epidermis-spinal cord-brain axis via the JAK2/STAT3 signaling pathway, providing experimental evidence for its clinical application.