bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulated cell death in chronic kidney disease: current evidence and future clinical perspectives
Authors: Giuliani Kurt T. K. , Adams Benjamin C. , Healy Helen G. , Kassianos Andrew J. 
Published: October 2024

Chronic kidney disease (CKD) is the progressive loss of kidney function/structure over a period of at least 3 months. It is characterised histologically by the triad of cell loss, inflammation and fibrosis. This literature review focuses on the forms of cell death that trigger downstream inflammation and fibrosis, collectively called regulated cell death (RCD) pathways. Discrete forms of RCD have emerged as central mediators of CKD pathology. In particular, pathways of regulated necrosis – including mitochondrial permeability transition pore (mPTP)-mediated necrosis, necroptosis, ferroptosis and pyroptosis – have been shown to mediate kidney pathology directly or through the release of danger signals that trigger a pro-inflammatory response, further amplifying tissue injury in a cellular process called necroinflammation. Despite accumulating evidence in pre-clinical models, no clinical studies have yet targeted these RCD modes in human CKD. The review summarizes recent advances in our understanding of RCD pathways in CKD, looks at inter-relations between the pathways (with the emphasis on propagation of death signals) and the evidence for therapeutic targeting of molecules in the RCD pathways to prevent or treat CKD.
IGF-1 levels in the general population, heart failure patients, and individuals with acromegaly: differences and projections from meta-analyses—a dual perspective
Authors: Hu Yan , Jiang Yinling , Duan Lixia , Yang Songwei , Tuniyazi Subinur , Zou Jianghua , Ma Rui , Muhemaitibieke Gulina , Amuti Xiayidanguli , Guo Yanying 
Published: October 2024

BackgroundThe complex relationship between insulin-like growth factor 1 (IGF-1) levels and heart failure (HF) is not fully understood, particularly across different populations and conditions. This meta-analysis aims to elucidate the dual perspectives of IGF-1 levels in the general population, HF patients, and individuals with treatment-naïve acromegaly, highlighting IGF-1 as a biomarker and potential therapeutic target in HF management.MethodsStudies were searched across multiple electronic databases up to January 2024 and independently identified by reviewers. The outcomes were analyzed using RevMan 5.4 and STATA 15.ResultsA total of 25 articles were ultimately included in the analysis. Six studies compared IGF-1 levels between HF patients and non-HF controls, revealing significantly lower IGF-1 levels in HF patients (mean difference −20.93; 95% CI −37.88 to −3.97; p = 0.02). This reduction was consistent across various HF subtypes and severities. In addition, individuals with intermediate IGF-1 levels had a lower risk of developing HF [risk ratio (RR) 0.78; 95% CI 0.74–0.83; p &lt; 0.01] and HF-related mortality (RR 0.98; 95% CI 0.97, 0.99; p &lt; 0.01) compared to those with low IGF-1 levels, suggesting a protective role for maintaining adequate IGF-1 levels. Conversely, treatment-naïve acromegaly patients, characterized by excessively high IGF-1 levels, showed a significantly higher incidence of both diastolic HF [odds ratio (OR) 9.08; 95% CI 6.20–13.29; p &lt; 0.01] and systolic HF (OR 13.1; 95% CI 6.64–25.84; p &lt; 0.01), implicating supraphysiological IGF-1 levels in adverse cardiac outcomes.ConclusionsOur meta-analysis highlights the complex interplay between IGF-1 levels and HF. We found that reduced IGF-1 levels are commonly observed in HF patients and are associated with an increased risk of HF and higher HF-related mortality. Conversely, excessively high levels, as observed in acromegaly, are linked to a higher incidence of HF. Based on these results, it is recommended that cardiac function be closely monitored in patients with reduced IGF-1 levels and in those with acromegaly. These findings suggest that IGF-1 could hold potential prognostic value for risk stratification in HF.
Examining and comparing the relation between representational competence and conceptual knowledge across four samples
Authors: Edelsbrunner Peter Adriaan , Hofer Sarah Isabelle 
Published: October 2024

IntroductionWhereas it is commonly assumed that in learning science, representational competence is a critical prerequisite for the acquisition of conceptual knowledge, comprehensive psychometric investigations of this assumption are rare. We undertake a step in this direction by re-analyzing the data from a recent study that found a substantial correlation between the two constructs in undergraduates in the context of field representations and electromagnetism.MethodsIn this pre-registered contribution, we re-analyzed the data (N = 515 undergraduate students; Mage = 21.81, SDage = 4.04) to examine whether the relation between representational competence and conceptual knowledge, both measured with psychometrically validated test instruments, is similar or varies between four samples from two countries. To this end, we employed correlational analysis and scatter plots. Employing these methods, we examined whether a positive relation between representational competence and conceptual knowledge can be found and is of similar magnitude in all samples. We also employed multiple-group latent profile analysis to examine how the more detailed association between the two constructs varies or is similar across samples.ResultsWe found that the relation between the two constructs was positive in all four samples, but was stronger in the samples consisting primarily of engineering and physics students than in environmental sciences and teacher education-students. All latent profiles indicated that high representational competence is a prerequisite for high conceptual knowledge, but not vice versa. We found little relation to learners’ gender and topic-specific learning opportunities in high school.DiscussionThese results indicate that the qualitative findings of a positive relation between representational competence and conceptual knowledge, with no evidence of learners that achieve high conceptual knowledge with low representational competence, generalize across different populations. We derive hypotheses for further moderating factors that can be examined in future research.
Comparative efficacy, toxicity, and insulin-suppressive effects of simvastatin and pravastatin in fatty acid-challenged mouse insulinoma MIN6 β-cell model
Authors: Arefanian Hossein , Sindhu Sardar , Al-Rashed Fatema , Alzaid Fawaz , Al Madhoun Ashraf , Qaddoumi Mohammed , Bahman Fatemah , Williams Michayla R. , Albeloushi Shaima , Almansour Nourah , Ahmad Rasheed , Al-Mulla Fahd 
Published: October 2024

IntroductionFamilial hypercholesterolemia, the highly prevalent form of dyslipidemia, is a well-known risk factor for premature heart disease and stroke worldwide. Statins, which inhibit 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase, are the first-choice treatment for dyslipidemias, and have been effective in reducing the risk of stroke and myocardial infarction. However, emerging evidence indicates that statins may increase the incidence of new-onset type 2 diabetes by reducing β-cell mass and function. Notably, past in vitro reports studying the effects of statins on β-cells were performed without including free fatty acids in the model. This factor should have been addressed since these agents are used to treat individuals with hyperlipidemia.MethodsHere, we used a mouse insulinoma MIN6 β-cell culture model to assess the efficacy, cytotoxicity, and insulin-suppressive effects of simvastatin and pravastatin in the presence of palmitic, linoleic, and oleic acids cocktail to mimic mixed lipids challenge in a biologically relevant setting.Results and discussionOur findings indicate that simvastatin was more effective in lowering intracellular cholesterol but was more cytotoxic as compared to pravastatin. Similarly, simvastatin exhibited a higher suppression of total insulin content and insulin secretion. Both drugs suppressed insulin secretion in phases 1 and 2, dose-dependently. No significant effect was observed on mitochondrial respiration. More importantly, elution experiments showed that insulin content diminution by simvastatin treatment was reversible, while exogenous mevalonate did not improve total insulin content. This suggests that simvastatin's influence on insulin content is independent of its specific inhibitory action on HMG-CoA reductase. In conclusion, our study identified that simvastatin was more effective in lowering intracellular cholesterol, albeit it was more toxic and suppressive of β-cells function. Notably, this suppression was found to be reversible.
How do higher education policies influence the shaping of sustainable development values in China: a three-dimensional framework
Authors: Wei Changwei , Chen Jiali 
Published: October 2024

IntroductionIn the face of global challenges, higher education is regarded as an important force to promote the achievement of the 2030 Sustainable Development Goals (SDGs). Existing research has focused on articulating and analyzing the impact of value shaping for sustainable growth in higher education, although articulation and systematic analysis of higher education policy remain lacking.MethodsBased on the policy tool perspective, this paper constructed a three-dimensional analysis framework by using content analysis and the PMC index model to undertake a thorough analysis of higher education policies published at the central level in China from 2009 to 2024.ResultsThis study found that current higher education policies had multiple impacts on the formation of sustainable development values: (1) In the four dimensions of sustainable development proposed by the United Nations, China's higher education policy had shown clear guiding ideology and action direction; (2) In shaping sustainable values, China's higher education policies showed clear progress in three key dimensions; (3) The value and innovation of this study in shaping the values of sustainable development in higher education policies were primarily expressed in the following aspects.DiscussionThis paper suggested a way for optimizing the design of China's higher education policies, providing empirical data and theoretical support for China's higher education policies to better promote the ideals of sustainable development.
Candida albicans infection model in Drosophila melanogaster suggests a strain-specific virulent factor boosting a stormy innate immune response
Authors: Cortacans Mariona , Arch Marta , Fuentes Esther , Cardona Pere-Joan 
Published: October 2024

IntorductionPathogens drive the evolution of host defence strategies, with both innate and adaptive immune systems playing key roles. Priming enhances the innate immune system’s readiness by functionally reprogramming immune cells after initial exposure to stimuli, like β-glucans. In this sense, Drosophila melanogaster is a valuable model to evaluate the role of innate immunity to control infections.ObjectivesIn this study we aimed to set light on the immune priming effect of oral treatment with heat-killed M. manresensis and two different heat-killed C. albicans isolates upon systemic infection by C. albicans in the D. melanogaster model.MethodsA clinical and a control ATCC 90028 Candida albicans strain were used. Flies were primed through oral administration of heat-killed C. albicans (hkCa), both clinical and control, and hk-Mycolicibacterium manresensis. After priming, flies were systemically infected with both C. albicans isolates. Host survival, pathogen load, and immune response in response to treatment and infection were evaluated.ResultsBoth treatments showed a significant capacity to enhance the expression of antimicrobial peptides, in particular Diptericin, and Drosomycin in males. This response had a marked sexual dimorphism due to the difference in Upd3, Nox, and Duox expression. Surprisingly, even when priming was able to avoid the growth of both C. albicans strains, survival was not improved in the case of the clinical isolate, causing an unexpected mortality rate in hours, regardless of the host’s sex. Gene expression analysis 24 hours post-infection showed an exacerbated increase in Diptericin, Drosomycin and Upd3 expression upon infection with the clinical strain.ConclusionData herein suggests the presence of a strain-specific component in C. albicans as the booster of a “stormy” innate immune response, which must be further investigated, and position D. melanogaster as a useful model for evaluating virulent factors related to the modulation of the innate immunity.
Case report: Partial regression of metastatic squamous cell carcinoma with altered azathioprine dosage after long-term use in renal transplant patient
Authors: Ormston Tegan , Da Gama Duarte Jessica , Quigley Luke T. , Jackett Louise , Whitlam John , Behren Andreas , Gyorki David E. 
Published: October 2024

IntroductionWe report the partial regression of metastatic squamous cell carcinoma (SCC) after reduction of long-term azathioprine therapy while awaiting surgery. The patient was a 69-year-old man with a history of kidney transplantation. Moderately differentiated SCC arising in the anterior neck was initially diagnosed, followed later by poorly differentiated SCC metastases to cervical lymph nodes. Lymph node clearance was performed 28 days after a reduction in azathioprine dosage. The palpable lymph node lesion had noticeably decreased in size at the time of surgery, and subsequent histology only detected 7mm and 0.2mm deposits of poorly differentiated SCC in 2 of 5 level I nodes, and a further 10 reactive nodes from levels II and III. One positive level I and another benign level II/III node, demonstrated necrosis, histiocytic infiltration and fibrosis, interpreted as features of regression. Hence, we investigated the role of immune cells in the partial regression of metastatic SCC after reduction of long-term azathioprine therapy while awaiting surgery.MethodsMultispectral immunohistochemistry using custom markers was performed on regions of interest of excised cervical lymph nodes, encompassing the entire SCC deposit and the surrounding adjacent stroma to quantify to number and types of immune cells present.ResultsMultispectral immunohistochemistry revealed the heavy infiltration of activated T cells in the tumour, as well as PD-L1+ antigen-presenting cells in the surrounding adjacent stroma, suggesting an immunologically mediated partial regression.DiscussionWe hypothesize that this reaction was triggered by azathioprine dose reduction. Dose modification of long-term immunosuppressive medications in patients with a transplantation history who later develop SCCs warrants further investigation.
Insights into the historical trajectory and research trends of immune checkpoint blockade in colorectal cancer: visualization and bibliometric analysis
Authors: Chang Yonglong , Zhou Xuhui , Nie Kechao , Liu Jinhui , Zhang Sifang 
Published: October 2024

BackgroundColorectal cancer (CRC) is a malignant tumor that poses a significant threat to human health due to rising incidence and mortality rates. In recent years, immune checkpoint blockade (ICB) therapy, represented by Programmed death receptor 1 (PD-1), T-lymphocyte-associated protein 4 (CTLA-4), and others, has been widely applied in CRC and has achieved encouraging results in some patients and has become a hot topic in both clinical and basic research.ObjectiveThis study undertakes a comprehensive bibliometric analysis of ICB research in CRC, aiming to evaluate the current status, identify future trends, and provide scientific insights for researchers and decision-makers.MethodsUtilizing the Web of Science Core Collection (WoSCC), articles focusing on ICB in CRC from 2000 to 2022 were retrieved. Knowledge mapping and bibliometric analysis were conducted using tools such as CiteSpace, VOSviewer, SCImago Graphicay, and the R package bibliometrix.Results6,718 publications were analyzed from 24,846 institutions across 639 regions. Temporally, ICB research in CRC is rapidly advancing, led by the USA and China with extensive global collaborations. Sun Yat-sen University from China stands out as the institution with the highest number of publications. Professor Thierry Andre from Sorbonne University in France is identified as a prolific author in this field, engaging in extensive collaboration for clinical trials on a global scale. Publications related to this research topic were published in 1,142 academic journals, demonstrating a positive co-citation relationship. Key clustering and burst terms analysis indicate that current research on ICB in CRC has shifted from basic experiments to clinical trials and from universal healthcare to precision medicine.ConclusionICB therapies have shown substantial progress in CRC, highlighting their therapeutic potential. Research trends emphasize deeper drug mechanisms, treatment efficacy prediction, managing immune-related adverse events, and exploring novel drug delivery methods. Collaboration across borders remains crucial for further advancements.
Effect of tea consumption on the development of hypertension, diabetes, and obesity: a bidirectional two-sample Mendelian randomization analysis
Authors: Li Xueying , Zhang Congcong , Weng Yihui , Yu Weiming , Cai Xianlei 
Published: October 2024

BackgroundThe effect of tea consumption on conditions such as hypertension, diabetes, and obesity has attracted significant global interest. However, the results of various studies on this topic have been mixed and somewhat contentious. Therefore, we conducted a Mendelian randomization (MR) analysis to investigate the causal relationships between tea consumption and the aforementioned health conditions.MethodsA bidirectional two-sample MR analysis was used to systematically explores the associations between tea consumption and hypertension, diabetes, and obesity. MR-Egger regression, weighted median, inverse variance weighted, and weighted mode methods were used to evaluate the potential causal associations. Leave-one-out sensitivity test was used to check the robustness of the IVW estimates.ResultsMR analysis indicated that genetically predicted tea consumption is associated with a protective effect against hypertension, with an odds ratio (OR) of 0.78 and a 95% confidence interval (CI) ranging from 0.64 to 0.95. Additionally, tea consumption appeared to have a potential protective effect on type 2 diabetes and obesity related to excessive calorie intake, influenced by specific single nucleotide polymorphisms (SNPs), namely “rs57462170” and “rs17685.” No causal link was observed between the consumption of green or herbal tea and hypertension, diabetes, or obesity. However, there was a marginal negative association between type 2 diabetes and tea consumption and (OR = 0.99; 95% CI: 0.97–1.00) and a significant negative correlation between obesity due to excessive calorie intake and green tea consumption (OR = 0.35; 95% CI: 0.16–0.78).ConclusionThis study demonstrates a protective causal relationship between the consumption of tea (including black and green teas) and reduced risk of hypertension. Furthermore, our results suggest that tea intake may also have a protective effect on type 2 diabetes and obesity. The results recommend further research to verify or refine these findings.
High barley intake in non-obese individuals is associated with high natto consumption and abundance of butyrate-producing bacteria in the gut: a cross-sectional study
Authors: Maruyama Satoko , Matsuoka Tsubasa , Hosomi Koji , Park Jonguk , Murakami Haruka , Miyachi Motohiko , Kawashima Hitoshi , Mizuguchi Kenji , Kobayashi Toshiki , Ooka Tadao , Yamagata Zentaro , Kunisawa Jun 
Published: October 2024

ObjectiveBarley, abundant in β-glucan, a soluble dietary fiber, holds promise in obesity prevention. Given the microbial metabolism of dietary fiber in the gastrointestinal tract, we investigated the role of gut microbiota in non-obese individuals consuming high levels of barley.MethodsOur study enrolled 185 participants from “The cohort study on barley and the intestinal environment (UMIN000033479).” Comprehensive physical examinations, including blood tests, were conducted, along with separate assessments of gut microbiome profiling and dietary intake. Participants were categorized into high and low barley consumption groups based on the median intake, with non-obese individuals in the high intake group identified as barley responders while participants with obesity were designated as non-responders. We compared the relative abundance of intestinal bacteria between these groups and used multivariate analysis to assess the association between intestinal bacteria and barley responders while controlling for confounding factors.Results and discussionAmong the fermented food choices, responders exhibited notably higher consumption of natto (fermented soybeans) than non-responders. Moreover, after adjusting for confounders, Butyricicoccus and Subdoligranulum were found to be significantly more prevalent in the intestines of responders. Given natto’s inclusion of Bacillus subtilis, a glycolytic bacterium, and the butyrate-producing capabilities of Butyricicoccus and Subdoligranulum, it is hypothesized that fiber degradation and butyrate production are likely to be enhanced within the digestive tract of barley responders.
Development and validation of a tumor marker-based model for the prediction of lung cancer: an analysis of a multicenter retrospective study in Shanghai, China
Authors: Hu Sheng , Guo Qiang , Ye Jiayue , Ma Hongdan , Zhang Manyu , Wang Yunzhe , Wan Bingen , Qiu Shengyu , Liu Xinliang , Luo Guiping , Zhang Wenxiong , Yu Dongliang , Xu Jianjun , Wei Yiping , Zeng Linxiang 
Published: October 2024

BackgroundThe incidence and mortality rates of cancer are the highest globally. Developing novel methodologies that precisely, safely, and economically differentiate between benign and malignant lung conditions holds immense clinical importance. This research seeks to construct a predictive model utilizing a combination of diverse biomarkers to effectively discriminate between benign and malignant lung diseases.MethodsThis retrospective study included patients admitted to the two general hospitals in Shanghai from 2014 to 2015. This study was developed using five tumor markers: carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), cytokeratin fragment 21-1 (CA211), squamous cell carcinoma antigen (SCC), and neuron specific enolase (NSE). The entire sample was divided into two groups according to the hospital: 1033 cases were included in the development cohort and 300 cases in the validation cohort. Logistic regression analysis was used for univariate analysis to explore individual correlations between each selected clinical variable and lung cancer diagnostic outcome. Diagnostic prediction models were constructed and validated based on independent prognostic factors identified using multifactorial analysis. A nomogram was created using these tumor markers (age and sex were additionally included) and validated using the concordance index and calibration curves. Clinical prediction models were evaluated using decision curve analysis.ResultsFully adjusted multivariate analysis showed that the risk of lung cancer was 2.38 times higher in men than in women. CEA positivity was associated with an 13.41-fold increased risk in lung cancer. The area under the curve (AUC) values for the development cohort and validation cohort models were 0.907 and 0.954, respectively. In the established nomogram, the AUC for the receiver operating characteristic curve was 0.907 (95% CI, 0.889–0.925). The validation model confirmed the strong discriminative power of the nomogram (AUC = 0.954). The described calibration curves demonstrated good fit predictions and observation probabilities. In addition, decision curve analysis concluded that the newly established nomogram has important implications for clinical decision making.ConclusionsCombined prediction models based on CEA, CA199, CA211, SCC, and NSE biomarkers could significantly the differentiation between benign and malignant lung diseases, thus facilitating better clinical decision making.