bluuebunny/crossref_metadata_2025_split huggingface dataset:
LncRNAH19 acts as a ceRNA of let-7g to facilitate EndMT in hypoxic pulmonary hypertension via regulating TGF-β signalling pathway
Authors: Yu xin , Huang Jiabing , Liu Xu , Li Juan , Yu Miao , Li Minghui , Xie Yuliang , Li Ye , Qiu Junyu , Xu Zhou , Zhu Tiantian , Zhang Weifang 
Published: May 2024

Abstract

Background
Hypoxic pulmonary hypertension (HPH) is a challenging lung arterial disorder with remarkably high incidence and mortality rates, and the efficiency of current HPH treatment strategies is unsatisfactory. Endothelial-to-mesenchymal transition (EndMT) in the pulmonary artery plays a crucial role in HPH. Previous studies have shown that lncRNA-H19 (H19) is involved in many cardiovascular diseases by regulating cell proliferation and differentiation but the role of H19 in EndMT in HPH has not been defined.
Methods
In this research, the expression of H19 was investigated in PAH human patients and rat models. Then, we established a hypoxia-induced HPH rat model to evaluate H19 function in HPH by Echocardiography and hemodynamic measurements. Moreover, luciferase reporter gene detection, and western blotting were used to explore the mechanism of H19.
Results
Here, we first found that the expression of H19 was significantly increased in the endodermis of pulmonary arteries and that H19 deficiency obviously ameliorated pulmonary vascular remodelling and right heart failure in HPH rats, and these effects were associated with inhibition of EndMT. Moreover, an analysis of luciferase activity indicated that microRNA-let-7g (let-7g) was a direct target of H19. H19 deficiency or let-7g overexpression can markedly downregulate the expression of TGFβR1, a novel target gene of let-7g. Furthermore, inhibition of TGFβR1 induced similar effects to H19 deficiency.
Conclusions
In summary, our findings demonstrate that the H19/let-7g/TGFβR1 axis is crucial in the pathogenesis of HPH by stimulating EndMT. Our study may provide new ideas for further research on HPH therapy in the near future.
IQI-UNet: A Robust Gaussian Noise Removal in Image Quality Improvement]{IQI-UNet: A Robust Gaussian Noise Removal in Image Quality Improvement
Authors: AMMAR Sonda , Kchaou Amina , Hamed Bassem Ben 
Published: May 2024

Abstract

Image quality enhancement is a rapidly advancing field in computer vision, with researchers exploring various techniques. This paper introduces a robust Gaussian noise removal, denoted as IQI-UNet, based on the U-Net deep learning architecture, which excels in image denoising. The key advantage of our model is its ability to operate without a reference image or prior knowledge of the application context. Our study investigates the impact of incorporating additional blocks into the autoencoder, resulting in an optimized architecture. The performance of the proposed IQI-UNet model is evaluated against twelve well-known methods using three datasets, namely Set5, Set14, and CBSD68. The proposed model demonstrates superior performance compared to established methods, achieving a remarkable 43% improvement in PSNR and a 29% improvement in SSIM. Furthermore, we introduce Shannon entropy as a metric to assess both the quantity and the quality of retained data. The evaluation, conducted on benchmark datasets, reaffirms the efficacy of IQI-UNet in enhancing image quality. The outcomes are highlighted by statistical tests, which implies that the obtained results are statistically significant.
Assessing the Effectiveness of Case-Based Learning and Concept Mapping Approaches in Developing Theoretical and Metacognitive Skills in Medical Students
Authors: Çetinkaya Levent 
Published: May 2024

Abstract

This research utilizes a mixed-method approach, integrating quasi-experimental design and quantitative triangulation methods to determine the impact of Case-Based Learning (CBL) and CBL supported by Concept Maps (CMs) on the theoretical knowledge comprehension abilities and metacognitive skills of medical students. In the first phase of the two-stage evaluation process, researchers administered a pre-test/post-test achievement test focusing on students' comprehension levels of theoretical knowledge; the data were analyzed using two-way ANOVA. The analysis results indicated a statistically significant increase in the average achievement scores across all learning environments; however, it was determined that this increase was not attributable to differences specific to the learning environments. In the second phase of the assessment, a new test was administered to not only assess the students' theoretical knowledge but also how they apply this knowledge in new and uncertain situations. The data obtained from this test, which targeted students' metacognitive skills and was administered after the experimental process, were analyzed using One-Way ANOVA to determine the effectiveness of the learning environments. The analysis results revealed that CBL significantly impacts metacognitive skills, and this effect is enhanced when supported by CMs. The findings demonstrate that CBL and CMs-supported educational approaches play a significant role in enhancing medical students' ability to effectively apply theoretical knowledge in the face of new and uncertain situations. These findings highlight the extensive utility of CBL and CM-supported approaches in enhancing critical metacognitive skills, essential for medical education. Furthermore, they suggest practical ways for integrating these methodologies into future curricula and refining educational strategies.
Cellular senescence induced by cholesterol accumulation is mediated by lysosomal ABCA1 in APOE4 and AD
Authors: Wang Shaowei , Li Boyang , Cai Zhiheng , Hugo Cristelle , Li Jie , Sun Yi , Qian Lu , Remaley Alan T. , TCW Julia , Chui Helena C. , Bennett David A. , Arvanitakis Zoe , Kerman Bilal , Yassine Hussein 
Published: May 2024

Abstract

Background
Cellular senescence is a hallmark of aging and has been implicated in Alzheimer’s disease (AD) pathogenesis. Cholesterol accumulation drives cellular senescence; however, the underlying mechanisms are unclear. ATP-binding cassette transporter A1 (ABCA1) plays an important role in cholesterol homeostasis. ABCA1 expression and its trafficking is altered in APOE4 and AD cellular and mouse models. However, whether ABCA1 trafficking is involved in cellular senescence in APOE4 and AD remains unknown.
Methods
We examined the association between cellular senescence and ABCA1 expression in human postmortem brain samples using transcriptomic, histological, and biochemical analyses. An unbiased proteomic screening was performed to identify targets that mediate cellular ABCA1 trafficking. APOE4-TR mice, immortalized, primary and induced pluripotent stem cell (iPSC) models were used to examine the cholesterol-ABCA1-senescence pathways.
Results
Bulk and single nuclei transcriptomic profiling of the human dorsolateral prefrontal cortex from the Religious Order Study/Memory Aging Project (ROSMAP) revealed upregulation of cellular senescence transcriptome signatures in AD, which was strongly correlated with ABCA1 expression. Immunofluorescence and immunoblotting analyses confirmed increased ABCA1 expression in AD brain tissues, which was associated with lipofuscin-stained lipids and mTOR phosphorylation. Using discovery proteomics, caveolin-1, a sensor of cellular cholesterol accumulation, was identified to promote ABCA1 endolysosomal trafficking. Greater caveolin-1 expression was found in both APOE4-TR mouse models and AD human brains. Cholesterol induced mTORC1 activation was regulated by ABCA1 expression or its lysosomal trapping. Reducing cholesterol by cyclodextrin in APOE4-TR mice reduced ABCA1 lysosome trapping and increased ABCA1 recycling to efflux cholesterol to HDL particles, reducing mTORC1 activation and senescence-associated neuroinflammation. In human iPSC-derived astrocytes, the reduction of cholesterol by cyclodextrin attenuated inflammatory responses.
Conclusions
Cholesterol accumulation in APOE4 and AD induced caveolin-1 expression, which traps ABCA1 in lysosomes to activate mTORC1 pathways and induce cellular senescence. This study provided novel insights into how cholesterol accumulation in APOE4 and AD accelerates senescence.
Fast anion reorientations in ammine yttrium borohydride compounds Y(BH4 )3 ·xNH3 (x = 3 and 7): a nuclear magnetic resonance study
Authors: Babanova O. A. , Skoryunov R. V. , Soloninin A. V. , Skripov A. V. 
Published: May 2024

Abstract

The ammine borohydride compounds Y(BH4)3·xNH3 belong to the emerging class of materials, where the application-relevant properties can be tuned by introducing neutral NH3 ligands. To study the dynamical properties of Y(BH4)3·3NH3 and Y(BH4)3·7NH3, we have measured the 1H and 11B nuclear spin-lattice relaxation rates and nuclear magnetic resonance (NMR) spectra in these compounds over a wide temperature range (6–298 K). Our measurements have revealed that both compounds retain the unusually high reorientational mobility of BH4− anions down to low temperatures. In particular, for the fastest BH4 reorientational process, the corresponding H jump rate is of the order of 108 s− 1 near 96 K in Y(BH4)3·3NH3 and near 33 K in Y(BH4)3·7NH3. The fast reorientational motion of BH4− anions is discussed in terms of the coordination environment of BH4 groups in Y(BH4)3·xNH3.
Metabolic stress-induced dysregulation of the Hippo signaling pathway inhibits the occurrence of hepatocarcinoma
Authors: Li Ziyi , Tao Qianqian , Jing Wenshan , Lu Xingyang , Zhang Qi , Hu Gaobin , Huang Long , Zhang Liangliang , Peng Hui , Feng Qiyu , Yu Qinsheng 
Published: May 2024

Abstract

Liver fibrosis is the natural stress response of the liver to injury and a critical intermediate stage in the progression of most liver diseases. Here, we first demonstrated via a retrospective clinical study that the incidence of advanced hepatocellular carcinoma (HCC) was significantly higher in patients infected with hepatitis B virus (HBV) than in those with hepatolenticular degeneration (HLD). Further analyses involving miRNA and proteomics were conducted to investigate the distinct mechanisms underlying liver fibrosis induced by HBV and HLD. Results showed significant changes in metabolic pathways and molecules, especially in AMPK and Hippo signaling pathways, which play crucial roles in cellular glucose and lipid metabolism. Characteristic of HLD is a mutation/deletion in the ATPase Copper Transporting Beta (ATP7B) gene. Subsequent studies indicated that the knockdown or overexpression of ATP7B mutants activates the AMPK and Hippo signaling pathways, resulting in the inhibition of proliferation and transformation of HCC cells. AMPK phosphorylation indicates the presence of metabolic stress. Thus, this finding might partly explain why patients with HLD-related liver fibrosis are more likely to develop liver failure rather than HCC, providing new insights into the intricate mechanisms linking metabolic orchestration and tumor development.
Ethyl 2,2-difluoro-2-(2-oxo-2H-chromen-3-yl) acetate inhibits the malignant biological behaviors of colorectal cancer by restricting the phosphorylation and nuclear translocation of STAT3
Authors: LIN JIE , LIU Weijing , LI Xiaodan , LIN Jiansuo , FANG Xuehong , LIANG Yanwen , ZHANG Wen , REN Jianwei , WAGN Feng , ZOU Liyi , LIU Yi 
Published: May 2024

Abstract

To investigate the effect of a novel coumarin derivative, ethyl 2,2-difluoro-2 - (2-oxo-2H-chromen-3-yl) acetate (C2F), on the malignant biological behaviors of colorectal cancer (CRC) and elucidate its mechanism. In vitro, the effects of C2F on the proliferation, apoptosis, migration, invasion, and cell cycle of CRC cells were analyzed by MTT assay, EdU stainning, colony formation assay, flow cytometry, wound healing and transwell assay. The anti-CRC activity of C2F was evaluated in a nude mice xenograft model in vivo. Western blot was conducted to detect the expression of protein in cells and mice tissue. Then, the potential targets of C2F in CRC were predicted by network pharmacology analysis and molecular docking. The localization of STAT3 was observed through immunofluorescence experiment. C2F inhibits CRC cell proliferation, promotes CRC cell apoptosis, hinders CRC cell migration and invasion, and prevents the cell cycle from entering the G2/M phase. In vivo, C2F inhibited tumor growth in xenograft model. C2F inhibited signal transduction and activator of transcription 3 (STAT3) phosphorylation and blocked interleukin-6 (IL-6)-induced STAT3 nuclear translocation. C2F inhibits the malignant biological behavior of CRC by limiting STAT3 phosphorylation and entry into the nucleus.
Predicting colorectal cancer liver metastases histological growth patterns: inflammation on the primary tumor is associated with desmoplastic growth pattern
Authors: Abrantes Ana Margarida , Oliveira Rui Caetano , Oliveiros Bárbara , Cipriano Maria Augusta , Tralhão José Guilherme 
Published: May 2024

Abstract

Background: More than 50% of patients diagnosed with colorectal cancer (CRC) will develop liver metastases (CRCLM), which is the main cause of death for more than 60% of these patients. The aim of this study was to correlate the clinical and pathological characteristics of the primary CRC and CRCLM, with emphasis in predicting the histological growth pattern of the CRCLM.
Methods: Cohort of seventy-three patients with CRC. Analysis of clinical data and blinded pathological review was performed related with primary tumor and CRCLM features. The analysis was performed in SPSS (version 27) with a significance level of 5%.
Results: A statistically significant association was found between tumor size and metastasis growth pattern (p=0.002), with larger tumors giving rise to metastases with a non-desmoplastic growth pattern. Lymphovascular invasion (LVI) was associated with metachronous CRCLM (p=0.043). In the absence of LVI, the time required for CRCLM to appear was significantly longer (p=0.011). The number of metastases was significantly higher (p=0.049) in tumors without LVI when compared to tumors with LVI. There was a statistically significant association between CRC high-grade inflammation and the desmoplastic metastases growth pattern of the CRCLM (p= 0.017).
Conclusion: The possibility of predicting the CRCLM histological growth pattern resorting to primary CRC characteristics would be useful for proper patient selection for surgery and adapting biological therapies.
CTCF regulates SFPQ to promote cancerous progression of osteosarcoma
Authors: 仲 新宇 , Li Dapeng , zheng Qiping , Mao Lianghao , Jiang Pan , YIN Zhengyu 
Published: May 2024

Abstract

CCCTC-binding factor (CTCF) is a candidate tumor regulatory gene encoding multifunctional transcription factors, but its role and related mechanisms in osteosarcoma are still unclear. Studies have found that SFPQ plays an oncogenic role in OS. This study aimed to clarify the transcriptional regulation of SFPQ by CTCF in osteosarcoma, and the effect of CTCF regulation of SFPQ expression on the proliferation, migration, and invasion of osteosarcoma cells. The potential transcription factor of SFPQ was identified as CTCF by the online transcription factor analysis website and UCSC database. qRT-PCR and WB are two techniques used to detect the expression level of CTCF in osteosarcoma cell lines. The regulatory relationship between CTCF and SFPQ in osteosarcoma cell lines and their common influence on the biological behavior of osteosarcoma cells were investigated by cell function test, double luciferase report test, and rescue test.UCSC and GEPIA2 databases identified CTCF as a potential transcription factor of SFPQ, and there was a moderate correlation between them. qRT-PCR and WB experiments showed that CTCF was highly expressed in osteosarcoma cell lines. After overexpression of CTCF in osteosarcoma cell lines, the proliferation, migration, and invasion of osteosarcoma cells were enhanced. CTCF can bind to the promoter sequence of SFPQ and enhance its expression level. Rescue experiments showed that overexpression of CTCF could reduce the inhibition of SFPQ knockdown on the proliferation, migration, and invasion of osteosarcoma cell lines. CTCF plays a carcinogenic role in osteosarcoma. As a transcriptional activator of SFPQ, CTCF positively regulates and promotes the expression of SFPQ, and increases the osteosarcoma cells' malignant biological behavior.
Predict progression free survival and overall survival using objective response rate for anti - PD1 / PDL1 therapy development
Authors: Yang Lei , Raveendran Geethanjali , Meng Xiang , Lin Ji , Meng Zhaoling 
Published: May 2024

Abstract

Background: In anti - PD1 (programmed death-1) / PDL1 (programmed death ligand 1) therapy development for solid tumors, the objective response rate (ORR) is a commonly used clinical endpoint for early phase study decision making, while progression free survival (PFS) and overall survival (OS) are widely used for late phase study decision making. Developing predictive models for median PFS (mPFS) and median OS (mOS) based on early phase clinical outcome ORR could inform late phase study design optimization and probability of success (POS) evaluation. In the existing literature, there are ORR / mPFS / mOS associations and surrogacy investigations with limited number of included clinical trials. In this paper, without establishing surrogacy, we attempt to predict mPFS and mOS based on early efficacy in ORR and to optimize late phase trial design for anti - PD1 / PDL1 therapy development.
Methods: In order to include an adequate number of eligible clinical trials, we built a comprehensive clinical trial quantitative landscape database (QLD) by combining information from different sources, such as clinicaltrial.gov, publications, company press releases for relevant indications and therapies. We developed a generalizable algorithm to systematically extract structured data and manual curation for scientific accuracy and completeness. More than 150 late phase clinical trials were identified for ORR / mPFS (ORR / mOS) predictive model development, while existing literature included at most 40 trials. A tree-based machine learning regression model was derived to account for ORR / mPFS (ORR / mOS) relationship heterogeneity across tumor type, stage, line of therapy, treatment class and borrow strength simultaneously when homogeneity persists.
Results: The proposed method ensures that the predictive model is robust and has explicit structure for clinical interpretation. Over 1000 times cross validation, the average predictive mean square error of the proposed model is competitive to random forest and extreme gradient boosting methods and outperforms commonly used additive or interaction linear regression models.
Conclusions: An example application of the proposed ORR / mPFS (ORR / mOS) predictive model on late phase trial POS evaluation for anti - PD1 / PDL1 combination therapy was illustrated.
Evaluating the Merits of an Integrated Medical Education Approach and Multidisciplinary Diagnostics in Continuing Medical Education for Complex Hepatic Diseases
Authors: Ren Shan , Zheng Sujun , Chen Xinyue 
Published: May 2024

Abstract

Background: This study explores the value of applying integrated medical education and the multidisciplinary diagnostic treatment mode in continuing clinical education for complex liver diseases.
Methods: A total of 62 resident and continuing education doctors from the the first Department of Liver Disease Center, Beijing You'an Hospital, Capital Medical University, were selected as the subjects of this study. They were randomly divided into an experimental group (integrated medical education and multidisciplinary diagnostic treatment) and a traditional teaching group. The former used a teaching model guided by problems, centered on real cases, and multidisciplinary consultation, while the latter adopted traditional teaching combined with clinical rotation and mini-lectures. In the end, the training effects of three teaching methods, namely, the accurate rate of medical record analysis, job competence, and self-evaluation of teaching effects, were adopted.
Results: The experimental group scored higher than the traditional teaching group in terms of the accuracy rate of liver disease case analysis, patient management and decision-making, professional knowledge and skills, and learning ability. The differences were statistically significant (P<0.05). Compared with the traditional teaching group, after the experimental group completed training based on integrated medical education and multidisciplinary diagnostic treatment mode, the scores on the self-evaluation questionnaire (stimulating interest in learning, enhancing problem analysis ability, helping to understand, remember theoretical knowledge, expanding clinical thinking, activating class atmosphere, and hoping to continue this teaching mode) were better than those in the traditional classroom group, and the differences were statistically significant (P<0.05).
Conclusion: Training based on integrated medical education and multidisciplinary diagnostic treatment mode can improve the accuracy of resident doctors and continuing education doctors in diagnosing complex liver diseases, enhance their learning ability, and clinical decision-making, and increase doctor satisfaction. It has essential application value in the continuing clinical education of complex liver diseases.
α-Synuclein fibrils enhance HIV-1 infection of human T cells, macrophages and microglia
Authors: Kirchhoff Frank , Olari Lia , Liu Sichen , Arnold Franziska , Kühlwein Julia , Miró Marta Gil , Updahaya Ajeet Rijal , Stuerzel Christina , Thal Dietmar , Walther Paul , Danzer Karin , Münch Jan 
Published: May 2024

Abstract

HIV-associated neurocognitive disorders (HAND) and viral reservoirs in the brain remain a significant challenge. Despite their importance, the mechanisms allowing HIV-1 entry and replication in the central nervous system (CNS) are poorly understood. Here, we show that α-synuclein and (to a lesser extent) Aβ40 fibrils associated with neurological diseases, enhance HIV-1 entry and replication in human T cells, macrophages, and microglia. Additionally, an HIV-1 Env-derived amyloidogenic peptide accelerated amyloid formation by α-synuclein and Aβ peptides. Mechanistic studies showed that α-synuclein and Aβ40 fibrils interact with HIV-1 particles and promote virion attachment and fusion with target cells. Despite an overall negative surface charge, these fibrils facilitate interactions between viral and cellular membranes. Enhancing effects of human brain extracts on HIV-1 infection correlated with binding to Thioflavin T commonly used to stain amyloids. Our results suggest a detrimental interplay between HIV-1 and brain amyloids that may contribute to the development of neurodegenerative diseases.