bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dementia death rates prediction
Authors: Gaidai Oleg , Yakimov Vladimir , Balakrishna Rajiv 
Published: September 2023

Abstract
Background
Prevalence of dementia illness, causing certain morbidity and mortality globally, places burden on global public health. This study primary goal was to assess future risks of dying from severe dementia, given specific return period, within selected group of regions or nations.

Methods
Traditional statistical approaches do not have benefits of effectively handling large regional dimensionality, along with nonlinear cross-correlations between various regional observations. In order to produce reliable long-term projections of excessive dementia death rate risks, this study advocates novel bio-system reliability technique, that being particularly suited for multi-regional environmental, biological, and health systems.

Data
Raw clinical data has been used as an input to the suggested population-based, bio-statistical technique using data from medical surveys and several centers.

Results
Novel spatiotemporal health system reliability methodology has been developed and applied to dementia death rates raw clinical data. Suggested methodology shown to be capable of dealing efficiently with spatiotemporal clinical observations of multi-regional nature. Accurate disease risks multi-regional spatiotemporal prediction being done, relevant confidence intervals have been presented as well.

Conclusions
Based on available clinical survey dataset, the proposed approach may be applied in a variety of clinical public health applications. Confidence bands, given for predicted dementia-associated death rate levels with return periods of interest, have been reasonably narrow, indicating practical values of advocated prognostics.
Association of metabolic syndrome and its components with the risk of urologic cancers: a prospective cohort study
Authors: Jiang Runxue , Wang Xia , Li Zhi , Cai Haifeng , Sun Zhiguo , Wu Shouling , Chen Shuohua , Hu Hailong 
Published: September 2023

Abstract
Objective
To investigate the association between metabolic syndrome (MetS) and its components and the risk of developing urologic cancers.

Methods
This study included 101,510 observation subjects from May 2006 to December 2007. The subjects received questionnaires and were subjected to clinical and laboratory examinations to collect data on baseline population characteristics, waist circumference (WC), blood pressure (BP), blood glucose, blood lipids, lifestyle, and past disease history. Finally, follow-up was conducted from the date of recruitment to December 31, 2019. Cox proportional hazards modelling was applied to analyze the association between MetS and its components and the risk of developing urologic cancers.

Results
A total of 97,975 observation subjects met the inclusion criteria. The cumulative follow-up period included 1,209,178.65 person-years, and the median follow-up time was 13.03 years. During the follow-up period, 485 cases of urologic cancers (165 cases of kidney cancer, 134 cases of prostate cancer, 158 cases of bladder cancer, and 28 cases of other urologic cancers) were diagnosed. The log-rank test results for the cumulative incidences of urologic cancer, kidney cancer, and prostate cancer indicated significant (P < 0.01) differences between the MetS and non-MetS groups (0.70% vs. 0.48%, 0.27% vs. 0.15%, and 0.22% vs. 0.13%, respectively). Compared to the non-MetS group, the risk of developing urologic [HR (95% CI) = 1.29 (1.08–1.55)], kidney [HR (95% CI) = 1.74 (1.28–2.37)], and prostate [HR (95% CI) = 1.47 (1.04–2.07)] cancers was significantly higher in the MetS group. In the MetS group, elevated BP increased the risk of developing of urologic cancer [HRs (95% CI) = 1.35 (1.10–1.66)] and kidney cancer [HR (95% CI) = 1.74 (1.21–2.51)], while central obesity increased the risk of developing prostate cancer [HR (95% CI) = 1.68 (1.18–2.40)].

Conclusions
MetS increased the risk of developing urologic, kidney, and prostate cancers but had no association with the development of bladder cancer.
Satisfaction and self-confidence among nursing students with simulation learning during COVID-19
Authors: Alsadi Mohammad , Oweidat Islam , Khrais Huthaifah , Tubaishat Ahmad , Nashwan Abdulqadir J. 
Published: September 2023

Abstract
Aim
This survey aimed to investigate nursing students’ satisfaction and self-confidence in simulation in education during the COVID-19 pandemic. Along with comparing these levels based on selected students’ characteristics.

Design
A cross-sectional survey.

Methods
The survey was conducted at the faculty of nursing of a private university in Jordan. Students’ satisfaction and self-confidence levels in simulation learning were measured using the National League for Nursing (NLN) Student Satisfaction and Self-confidence in Learning Scales.

Results
A total of 138 undergraduate nursing students participated in the survey. Students’ satisfaction levels and self-confidence in simulation learning were lower (just above the scale’s midpoint) than scores reported in similar surveys. The lowest student ratings were reported as “the variety of learning activities that can be done using simulation” and “the self-confidence to develop the needed skills and knowledge to be used in real clinical settings”. The results also indicated that as students’ progress in the bachelor’s degree program, they develop higher levels of self-confidence in simulation-based learning.

Conclusions
Nursing students’ experience of simulation learning was observed to be negatively affected by the COVID-19 pandemic. High-fidelity simulation, in particular, among other simulation modalities, can be more beneficial in similar situations. Education stakeholders are invited to invest in the resources of high-fidelity simulation to maximize its benefits and help in the recovery phase after the pandemic.
Incident low muscle mass is associated with greater lung disease and lower circulating leptin in a tobacco-exposed longitudinal cohort
Authors: Zou Richard H. , Nouraie S. Mehdi , Karoleski Chad , Zhang Yingze , Sciurba Frank C. , Forman Daniel E. , Bon Jessica 
Published: September 2023

Abstract
Background
Muscle loss is prevalent in chronic obstructive pulmonary disease (COPD). Prior studies evaluating musculoskeletal dysfunction in COPD have focused on individuals with baseline low muscle mass. Currently, there is limited data evaluating clinical characteristics and outcomes associated with progression to incident low muscle mass in a tobacco-exposed cohort of individuals with baseline normal muscle mass.

Methods
We evaluated 246 participants from a single-center longitudinal tobacco-exposed cohort with serial spirometry, thoracic imaging, dual energy x-ray absorptiometry (DXA) measurements, walk testing, and plasma adipokine measurements. DXA-derived fat free mass index (FFMI) and appendicular skeletal mass index (ASMI) were used as surrogates for muscle mass. Participants with incident low muscle mass (LM) at follow-up were characterized by FFMI < 18.4 kg/m2 in males and < 15.4 kg/m2 in females and/or ASMI < 7.25 kg/m2 in males and < 5.67 kg/m2 in females.

Results
Twenty-five (10%) participants progressed to incident low muscle mass at follow-up. At baseline, the LM subgroup had greater active smoking prevalence (60% v. 38%, p = 0.04), lower FFMI (17.8 ± 1.7 kg/m2 v. 19.7 ± 2.9 kg/m2, p = 0.002), lower ASMI (7.3 ± 0.9 kg/m2 v. 8.2 ± 1.2 kg/m2, p = 0.0003), and lower plasma leptin (14.9 ± 10.1 ng/mL v. 24.0 ± 20.9 ng/mL, p = 0.04). At follow-up, the LM subgroup had higher COPD prevalence (68% v. 43%, p = 0.02), lower FEV1/FVC (0.63 ± 0.12 v. 0.69 ± 0.12, p = 0.02), lower %DLco (66.5 ± 15.9% v. 73.9 ± 16.8%, p = 0.03), and higher annual rate of FFMI decline (-0.17 kg/m2/year v. -0.04 kg/m2/year, p = 0.006). There were no differences in age, gender distribution, pack years smoking history, or walk distance.

Conclusions
We identified a subgroup of tobacco-exposed individuals with normal baseline muscle mass who progressed to incident DXA-derived low muscle mass. This subgroup demonstrated synchronous lung disease and persistently low circulating leptin levels. Our study suggests the importance of assessing for muscle loss in conjunction with lung function decline when evaluating individuals with tobacco exposure.
Sirt6 enhances macrophage lipophagy and improves lipid metabolism disorder by regulating the Wnt1/β-catenin pathway in atherosclerosis
Authors: Wang Tingting , Cheng Zheng , Zhao Ran , Cheng Jin , Ren He , Zhang Pengke , Liu Pengyun , Hao Qimeng , Zhang Qian , Yu Xiaolei , Sun Dongdong , Zhang Dongwei 
Published: September 2023

AbstractLipid metabolism disorders are considerably involved in the pathology of atherosclerosis; nevertheless, the fundamental mechanism is still largely unclear. This research sought to examine the function of lipophagy in lipid metabolism disorder-induced atherosclerosis and its fundamental mechanisms. Previously, Sirt6 has been reported to stimulate plaque stability by promoting macrophage autophagy. However, its role in macrophage lipophagy and its relationship with Wnt1 remains to be established. In this study, ApoE−/−: Sirt6−/− and ApoE−/−: Sirt6Tg mice were used and lipid droplets were analysed via transmission electron microscopy and Bodipy 493/503 staining in vitro. Atherosclerotic plaques in ApoE−/−: Sirt6−/− mice showed greater necrotic cores and lower stability score. Reconstitution of Sirt6 in atherosclerotic mice improved lipid metabolism disorder and prevented the progression of atherosclerosis. Furthermore, macrophages with Ac-LDL intervention showed more lipid droplets and increased expression of adipophilin and PLIN2. Reconstitution of Sirt6 recruited using SNF2H suppressed Wnt1 expression and improved lipid metabolism disorder by promoting lipophagy. In addition, downregulation of Sirt6 expression in Ac-LDL-treated macrophages inhibited lipid droplet degradation and stimulated foam cell formation. Innovative discoveries in the research revealed that atherosclerosis is caused by lipid metabolism disorders due to downregulated Sirt6 expression. Thus, modulating Sirt6’s function in lipid metabolism might be a useful therapeutic approach for treating atherosclerosis.
Identification of key lipid metabolism-related genes in Alzheimer’s disease
Authors: Zeng Youjie , Cao Si , Li Nannan , Tang Juan , Lin Guoxin 
Published: September 2023

Abstract
Background
Alzheimer’s disease (AD) represents profound degenerative conditions of the brain that cause significant deterioration in memory and cognitive function. Despite extensive research on the significant contribution of lipid metabolism to AD progression, the precise mechanisms remain incompletely understood. Hence, this study aimed to identify key differentially expressed lipid metabolism-related genes (DELMRGs) in AD progression.

Methods
Comprehensive analyses were performed to determine key DELMRGs in AD compared to controls in GSE122063 dataset from Gene Expression Omnibus. Additionally, the ssGSEA algorithm was utilized for estimating immune cell levels. Subsequently, correlations between key DELMRGs and each immune cell were calculated specifically in AD samples. The key DELMRGs expression levels were validated via two external datasets. Furthermore, gene set enrichment analysis (GSEA) was utilized for deriving associated pathways of key DELMRGs. Additionally, miRNA-TF regulatory networks of the key DELMRGs were constructed using the miRDB, NetworkAnalyst 3.0, and Cytoscape software. Finally, based on key DELMRGs, AD samples were further segmented into two subclusters via consensus clustering, and immune cell patterns and pathway differences between the two subclusters were examined.

Results
Seventy up-regulated and 100 down-regulated DELMRGs were identified. Subsequently, three key DELMRGs (DLD, PLPP2, and PLAAT4) were determined utilizing three algorithms [(i) LASSO, (ii) SVM-RFE, and (iii) random forest]. Specifically, PLPP2 and PLAAT4 were up-regulated, while DLD exhibited downregulation in AD cerebral cortex tissue. This was validated in two separate external datasets (GSE132903 and GSE33000). The AD group exhibited significantly altered immune cell composition compared to controls. In addition, GSEA identified various pathways commonly associated with three key DELMRGs. Moreover, the regulatory network of miRNA-TF for key DELMRGs was established. Finally, significant differences in immune cell levels and several pathways were identified between the two subclusters.

Conclusion
This study identified DLD, PLPP2, and PLAAT4 as key DELMRGs in AD progression, providing novel insights for AD prevention/treatment.
Insight into the underlying molecular mechanism of dilated cardiomyopathy through integrative analysis of data mining, iTRAQ-PRM proteomics and bioinformatics
Authors: Xiong Hongli , Zheng Zhe , Zhao Congcong , Zhao Minzhu , Wang Qi , Zhang Peng , Li Yongguo , Zhu Ying , Zhu Shisheng , Li Jianbo 
Published: September 2023

Abstract
Background
DCM is a common cardiomyopathy worldwide, which is characterized by ventricular dilatation and systolic dysfunction. DCM is one of the most widespread diseases contributing to sudden death and heart failure. However, our understanding of its molecular mechanisms is limited because of its etiology and underlying mechanisms. Hence, this study explored the underlying molecular mechanism of dilated cardiomyopathy through integrative analysis of data mining, iTRAQ-PRM proteomics and bioinformatics

Methods
DCM target genes were downloaded from the public databases. Next, DCM was induced in 20 rats by 8 weeks doxorubicin treatment (2.5 mg/kg/week). We applied isobaric tags for a relative and absolute quantification (iTRAQ) coupled with proteomics approach to identify differentially expressed proteins (DEPs) in myocardial tissue. After association analysis of the DEPs and the key target genes, subsequent analyses, including functional annotation, pathway enrichment, validation, were performed.

Results
Nine hundred thirty-five genes were identified as key target genes from public databases. Meanwhile, a total of 782 DEPs, including 348 up-regulated and 434 down-regulated proteins, were identified in our animal experiment. The functional annotation of these DEPs revealed complicated molecular mechanisms including TCA cycle, Oxidative phosphorylation, Cardiac muscle contraction. Moreover, the DEPs were analyzed for association with the key target genes screened in the public dataset. We further determined the importance of these three pathways.

Conclusion
Our results demonstrate that TCA cycle, Oxidative phosphorylation, Cardiac muscle contraction played important roles in the detailed molecular mechanisms of DCM.
Analysis of differential membrane proteins related to matrix stiffness-mediated metformin resistance in hepatocellular carcinoma cells
Authors: Gao Xiangyu , Qian Jiali , Zhang Yang , Wang Heming , Cui Jiefeng , Yang Yehong 
Published: September 2023

Abstract
Background
Our previous work shows that increased matrix stiffness not only alters malignant characteristics of hepatocellular carcinoma (HCC) cells, but also attenuates metformin efficacy in treating HCC cells. Here, we identified differential membrane proteins related to matrix stiffness-mediated metformin resistance for better understand therapeutic resistance of metformin in HCC.

Methods
Differential membrane proteins in HCC cells grown on different stiffness substrates before and after metformin intervention were screened and identified using isobaric tags for relative and absolute quantification (iTRAQ) labeling coupled with the liquid chromatography-tandem mass spectrometry (LC–MS/MS), then bioinformatic analysis were applied to determine candidate membrane protein and their possible signaling pathway.

Results
A total of 5159 proteins were identified and 354 differential membrane proteins and membrane associated proteins, which might be associated with matrix stiffness-mediated metformin resistance were discovered. Then 94 candidate membrane proteins including 21 up-regulated protein molecules and 73 down-regulated protein molecules were further obtained. Some of them such as Annexin A2 (ANXA2), Filamin-A (FLNA), Moesin (MSN), Myosin-9 (MYH9), Elongation factor 2 (eEF2), and Tax1 binding Protein 3 (TAX1BP3) were selected for further validation. Their expressions were all downregulated in HCC cells grown on different stiffness substrates after metformin intervention. More importantly, the degree of decrease was obviously weakened on the higher stiffness substrate compared with that on the lower stiffness substrate, indicating that these candidate membrane proteins might contribute to matrix stiffness-mediated metformin resistance in HCC.

Conclusions
There was an obvious change in membrane proteins in matrix stiffness-mediated metformin resistance in HCC cells. Six candidate membrane proteins may reflect the response of HCC cells under high stiffness stimulation to metformin intervention, which deserve to be investigated in the future.
Lymph node ratio and hematological parameters predict relapse-free survival in patients with high grade rectal neuroendocrine neoplasms after radical resection: a multicenter prognostic study
Authors: Zeng Xinyu , Zhang Peng , Zhu Guangsheng , Li Chengguo , Zhang Rui , Yu Minhao , Lin Guole , Di Maojun , Jiang Congqing , Li Yong , Sun Yueming , Xia Lijian , Chi Pan , Tao Kaixiong 
Published: September 2023

Abstract
Background
The prognostic nutritional index (PNI), alkaline phosphatase (ALP), and lymph node ratio (LNR) are reportedly related to prognosis. The aim of this study was to elucidate the clinical importance of the LNR and hematological parameters in patients with high grade rectal neuroendocrine neoplasms (HG-RNENs) who were undergoing radical resection.

Methods
We reviewed the medical records of patients with HG-RNENs from 17 large-scale medical centers in China (January 1, 2010–April 30, 2022). A nomogram was constructed by using a proportional hazard model. Bootstrap method was used to draw calibration plots to validate the reproducibility of the model. Concordance index (C-Index), decision curve analysis (DCA), and time-dependent area under the receiver operating characteristic curve (TD-AUC) analysis were used to compare the prognostic predictive power of the new model with American Joint Committee on Cancer (AJCC) TNM staging and European Neuroendocrine Tumor Society (ENETS) TNM staging.

Results
A total of 85 patients with HG-RNENs were enrolled in this study. In the 45 patients with HG-RNENs who underwent radical resection, PNI ≤ 49.13 (HR: 3.997, 95% CI: 1.379–11.581, P = 0.011), ALP > 100.0 U/L (HR: 3.051, 95% CI: 1.011–9.205, P = 0.048), and LNR > 0.40 (HR: 6.639, 95% CI: 2.224–19.817, P = 0.0007) were independent predictors of relapse-free survival. The calibration plots suggested that the nomogram constructed based on the three aforementioned factors had good reproducibility. The novel nomogram revealed a C-index superior to AJCC TNM staging (0.782 vs 0.712) and ENETS TNM staging (0.782 vs 0.657). Also, the new model performed better compared to AJCC TNM staging and ENETS TNM staging in DCA and TD-AUC analyses.

Conclusions
LNR, ALP, and PNI were independent prognostic factors in patients with HG-RNENs after radical resection, and the combined indicator had better predictive efficacy compared with AJCC TNM staging and ENETS TNM staging.
Reciprocal regulation of TWIST1 and OGT determines the decitabine efficacy in MDS/AML
Authors: Li Hongjiao , Wang Yi , Feng Shuang , Chang Kaijing , Yu Xinwen , Yang Fenfang , Huang Haozhe , Wang Yuanbo , Li Xiang , Guan Feng 
Published: September 2023

AbstractChemoresistance poses a significant impediment to effective treatment strategies for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Our previous study unveiled that oncogene TWIST1 interacted with DNA methyltransferase 3a (DNMT3a) to regulate the decitabine (DAC) resistance in MDS/AML. However, the underlying mechanism of TWIST1 dysregulation in DAC resistance remained enigmatic. Here, we found that O-GlcNAc modification was upregulated in CD34+ cells from MDS/AML patients who do not respond to DAC treatment. Functional study revealed that O-GlcNAcylation could stabilize TWIST1 by impeding its interaction with ubiquitin E3 ligase CBLC. In addition, as one typical transcription factor, TWIST1 could bind to the promoter of O-GlcNAc transferase (OGT) gene and activate its transcription. Collectively, we highlighted the crucial role of the O-GlcNAcylated TWIST1 in the chemoresistance capacity of MDS/AML clonal cells, which may pave the way for the development of a new therapeutic strategy targeting O-GlcNAcylated proteins and reducing the ratio of MDS/AML relapse.
Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis
Authors: Ren Jun-Song , Bai Wen , Ding Jing-Juan , Ge Hui-Min , Wang Su-Yu , Chen Xi , Jiang Qin 
Published: September 2023

Abstract
Background
Pathological neovascularization plays a pivotal role in the onset and progression of tumors and neovascular eye diseases. Despite notable advancements in the development of anti-angiogenic medications that target vascular endothelial growth factor (VEGF) and its receptors (VEGFRs), the occurrence of adverse reactions and drug resistance has somewhat impeded the widespread application of these drugs. Therefore, additional investigations are warranted to explore alternative therapeutic targets. In recent years, owing to the swift advancement of high-throughput sequencing technology, pan-cancer analysis and single-cell sequencing analysis have emerged as pivotal methodologies and focal areas within the domain of omics research, which is of great significance for us to find potential targets related to the regulation of pathological neovascularization.

Methods
Pan-cancer analysis and scRNA-seq data analysis were employed to forecast the association between Actin filament-associated protein 1 like 1 (AFAP1L1) and the development of tumors and endothelial cells. Tumor xenograft model and ocular pathological neovascularization model were constructed as well as Isolectin B4 (IsoB4) staining and immunofluorescence staining were used to assess the effects of AFAP1L1 on the progression of neoplasms and neovascular eye diseases in vivo. Transwell assay, wound scratch assay, tube forming assay, three-dimensional germination assay, and rhodamine-phalloidin staining were used to evaluate the impact of AFAP1L1 on human umbilical vein endothelial cells (HUVECs) function in vitro; Dual luciferase reporting, qRT-PCR and western blot were used to investigate the upstream and downstream mechanisms of pathological neovascularization mediated by AFAP1L1.

Results
Our investigation revealed that AFAP1L1 plays a crucial role in promoting the development of various tumors and demonstrates a strong correlation with endothelial cells. Targeted suppression of AFAP1L1 specifically in endothelial cells in vivo proves effective in inhibiting tumor formation and ocular pathological neovascularization. Mechanistically, AFAP1L1 functions as a hypoxia-related regulatory protein that can be activated by HIF-1α. In vitro experiments demonstrated that reducing AFAP1L1 levels can reverse hypoxia-induced excessive angiogenic capacity in HUVECs. The principal mechanism of angiogenesis inhibition entails the regulation of tip cell behavior through the YAP-DLL4-NOTCH axis.

Conclusion
In conclusion, AFAP1L1, a newly identified hypoxia-related regulatory protein, can be activated by HIF-1α. Inhibiting AFAP1L1 results in the inhibition of angiogenesis by suppressing the germination of endothelial tip cells through the YAP-DLL4-NOTCH axis. This presents a promising therapeutic target to halt the progression of tumors and neovascular eye disease.