bluuebunny/crossref_metadata_2025_split huggingface dataset:
Higher risk of cardiovascular mortality than cancer mortality among long-term cancer survivors
Authors: Wang Zhipeng , Fan Zeyu , Yang Lei , Liu Lifang , Sheng Chao , Song Fengju , Huang Yubei , Chen Kexin 
Published: January 2023

BackgroundPrevious studies focused more on the short-term risk of cardiovascular (CV) death due to traumatic psychological stress after a cancer diagnosis and the acute cardiotoxicity of anticancer treatments than on the long-term risk of CV death.MethodsTime trends in the proportions of CV death (PCV), cancer death (PCA), and other causes in deaths from all causes were used to show preliminary relationships among the three causes of death in 4,806,064 patients with cancer from the Surveillance, Epidemiology, and End Results (SEER) program. Competing mortality risk curves were used to investigate when the cumulative CV mortality rate (CMRCV) began to outweigh the cumulative cancer mortality rate (CMRCA) for patients with cancer who survived for more than 10 years. Multivariable competing risk models were further used to investigate the potential factors associated with CV death.ResultsFor patients with cancer at all sites, the PCV increased from 22.8% in the 5th year after diagnosis to 31.0% in the 10th year and 35.7% in the 20th year, while the PCA decreased from 57.7% in the 5th year after diagnosis to 41.2 and 29.9% in the 10th year and 20th year, respectively. The PCV outweighed the PCA (34.6% vs. 34.1%) since the 15th year for patients with cancer at all sites, as early as the 9th year for patients with colorectal cancer (37.5% vs. 33.2%) and as late as the 22nd year for patients with breast cancer (33.5% vs. 30.6%). The CMRCV outweighed the CMRCA since the 25th year from diagnosis. Multivariate competing risk models showed that an increased risk of CV death was independently associated with older age at diagnosis [hazard ratio and 95% confidence intervals [HR (95%CI)] of 43.39 (21.33, 88.28) for ≥ 80 vs. ≤ 30 years] and local metastasis [1.07 (1.04, 1.10)] and a decreased risk among women [0.82 (0.76, 0.88)], surgery [0.90 (0.87, 0.94)], and chemotherapy [0.85 (0.81, 0.90)] among patients with cancer who survived for more than 10 years. Further analyses of patients with cancer who survived for more than 20 years and sensitivity analyses by cancer at all sites showed similar results.ConclusionCV death gradually outweighs cancer death as survival time increases for most patients with cancer. Both the cardio-oncologist and cardio-oncology care should be involved to reduce CV deaths in long-term cancer survivors.
Association between estimated pulse wave velocity and silent lacunar infarct in a Korean population
Authors: Zhou Yaping , Zhang Yu , Xu Gang , Shang Xiuli 
Published: January 2023

AimsPrevious studies have proposed the estimated pulse wave velocity (ePWV) as a simple and cost-effective measure of arterial stiffness. Since arterial stiffness plays a role in the progression of silent lacunar infarct (SLI), our present work aims to evaluate the association between ePWV and the presence of SLI.MethodsThe present work was based on a cross-section study. Our study included 1,011 neurologically healthy Korean participants. The SLI was evaluated using brain magnetic resonance images (MRI). The ePWV was derived from a published equation using age and mean blood pressure (MBP). Logistic regression analyses were performed to investigate the association between ePWV and SLI. The linear relationship and robustness were evaluated using smooth curve fitting and subgroup analyses, respectively.ResultsThe prevalence of SLI was 11.87%. After fully adjusting for covariates, per 1 m/s increase of ePWV casted 31% additional risk for SLI (P = 0.009). When dividing the ePWV into quartiles, the top quartile had 4.01 times risk compared with the bottom quartile. The increasing trend across the quartiles was statistically significant (P for trend &lt; 0.001). Consistently, smooth curve fitting revealed that the risk of SLI elevated linearly with the increase of ePWV. Finally, subgroup analysis suggested that the association was robust in several sub-populations divided by age, sex, smoking, hypertension, diabetes mellitus (DM), coronary artery occlusive disease (CAOD), hyperlipidemia, and statin medication (all P for interaction &gt; 0.05).ConclusionThe current study revealed an independent and positive association between ePWV and the presence of SLI in a neurologically healthy Korean population.
Assessment of fractional flow reserve in intermediate coronary stenosis using optical coherence tomography-based machine learning
Authors: Cha Jung-Joon , Nguyen Ngoc-Luu , Tran Cong , Shin Won-Yong , Lee Seul-Gee , Lee Yong-Joon , Lee Seung-Jun , Hong Sung-Jin , Ahn Chul-Min , Kim Byeong-Keuk , Ko Young-Guk , Choi Donghoon , Hong Myeong-Ki , Jang Yangsoo , Ha Jinyong , Kim Jung-Sun 
Published: January 2023

ObjectivesThis study aimed to evaluate and compare the diagnostic accuracy of machine learning (ML)- fractional flow reserve (FFR) based on optical coherence tomography (OCT) with wire-based FFR irrespective of the coronary territory.BackgroundML techniques for assessing hemodynamics features including FFR in coronary artery disease have been developed based on various imaging modalities. However, there is no study using OCT-based ML models for all coronary artery territories.MethodsOCT and FFR data were obtained for 356 individual coronary lesions in 130 patients. The training and testing groups were divided in a ratio of 4:1. The ML-FFR was derived for the testing group and compared with the wire-based FFR in terms of the diagnosis of ischemia (FFR ≤ 0.80).ResultsThe mean age of the subjects was 62.6 years. The numbers of the left anterior descending, left circumflex, and right coronary arteries were 130 (36.5%), 110 (30.9%), and 116 (32.6%), respectively. Using seven major features, the ML-FFR showed strong correlation (r = 0.8782, P &lt; 0.001) with the wire-based FFR. The ML-FFR predicted wire-based FFR ≤ 0.80 in the test set with sensitivity of 98.3%, specificity of 61.5%, and overall accuracy of 91.7% (area under the curve: 0.948). External validation showed good correlation (r = 0.7884, P &lt; 0.001) and accuracy of 83.2% (area under the curve: 0.912).ConclusionOCT-based ML-FFR showed good diagnostic performance in predicting FFR irrespective of the coronary territory. Because the study was a small-size study, the results should be warranted the performance in further large-scale research.
Evaluation and Selection of the Inhaler Device for Treprostinil Palmitil Inhalation Powder
Authors: Gauani Helena , Baker Thomas , Li Zhili , Malinin Vladimir S. , Perkins Walter , Sullivan Eugene , Cipolla David 
Published: January 2023

Treprostinil palmitil (TP) is a prodrug of treprostinil that has been formulated as an inhaled powder, termed TPIP, for evaluation in patients with pulmonary arterial hypertension. In these characterization studies we investigated the aerosol performance of TPIP in response to changes in capsule fill, device resistance, and inspiratory flow rate to enable selection of an inhaler for clinical use. Capsules containing 8, 16 or 32 mg of TPIP (80, 160, or 320 μg TP, respectively) were evaluated using four commercially-available, breath-actuated RS01 devices (Plastiape, S. p.A., Osnago, Italy) with low, medium, high or ultra-high inspiratory resistances, creating 12 different capsule and device configurations for evaluation. Aerosol characterization was performed using the next generation impactor at compendial conditions of 23°C and 35% relative humidity and a flow rate corresponding to a 4 kPa pressure drop. The aerosol mass median aerodynamic diameter, geometric standard deviation, fine particle fraction, emitted dose and fine particle dose (FPD) were calculated from the in vitro impactor data. The TP emitted dose at 4 kPa exceeded 75% for all 12 capsule and device configurations. The FPD, an estimate of the respirable dose, varied between 61.0 and 70.6% of the loaded TP dose for all four devices with the 8 and 16 mg TPIP capsule dose. For the 32 mg TPIP capsule dose, the FPD remained above 61.0% for the high and ultra-high resistance devices but decreased to 48.5 and 52.6% for the low and medium resistance devices, respectively. Based on this initial data, the high resistance device was selected for additional characterization studies at 40 and 80 L/min corresponding to pressure drops of 1.4 and 5.4 kPa. The FPD was relatively insensitive to changes in flow rate, providing an expectation of a consistent total lung dose of TP under scenarios simulating variability in how the device is used. Based on these findings, the high resistance device was chosen for further development in human clinical trials.
The role of earthquakes and storms in the fluvial export of terrestrial organic carbon along the eastern margin of the Tibetan plateau: A biomarker perspective
Authors: Wang Jin , Ma Tian , Zhang Fei , Hilton Robert G. , Feng Xiaojuan , Jin Zhangdong 
Published: January 2023

Driven by earthquakes and intense rainfall, steep tectonically active mountains are hotspots of terrestrial organic carbon mobilization from soils, rocks, and vegetation by landslides into rivers. Subsequent delivery and fluvial mobilization of organic carbon from different sources can impact atmospheric CO2 concentrations across a range of timescales. Extreme landslide triggering events can provide insight on processes and rates of carbon export. Here we used suspended sediment collected from 2005 to 2012 at the upper Min Jiang, a main tributary of the Yangtze River on the eastern margin of the Tibetan Plateau, to compare the erosion of terrestrial organic carbon before and after the 2008 Wenchuan earthquake and a storm-derived debris flow event in 2005. To constrain the source of riverine particulate organic carbon (POC), we quantified lignin phenols and n-alkanoic acids in the suspended sediments, catchment soils and landslide deposits. We found that riverine POC had higher inputs of less-degraded, discrete organic matter at high suspended sediment loads, while the source of POC seemed stochastic at low suspended sediment concentrations. The debris flow in 2005 mobilized a large amount of POC, resulting in an export of lignin within a single day equivalent to a normal year. In comparison, the 2008 Wenchuan earthquake increased the flux of POC and particulate lignin, albeit with limited impact on POC sources in comparison to seasonal variations. Our results highlight the important role of episodic events in the fluvial export of terrestrial carbon.
Multi-omics analysis of N6-methyladenosine reader IGF2BP3 as a promising biomarker in pan-cancer
Authors: Chen Pin , Xu Jing , Cui Zihan , Wu Silin , Xie Tao , Zhang Xiaobiao 
Published: January 2023

BackgroundInsulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) has been reported to exhibit an oncogenic effect as an RNA-binding protein (RBP) by promoting tumor cell proliferation, migration and invasion in several tumor types. However, a pan-cancer analysis of IGF2BP3 is not currently available, and the exact roles of IGF2BP3 in prognosis and immunology in cancer patients remain enigmatic. The main aim of this study was to provide visualization of the systemic prognostic landscape of IGF2BP3 in pan-cancer and to uncover the potential relationship between IGF2BP3 expression in the tumor microenvironment and immune infiltration profile.MethodsRaw data on IGF2BP3 expression were obtained from GTEx, CCLE, TCGA, and HPA data portals. We have investigated the expression patterns, diagnostic and prognostic significance, mutation landscapes, functional analysis, and functional states of IGF2BP3 utilizing multiple databases, including HPA, TISIDB, cBioPortal, GeneMANIA, GESA, and CancerSEA. Moreover, the relationship of IGF2BP3 expression with immune infiltrates, TMB, MSI and immune-related genes was evaluated in pan-cancer. IGF2BP3 with drug sensitivity analysis was performed from the CellMiner database. Furthermore, the expression of IGF2BP3 in different grades of glioma was detected by immunohistochemical staining and western blot.ResultsWe found that IGF2BP3 was ubiquitously highly expressed in pan-cancer and significantly correlated with diagnosis, prognosis, TMB, MSI, and drug sensitivity in various types of cancer. Besides, IGF2BP3 was involved in many cancer pathways and varied in different immune and molecular subtypes of cancers. Additionally, IGF2BP3 is critically associated with genetic markers of immunomodulators in various cancers. Finally, we validated that IGF2BP3 protein expression was significantly higher in glioma than in normal tissue, especially in GBM.ConclusionsIGF2BP3 may be a potential molecular biomarker for diagnosis and prognosis in pan-cancer, especially for glioma. It could become a novel therapeutic target for various cancers.
Construction and systematic evaluation of a machine learning-based cuproptosis-related lncRNA score signature to predict the response to immunotherapy in hepatocellular carcinoma
Authors: Lu Dingyu , Liao Jian , Cheng Hao , Ma Qian , Wu Fei , Xie Fei , He Yingying 
Published: January 2023

IntroductionHepatocellular carcinoma (HCC) is a common malignant cancer with a poor prognosis. Cuproptosis and associated lncRNAs are connected with cancer progression. However, the information on the prognostic value of cuproptosis-related lncRNAs is still limited in HCC.MethodsWe isolated the transcriptome and clinical information of HCC from TCGA and ICGC databases. Ten cuproptosis-related genes were obtained and related lncRNAs were correlated by Pearson’s correlation. By performing lasso regression, we created a cuproptosis-related lncRNA prognostic model based on the cuproptosis-related lncRNA score (CLS). Comprehensive analyses were performed, including the fields of function, immunity, mutation and clinical application, by various R packages.ResultsTen cuproptosis-related genes were selected, and 13 correlated prognostic lncRNAs were collected for model construction. CLS was positively or negatively correlated with cancer-related pathways. In addition, cell cycle and immune related pathways were enriched. By performing tumor microenvironment (TME) analysis, we determined that T-cells were activated. High CLS had more tumor characteristics and may lead to higher invasiveness and treatment resistance. Three genes (TP53, CSMD1 and RB1) were found in high CLS samples with more mutational frequency. More amplification and deletion were detected in high CLS samples. In clinical application, a CLS-based nomogram was constructed. 5-Fluorouracil, gemcitabine and doxorubicin had better sensitivity in patients with high CLS. However, patients with low CLS had better immunotherapeutic sensitivity.ConclusionWe created a prognostic CLS signature by machine learning, and we comprehensively analyzed the signature in the fields of function, immunity, mutation and clinical application.
Senescent renal tubular epithelial cells activate fibroblasts by secreting Shh to promote the progression of diabetic kidney disease
Authors: Wang Dan , Yin Ling , Chen Rongyu , Tan Wanlin , Liang Luqun , Xiang Jiayi , Zhang Huifang , Zhou Xingcheng , Deng Huaqing , Guo Bing , Wang Yuanyuan 
Published: January 2023

IntroductionDiabetic kidney disease (DKD) is one of the complications of diabetes; however, the pathogenesis is not yet clear. A recent study has shown that senescence is associated with the course of DKD. In the present study, we explored whether senescent renal tubular cells promote renal tubulointerstitial fibrosis by secreting Sonic hedgehog (Shh) which mediates fibroblast activation and proliferation in DKD.MethodsA 36-week-old db/db mice model and the renal tubular epithelial cells were cultured in high glucose (HG, 60 mmol/L) medium for in vivo and in vitro experiments.ResultsCompared to db/m mice, blood glucose, microalbuminuria, serum creatinine, urea nitrogen, and UACR (microalbuminuria/urine creatinine) were markedly increased in db/db mice. Collagen III, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-alpha (TNF-α) were also increased in db/db mice kidneys, suggesting fibrosis and inflammation in the organ. Moreover, the detection of SA-β-galactosidase (SA-β-Gal) showed that the activity of SA-β-Gal in the cytoplasm of renal tubular epithelial cells increased, and the cell cycle inhibition of the expression of senescence-related gene cell cycle inhibitor p16INK4A protein and p21 protein increased, indicating that renal fibrosis in db/db mice was accompanied by cell senescence. Furthermore, Shh is highly expressed in the injured renal tubules and in the kidney tissue of db/db mice, as detected by enzyme-linked immunosorbent assay (ELISA). The results of immunofluorescence staining showed increased positive staining for Shh in renal tubular epithelial cells of db/db mice and decreased positive staining for Lamin B1, but increased positive staining for γH2A.X in cells with high Shh expression; similar results were obtained in vitro. In addition, HG stimulated renal tubular epithelial cells to secrete Shh in the supernatant of the medium. D-gal treatment of renal tubular epithelial cells increased the protein levels of Shh and p21. We also found enhanced activation and proliferation of fibroblasts cultured with the supernatant of renal tubular epithelial cells stimulated by HG medium but the proliferative effect was significantly diminished when co-cultured with cyclopamine (CPN), an inhibitor of the Shh pathway.DiscussionIn conclusion, HG induces renal tubular epithelial cell senescence, and the secretion of senescence-associated proteins and Shh mediates inflammatory responses and fibroblast activation and proliferation, ultimately leading to renal fibrosis.
Infection-specific PET imaging with 18F-fluorodeoxysorbitol and 2-[18F]F-ρ-aminobenzoic acid: An extended diagnostic tool for bacterial and fungal diseases
Authors: Rua Marta , Simón Jon Ander , Collantes María , Ecay Margarita , Leiva José , Carmona-Torre Francisco , Ramos Rocío , Pareja Félix , Pulagam Krishna R. , Llop Jordi , Del Pozo José Luis , Peñuelas Iván 
Published: January 2023

IntroductionSuspected infectious diseases located in difficult-to-access sites can be challenging due to the need for invasive procedures to isolate the etiological agent. Positron emission tomography (PET) is a non-invasive imaging technology that can help locate the infection site. The most widely used radiotracer for PET imaging (2-deoxy-2[18F] fluoro-D-glucose: [18F]FDG) shows uptake in both infected and sterile inflammation. Therefore, there is a need to develop new radiotracers able to specifically detect microorganisms.MethodsWe tested two specific radiotracers: 2-deoxy-2-[18F]-fluoro-D-sorbitol ([18F]FDS) and 2-[18F]F-ρ-aminobenzoic acid ([18F]FPABA), and also developed a simplified alternative of the latter for automated synthesis. Clinical and reference isolates of bacterial and yeast species (19 different strains in all) were tested in vitro and in an experimental mouse model of myositis infection.Results and discussionNon-lactose fermenters (Pseudomonas aeruginosa and Stenotrophomonas maltophilia) were unable to take up [18F]FDG in vitro. [18F]FDS PET was able to visualize Enterobacterales myositis infection (i.e., Escherichia coli) and to differentiate between yeasts with differential assimilation of sorbitol (i.e., Candida albicans vs. Candida glabrata). All bacteria and yeasts tested were detected in vitro by [18F]FPABA. Furthermore, [18F]FPABA was able to distinguish between inflammation and infection in the myositis mouse model (E. coli and Staphylococcus aureus) and could be used as a probe for a wide variety of bacterial and fungal species.
PIN1 and PIN4 inhibition via parvulin impeders Juglone, PiB, ATRA, 6,7,4′-THIF, KPT6566, and EGCG thwarted hepatitis B virus replication
Authors: Saeed Umar , Piracha Zahra Zahid 
Published: January 2023

IntroductionHuman parvulin peptidyl prolyl cis/trans isomerases PIN1 and PIN4 play important roles in cell cycle progression, DNA binding, protein folding and chromatin remodeling, ribosome biogenesis, and tubulin polymerization. In this article, we found that endogenous PIN1 and PIN4 were upregulated in selected hepatocellular carcinoma (HCC) cell lines.MethodsIn this study, we inhibited PIN1 and PIN4 via parvulin inhibitors (Juglone, PiB, ATRA, 6,7,4′-THIF, KPT6566, and EGCG). The native agarose gel electrophoresis (NAGE) immunoblotting analysis revealed that upon PIN1 and/ or PIN4 inhibition, the HBc protein expression and core particle or capsid synthesis reduced remarkably. The effects of PIN4 inhibition on hepatitis B virus (HBV) replication were more pronounced as compared to that of PIN1. The Northern and Southern blotting revealed reduced HBV RNA and DNA levels.ResultsDuring the HBV course of infection, Juglone, PiB, ATRA, 6,7,4′-THIF, KPT6566, and EGCG-mediated inhibition of PIN1 and PIN4 significantly lowered HBV transcriptional activities without affecting total levels of covalently closed circular DNA (cccDNA). Similar to the inhibitory effects of PIN1 and PIN4 on HBV replication, the knockdown of PIN1 and PIN4 in HBV infection cells revealed significantly reduced amounts of intracellular HBc, HBs, HBV pgRNA, SmRNAs, core particles, and HBV DNA synthesis. Similarly, PIN1 and PIN4 KD abrogated extracellular virion release, naked capsid levels, and HBV DNA levels. In comparison with PIN1 KD, the PIN4 KD showed reduced HBc and/or core particle stabilities, indicating that PIN4 is more critically involved in HBV replication. Chromatin immunoprecipitation (ChIP) assays revealed that in contrast to DNA binding PIN4 proteins, the PIN1 did not show binding to cccDNA. Similarly, upon PIN1 KD, the HBc recruitment to cccDNA remained unaffected. However, PIN4 KD significantly abrogated PIN4 binding to cccDNA, followed by HBc recruitment to cccDNA and restricted HBV transcriptional activities. These effects were more pronounced in PIN4 KD cells upon drug treatment in HBV-infected cells.ConclusionThe comparative analysis revealed that in contrast to PIN1, PIN4 is more critically involved in enhancing HBV replication. Thus, PIN1 and PIN4 inhibition or knockdown might be novel therapeutic targets to suppress HBV infection. targets to suppress HBV infection.