bluuebunny/crossref_metadata_2025_split huggingface dataset:
The regulatory role of exosomes in venous thromboembolism
Authors: Ye Sheng-Lin , Li Wen-Dong , Li Wei-Xiao , Xiao Lun , Ran Feng , Chen Meng-Meng , Li Xiao-Qiang , Sun Li-Li 
Published: August 2022

Exosomes are nanoscale endocytic vesicles, 30–150 nm in diameter, secreted by most cells. They mainly originate from multivesicular bodies formed by intracellular invagination of lysosomal microparticles, and released into the extracellular matrix after fusion of multivesicular bodies with cell membrane. Studies have shown that exosomes contain a variety of active molecules, such as proteins, lipids and RNAs (such as mRNA, miRNA, lncRNA, circRNA, etc.), which regulate the behavior of recipient cells and serve as circulating biomarkers of diseases, including thrombosis. Therefore, exosome research is important for the diagnosis, treatment, therapeutic monitoring, and prognosis of thrombosis in that it can reveal the counts, surface marker expression, protein, and miRNA cargo involved. Recent studies have shown that exosomes can be used as therapeutic vectors for tissue regeneration and as alternative vectors for drug delivery. In this review, we summarize the physiological and biochemical characteristics, isolation, and identification of exosomes. Moreover, we focus on the role of exosomes in thrombosis, specifically venous thromboembolism, and their potential clinical applications, including as biomarkers and therapeutic vectors for thrombosis.
A new antioxidant made from a pterostilbene functionalized graphene nanocomposite as an efficient treatment for dry eye disease
Authors: Lin Mimi , Sun Xueqin , Ye Sihao , Chen Youyi , Gao Jing , Yuan Feng , Lin Na , Lawson Tom , Liu Yong , Deng Ruzhi 
Published: August 2022

Dry eye disease is a common condition that affects the eyes. It is caused by problems with the tear film and the tear dynamics. Dry eye can be caused by an increase in the amount of reactive oxygen species (ROS) in the corneal epithelium. The treatment for dry eye typically focuses on relieving the uncomfortable symptoms by using eye drops such as artificial tears, antibiotics, and by using anti-inflammatory/immunosuppressive agents such as cyclosporine, and lifitegrast. However, the recovery of patients with dry eye can take several years particularly if the symptoms are severe. This is because the present treatment approaches for dry eye are not based on its cause, e.g., the oxidative stress arising from the rapid increase in ROS. This work describes a new type of antioxidant made from pterostilbene (PS) and carboxyl-chitosan modified graphene (CG). The use of a hydrophilic two-dimensional CG nanosheet to improve the properties of PS is reported. Superior enhanced properties including better cellular permeability, long sustained release period (over 30 h), and antioxidant properties, were realized by using PS-CG. A hyperosmotic (HS) damaged human corneal epithelial cell (HCEC) model was used for antioxidant tests. This model has an intracellular ROS level 4 times more than that of a control group. The ROS content was declined efficiently to the same amount as normal cells in the PS-CG treated HS group. There was a significant decline in the content of lactate dehydrogenase (LDH) and the apoptosis rate of HCEC in the PS-CG treated HS group when compared to that seen in the HS model. Real-time polymerase chain reaction (PCR) and western blots (WB) were used to understand the antioxidant mechanism of PS-CG. The results showed that the antioxidant was working by activating the Keap1-Nrf2-ARE signalling pathway. In vivo testing testing using a dry eye mouse model suggested that the PS-CG acted as an efficient antioxidant. More tear production and healthier corneal and conjunctival epithelial cells were achieved when PC-CG was applied to this model. The use of PS-CG could be a new strategy for treating dry eye and other ocular diseases caused by ROS.
An artificial intelligence-based noninvasive solution to estimate pulmonary artery pressure
Authors: Zheng Jianwei , Abudayyeh Islam , Mladenov Georgi , Struppa Daniele , Fu Guohua , Chu Huimin , Rakovski Cyril 
Published: August 2022

AimsDesign to develop an artificial intelligence (AI) algorithm to accurately predict the pulmonary artery pressure (PAP) waveform using non-invasive signal inputs.Methods and resultsWe randomly sampled training, validation, and testing datasets from a waveform database containing 180 patients with pulmonary atrial catheters (PACs) placed for PAP waves collection. The waveform database consisted of six hemodynamic parameters from bedside monitoring machines, including PAP, artery blood pressure (ABP), central venous pressure (CVP), respiration waveform (RESP), photoplethysmogram (PPG), and electrocardiogram (ECG). We trained a Residual Convolutional Network using a training dataset containing 144 (80%) patients, tuned learning parameters using a validation set including 18 (10%) patients, and tested the performance of the method using 18 (10%) patients, respectively. After comparing all multi-stage algorithms on the testing cohort, the combination of the residual neural network model and wavelet scattering transform data preprocessing method attained the highest coefficient of determination R2 of 90.78% as well as the following other performance metrics and corresponding 95% confidence intervals (CIs): mean square error of 11.55 (10.22–13.5), mean absolute error of 2.42 (2.06–2.85), mean absolute percentage error of 0.91 (0.76–1.13), and explained variance score of 90.87 (85.32–93.31).ConclusionThe proposed analytical approach that combines data preprocessing, sampling method, and AI algorithm can precisely predict PAP waveform using three input signals obtained by noninvasive approaches.
Ammonia-oxidizing archaea and ammonia-oxidizing bacteria communities respond differently in oxy-gen-limited habitats
Authors: Du Jialin , Meng Lin , Qiu Mingsheng , Chen Shuaiwei , Zhang Binghui , Song Wenjing , Cong Ping , Zheng Xuebo 
Published: August 2022

Ammonia-oxidizing archaea (AOA) and bacteria (AOB) are the most important ammonia oxidation functional community, while the coastal environment just provides a different oxygen environment for the ammonia oxidation process. However, few surveys concentrated on the influence of oxygen concentration on the niche specialization of AOA and AOB in the ocean intertidal zones. Here, high-throughput sequencing by Illumina MiSeq and qPCR were applied to detect the change of abundance, diversity as well as community structure of both AOA and AOB with 0–60 cm sediments depth in the intertidal zone in Qingdao, China. Results showed that the AOA/AOB amoA gene copy numbers and AOA/AOB OTU numbers rate increased as sediment depth went more profound, which indicated that AOA was more adaptive to oxygen-limited niches compared to AOB. Oxygen indeed led to the niche specialization of AOA and AOB in intertidal sediments. The dominant AOA and AOB were the clusters of Nitrosopumilus and Nitrosospira, respectively, which indicated ecological success in the intertidal zone. A significant and positive correlation (p &lt; 0.01) between AOB abundance/AOB OTU numbers and Oxidation-reduction potential (ORP) was observed. In addition, both total nitrogen (TN) (p &lt; 0.01) and pH (p &lt; 0.05) were significantly negatively correlated to AOB abundance. TN was also significantly negatively correlated to AOB OTU numbers (p &lt; 0.05). Hence, oxygen led to niche specialization of AOA and AOB, especially under anoxic conditions, AOA played a dominant role in the process of ammonia oxidation. The Nitrosopumilus and Nitrosospira clusters were the dominant AOA and AOB, respectively, representing an ecological success in the intertidal zone.
A mendelian randomization study with populations of European ancestry rules out a causal relationship between inflammatory bowel disease and colorectal cancer
Authors: Li Fan , Liu Yuyuan , Wang Zhaodi , Zhao Qi , Li Yuqin , Tang Tongyu 
Published: August 2022

Background: Ulcerative colitis (UC), a subtype of inflammatory bowel disease (IBD), has been found to be associated with colorectal cancer (CRC) in observational studies, but there is no evidence to support a causal relationship or reverse causality between the two diseases.Methods: We employed two-sample bidirectional Mendelian randomization to estimate an unconfounded bidirectional causal relationship between IBD (including UC and Crohn’s disease (CD)) and colorectal cancer. After searching IEU GWAS database and filtering SNPs, we applied a variety of MR methods including IVW method using qualified instrumental variables, and conducted sensitivity analysis to detect the heterogeneity and pleiotropy of instrumental variables.Results: After using three groups of SNPs (CD: 106, UC: 113, IBD: 70), the IVW method MR analysis showed that the results were not significant (result for UC: odds ratio (OR) [95% Confidence Interval (CI)]: 0.9998 [0.9991–1.0005], p value: 0.58; result for CD: OR [95%CI]: 0.99962 [0.99912–1.00012], p value: 0.14; results for IBD: OR [95%CI]: 0.99959 [0.99869–1.00048], p value: 0.36). MR-Egger regression, WM method and MR-RAPS method reached the same conclusion. Sensitivity analysis did not reveal heterogeneity and pleiotropy. Bidirectional MR analysis was performed using the same procedure, and the results of IVW MR analysis were also not significant (result for CD: OR [95%CI]: 1.07985 [0.00049–2372.38304], p value 0.98; result for UC: OR [95%CI]: 0.27117 [0.00014–528.3707], p value: 0.74; result for IBD: OR [95%CI]: 0.47101 [0.0001–2242.94159], p value: 0.86). MR-Egger regression, WM method and MR-RAPS method also reached the same conclusion. Sensitivity analysis did not find any evidence of heterogeneity and pleiotropy.Conclusion: Contrary to the conclusions of previous observational studies, a two-sample MR analysis did not find a causal relationship or reverse causal relationship between IBD and CRC. Sporadic CRC (sCRC) may differ in pathogenesis from IBD-related CRC.
Association between frontal fibrosing Alopecia and Rosacea: Results from clinical observational studies and gene expression profiles
Authors: Liu Lin , Chen Yangmei , Chen Jiayi , Xue Yuzhou , Chen Tingqiao , Li Yuxin , Shao Xinyi , Chen Jin 
Published: August 2022

BackgroundIn recent years, frontal fibrosing alopecia (FFA), a type of scarring alopecia, has attracted increasing attention. Several studies have reported the frequent occurrence of rosacea in FFA; however, the association between FFA and rosacea and the underlying pathogenesis have not been thoroughly clarified. Thus, this study aimed to quantify these relationships and investigate their shared molecular mechanisms.MethodsWe evaluated the association between FFA and rosacea by analyzing clinical data from nine observational studies. We then analyzed the gene expression profiles of FFA and rosacea. First, differential expression analysis and weighted gene co-expression network analysis were used to identify the common differentially expressed genes (DEGs). Later, we conducted a functional enrichment analysis and protein-protein interaction network and used seven algorithms to identify hub genes. Then, we performed a correlation analysis between the hub genes and the gene set variation analysis scores of common pathways in the gene set enrichment analysis (GSEA). The results were validated using different datasets. Finally, transcription factors were predicted and verified, and CIBERSORT and single-sample GSEA were used to estimate the infiltrating immune cells.ResultsPatients with FFA had significantly higher odds for rosacea (pooled odds ratio [OR], 2.46; 95% confidence interval [CI], 1.78–3.40), and the pooled prevalence of rosacea in patients with FFA was 23% (95% CI, 14–23%). Furthermore, we identified 115 co-DEGs and 13 hub genes (CCR5, CCL19, CD2, CD38, CD83, CXCL8, CXCL9, CXCL10, CXCL11, CXCR4, IRF1, IRF8, and PTPRC). Seven pathways showed a high correlation with these hub genes. In addition, one TF, STAT1, was highly expressed in both diseases, and the results of the immune infiltration analysis indicated the importance of M1 macrophages and effector memory CD8+ T cells.ConclusionThis study contributes to the understanding of the relationship between FFA and rosacea, and based on the hub genes, we reveal the potential pathologies shared by the two diseases. This finding provides new insights of underlying molecular mechanisms and it may inspire future research on this comorbidity.
The association between cognitive impairment and 30-day mortality among older Chinese inpatients
Authors: Zhang Xiao-Ming , Jiao Jing , Guo Na , Zhu Chen , Li Zhen , Lv Dongmei , Wang Hui , Jin Jingfen , Wen Xianxiu , Zhao Shengxiu , Wu Xinjuan , Xu Tao 
Published: August 2022

PurposeAlthough the association between cognitive impairment and mortality has been widely described among community-dwelling older adults, this association in hospitalized patients was limited.ObjectivesThis study's purpose was to explore the association between cognitive impairment and 30-day mortality after adjustment of factors among Chinese in-patients.MethodsThis was a large-scale prospective study based on a cohort of patients aged 65 years and older, whose cognitive function was assessed using the Mini-Cog instrument, followed up at 30-days for mortality. Multivariate logistic regression models were used to assess the association between cognitive impairment and 30-day mortality.ResultsThere were 9,194 inpatients in our study, with an average age of 72.41 ± 5.72. The prevalence of cognitive impairment using the Mini-Cog instrument was 20.5%. Multivariable analyses showed that patients with cognitive impairment have an increased risk of 30-day mortality, compared to those with normal cognitive function (OR = 2.83,95%CI:1.89–4.24) in an unadjusted model. In the fully adjusted model, Patients with cognitive impairment had an increased risk of 30-day mortality compared to those with normal cognitive function in the completely adjusted model (OR = 1.76,95% CI: 1.14–2.73). Additionally, this association still existed and was robust after performing a stratified analysis of age, gender, frailty and depression, with no significant interaction (P &gt; 0.05).ConclusionsOur study found that older Chinese in-patients with cognitive impairment have a 1.76-fold risk of 30-day mortality compared to patients with normal cognitive function, suggesting that clinicians and nurses need to early implement cognitive function screening and corresponding interventions to improve clinical outcomes for older in-patients.
Risk prediction of dysthyroid optic neuropathy based on CT imaging features combined the bony orbit with the soft tissue structures
Authors: Cheng Shengnan , Ming Yangcan , Hu Mang , Zhang Yan , Jiang Fagang , Wang Xinghua , Xiao Zefeng 
Published: August 2022

PurposeTo analyze computed tomographic (CT) imaging features of patients with dysthyroid optic neuropathy (DON) retrospectively and deduce a more appropriate predictive model.MethodsThe CT scans and medical records of 60 patients with clinically proven Graves' ophthalmopathy (GO) with (26 women and 10 men) and without DON (16 women and 8 men) were retrospectively reviewed, and 20 age- and sex-matched control participants (12 women and 8 men) were enrolled consecutively. The bony orbit [orbital rim angle (ORA), medial and lateral orbital wall angles (MWA and LWA), orbital apex angle (OAA), and length of the lateral orbital wall (LWL)], and the soft tissue structures [maximum extraocular muscle diameters (Max EOMD), muscle diameter index (MDI), medial and lateral rectus bulk from inter-zygomatic line (MRIZL and LRIZL), proptosis, intraorbital optic nerve stretching length (IONSL), superior ophthalmic vein diameter (SOVD), apical crowding, and presence of intracranial fat prolapse] were assessed on a clinical workstation. The CT features among groups were compared, and a multivariate logistic regression analysis was performed to evaluate the predictive features of DON.ResultsAll bony orbital angle indicators, except ORA (p = 0.461), were statistically different among the three groups (all p &lt; 0.05). The values of MWA, LWA, OAA, and LWL were larger in the orbits with the DON group than in the orbits without the DON group (all p &lt; 0.05). The MDI, MRIZL, proptosis, IONSL, and SOVD were statistically significantly different among the three groups (all p &lt; 0.05), in which the orbits with the DON group were significantly higher than the orbits without the DON group and control group. The apical crowding was more severe in the orbits with the DON group than in the orbits without the DON group (p = 0.000). There were no significant differences in the LRIZL and the presence of intracranial fat prolapse (all p &gt; 0.05). The multivariate regression analysis showed that the MWA, MDI, and SOVD were the independent factors predictive of DON. The sensitivity and specificity for the presence of DON by combining these three indicators were 89 and 83%, respectively.ConclusionBone and soft tissue CT features are useful in the risk prediction of DON, especially the MWA, MDI, and SOVD were the independent factors predictive of DON.
Diaphragm dysfunction after severe COVID-19: An ultrasound study
Authors: Boussuges Alain , Habert Paul , Chaumet Guillaume , Rouibah Rawah , Delorme Lea , Menard Amelie , Million Matthieu , Bartoli Axel , Guedj Eric , Gouitaa Marion , Zieleskiewicz Laurent , Finance Julie , Coiffard Benjamin , Delliaux Stephane , Brégeon Fabienne 
Published: August 2022

BackgroundSARS-CoV-2 infection can impair diaphragm function at the acute phase but the frequency of diaphragm dysfunction after recovery from COVID-19 remains unknown.Materials and methodsThis study was carried out on patients reporting persistent respiratory symptoms 3–4 months after severe COVID-19 pneumonia. The included patients were selected from a medical consultation designed to screen for recovery after acute infection. Respiratory function was assessed by a pulmonary function test, and diaphragm function was studied by ultrasonography.ResultsIn total, 132 patients (85M, 47W) were recruited from the medical consultation. During the acute phase of the infection, the severity of the clinical status led to ICU admission for 58 patients (44%). Diaphragm dysfunction (DD) was detected by ultrasonography in 13 patients, two of whom suffered from hemidiaphragm paralysis. Patients with DD had more frequently muscle pain complaints and had a higher frequency of prior cardiothoracic or upper abdominal surgery than patients with normal diaphragm function. Pulmonary function testing revealed a significant decrease in lung volumes and DLCO and the dyspnea scores (mMRC and Borg10 scores) were significantly increased in patients with DD. Improvement in respiratory function was recorded in seven out of nine patients assessed 6 months after the first ultrasound examination.ConclusionAssessment of diaphragm function by ultrasonography after severe COVID-19 pneumonia revealed signs of dysfunction in 10% of our population. In some cases, ultrasound examination probably discovered an un-recognized pre-existing DD. COVID-19 nonetheless contributed to impairment of diaphragm function. Prolonged respiratory physiotherapy led to improvement in respiratory function in most patients.Clinical trial registration[www.cnil.fr], identifier [#PADS20-207].
Genomic insights from Paraclostridium bifermentans HD0315_2: General features and pathogenic potential
Authors: Zhao Hailan , Wang Jiaqi , Peng Yao , Cai Xunchao , Liu Yandi , Huang Wenqi , Huang Hongli , Nie Yuqiang 
Published: August 2022

BackgroundParaclostridium bifermentans is the most diverse distributed species of Paraclostridium and can cause fatal human infections under rare conditions. However, its pathogenic mechanisms and adaptation ability behind infections remain unclear. Herein, we reported the complete genome sequence of P. bifermentans HD0315_2 isolated from the feces of a patient with Crohn's disease. Then, we performed genomic analyses to understand its pathogenic mechanisms and adaptation ability.ResultsThe de novo assembly revealed that the HD0315_2 strain carried a circular chromosome of 3.27 Mb and six circular plasmids (19.41 to 139.50 kb). The phylogenomic analysis assigned the HD0315_2 strain as P. bifermentans and reclassified some previously non-P. bifermentans strains into this clade. The general genomic features showed that this species harbored a flexible genomic pool characterized by variable genome length and multiple plasmids. Then, the HD0315_2 strain was predicted as a human pathogen with high probability, and Listeria LIPI-1 virulence proteins were identified on its genome. Besides, abundant antibiotics/metal/stress resistant genes, such as asrABCH, cat, mccF, macB, entS, albA, bcrA, and tetB, were carried by either the genome or the plasmids. Furthermore, we proposed that transposase-directed horizontal gene transfer was responsible for the distribution of multiple copies of the hin gene in the plasmids.ConclusionThe flexible genomic pool of P. bifermentans encodes abundant functions for antimicrobial or oxidative stress resistance, helping it successfully inhabit and adapt to diverse environments. Moreover, P. bifermentans HD0315_2 might infect hosts via a Listeria LIPI-1-like cycle, with the help of a plasmid expressing the Hin DNA invertase to evade host immune responses.
Serum cytokine levels for predicting immune-related adverse events and the clinical response in lung cancer treated with immunotherapy
Authors: Zhao Ni , Yi Ye , Cao Wen , Fu Xiao , Mei Nan , Li Chunli 
Published: August 2022

BackgroundAt present, immunotherapy has become an important treatment for lung cancer. With the widespread use of immune checkpoint inhibitors (ICIs), we must be strict with the emergence of immune related adverse events (irAEs). There are also some patients who do not respond to immunotherapy. However, there was no biomarkers to predict the safety and efficacy of immunotherapy. The selection of immunotherapy beneficiaries contributes to improving the efficacy and safety of lung cancer treatment.MethodThe electronic medical records of 221 lung cancer patients with complete clinical data who received immunotherapy from the First Affiliated Hospital of Xi ‘an Jiaotong University from November 2020 to October 2021 were collected and followed up. IBM SPSS Statistic 26.0 and R 4.1.2 software were used for statistical analysis and mapping.Results1. A total of 221 lung cancer patients receiving immunotherapy were included in the study. Higher baseline levels of IL-1β (7.88 vs 16.16pg/mL,P=0.041) and IL-2 (1.28 vs 2.48pg/mL,P=0.001) were significantly associated with irAEs. Higher levels of IL-5 (2.64 vs 5.68pg/mL,P=0.013), IFN-α (1.70 vs 3.56pg/mL,P=0.004) and IFN-γ (6.14 vs 21.31pg/mL,P=0.022) after the first cycle therapy were associated with irAEs. There was no statistical significance between cytokines and irAEs after the second cycle therapy. Higher IL-5 levels in peripheral blood (9.50 vs 3.57pg/mL,P=0.032) were associated with the occurrence of irAEs after the third cycle therapy. 2.The efficacy of immunotherapy was assessed in 142 lung cancer patients. There was no statistical significance between baseline cytokine levels and clinical benefit. After the first cycle therapy, the level of serum cytokines had no statistical significance with the occurrence of immunotherapy clinical benefit. Lower serum levels of IL-10 (2.66 vs 1.26pg/mL,P=0.016) and IL-17 (8.47 vs 2.81pg/mL, P=0.015) were associated with clinical benefit after the second cycle therapy. Lower serum levels of IL-6 (10.19 vs 41.07pg/mL,P=0.013) and IL-8 (8.01 vs 17.22pg/mL,P=0.039) were associated with clinical benefit of immunotherapy after the third cycle therapy.Conclusion1. Baseline IL-1β and IL-2 levels in peripheral blood were associated with the occurrence of irAEs in lung cancer patients. The levels of IL-5, IFN-α and IFN-γ during treatment were associated with irAEs. 2. Baseline cytokine levels in peripheral blood were not associated with immunotherapy efficacy. The levels of IL-6, IL-8, IL-10, and IL-17 levels during treatment were associated with immunotherapy efficacy.