bluuebunny/crossref_metadata_2025_split huggingface dataset:
The vision of self-evolving computing systems
Authors: Weyns Danny , Bäck Thomas , Vidal Renè , Yao Xin , Belbachir Ahmed Nabil 
Published: May 2022

Computing systems are omnipresent; their sustainability has become crucial for our society. A key aspect of this sustainability is the ability of computing systems to cope with the continuous change they face, ranging from dynamic operating conditions, to changing goals, and technological progress. While we are able to engineer smart computing systems that autonomously deal with various types of changes, handling unanticipated changes requires system evolution, which remains in essence a human-centered process. This will eventually become unmanageable. To break through the status quo, we put forward an arguable opinion for the vision of self-evolving computing systems that are equipped with an evolutionary engine enabling them to evolve autonomously. Specifically, when a self-evolving computing systems detects conditions outside its operational domain, such as an anomaly or a new goal, it activates an evolutionary engine that runs online experiments to determine how the system needs to evolve to deal with the changes, thereby evolving its architecture. During this process the engine can integrate new computing elements that are provided by computing warehouses. These computing elements provide specifications and procedures enabling their automatic integration. We motivate the need for self-evolving computing systems in light of the state of the art, outline a conceptual architecture of self-evolving computing systems, and illustrate the architecture for a future smart city mobility system that needs to evolve continuously with changing conditions. To conclude, we highlight key research challenges to realize the vision of self-evolving computing systems.
Independent and Joint Associations of Tea Consumption and Smoking with Parkinson’s Disease Risk in Chinese Adults
Authors: Nie Jia ,   for the China Kadoorie Biobank (CKB) Collaborative Group, Liu Chunyu , Yu Canqing , Guo Yu , Pei Pei , Yang Ling , Chen Yiping , Du Huaidong , Zhu Kaifei , Schmidt Danile , Avery Daniel , Chen Junshi , Chen Zhengming , Lv Jun , Li Liming 
Published: May 2022

Background: Existing limited evidence suggests that smoking and tea consumption may be associated with a lower risk of Parkinson’s disease (PD). However, less is known about the independent and joint roles of these two habits, which are often clustered among Chinese, on PD risk. Objective: To prospectively examine the independent and joint association of tea consumption and smoking with the risk of PD. Methods: The China Kadoorie Biobank (CKB) study recruited 512,725 participants aged 30 to 79 years from ten areas across China since 2004. Information on smoking and tea consumption was collected at baseline, and PD cases were ascertained by linkage to the national health insurance system and death registry. Cox proportional hazards models were used to estimate the multivariable-adjusted hazard ratios (HRs) and corresponding 95%confidence intervals (CIs). Results: During a median of 10.8 years of follow-up, 922 PD cases were recorded. Compared with participants who never consumed tea, the HR (95%CI) for daily consumers was 0.68 (0.55, 0.84). Compared with participants who never or occasionally smoked, the HR (95%CI) for current smokers was 0.66 (0.53, 0.82). Those who had a clustering habit of smoking and tea consumption had a 38%(HR = 0.62; 95%CI: 0.49, 0.79) lower PD risk than those who consumed none. However, there were no statistically significant multiplicative or additive interaction for tea consumption and smoking on PD risk. Conclusion: We found that smoking and daily tea consumption were independently inversely associated with the risk of PD.
Complex housing partially mitigates low dose radiation-induced changes in brain and behavior in rats
Authors: Fiselier Anna , Mychasiuk Richelle , Muhammad Arif , Hossain Shakhawat , Ghose Abhijit , Kirkby Charles , Ghasroddashti Esmaeel , Kovalchuk Olga , Kolb Bryan 
Published: May 2022

Purpose: In recent years, much effort has been focused on developing new strategies for the prevention and mitigation of adverse radiation effects on healthy tissues and organs, including the brain. The brain is very sensitive to radiation effects, albeit as it is highly plastic. Hence, deleterious radiation effects may be potentially reversible. Because radiation exposure affects dendritic space, reduces the brain’s ability to produce new neurons, and alters behavior, mitigation efforts should focus on restoring these parameters. To that effect, environmental enrichment through complex housing (CH) and exercise may provide a plausible avenue for exploration of protection from brain irradiation. CH is a much broader concept than exercise alone, and constitutes exposure of animals to positive physical and social stimulation that is superior to their routine housing and care conditions. We hypothesized that CHs may lessen harmful neuroanatomical and behavioural effects of low dose radiation exposure. Methods: We analyzed and compared cerebral morphology in animals exposed to low dose head, bystander (liver), and scatter irradiation on rats housed in either the environmental enrichment condos or standard housing. Results: Enriched condo conditions ameliorated radiation-induced neuroanatomical changes. Moreover, irradiated animals that were kept in enriched CH condos displayed fewer radiation-induced behavioural deficits than those housed in standard conditions. Conclusions: Animal model-based environmental enrichment strategies, such as CH, are excellent surrogate models for occupational and exercise therapy in humans, and consequently have significant translational possibility. Our study may thus serve as a roadmap for the development of new, easy, safe and cost-effective methods to prevent and mitigate low-dose radiation effects on the brain.
Glucose Fluctuations Aggravate Myocardial Fibrosis via the Nuclear Factor-κB-Mediated Nucleotide-Binding Oligomerization Domain-Like Receptor Protein 3 Inflammasome Activation
Authors: Zhang Zhen-Ye , Dang Shi-Peng , Li Shan-Shan , Liu Ying , Qi Miao-Miao , Wang Ning , Miao Ling-Feng , Wu Ying , Li Xiao-Yan , Wang Chun-Xin , Qian Ling-Ling , Wang Ru-Xing 
Published: May 2022

BackgroundGlucose fluctuations may be associated with myocardial fibrosis. This study aimed to investigate the underlying mechanisms of glucose fluctuation-related myocardial fibrosis.MethodsStreptozotocin (STZ)-injected type 1 diabetic rats were randomized to five groups: the controlled blood glucose (CBG) group, uncontrolled blood glucose (UBG) group, fluctuated blood glucose (FBG) group, FBG rats injected with 0.9% sodium chloride (NaCl) (FBG + NaCl) group, and FBG rats injected with MCC950 (FBG + MCC950) group. Eight weeks later, left ventricular function was evaluated by echocardiography and myocardial fibrosis was observed by Masson trichrome staining. The primary neonatal rat cardiac fibroblasts were cultured with different concentrations of glucose in vitro.ResultsThe left ventricular function was impaired and myocardial fibrosis was aggravated most significantly in the FBG group compared with the CBG and UBG groups. The levels of interleukin (IL)-1β, IL-18, transforming growth factor-β1 (TGF-β1), collagen type 1 (collagen I), nuclear factor (NF)-κB, and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome were significantly increased in the FBG group. In vitro, the inhibition of NF-κB and inflammasome reversed these effects. In vivo, NLRP3 inhibition with MCC950 reversed left ventricular systolic dysfunction and myocardial fibrosis induced by glucose fluctuations.ConclusionGlucose fluctuations promote diabetic myocardial fibrosis by the NF-κB-mediated inflammasome activation.
Prognostic Impact of Multiple Lymphocyte-Based Inflammatory Indices in Acute Coronary Syndrome Patients
Authors: Li Qiuxuan , Ma Xiaoteng , Shao Qiaoyu , Yang Zhiqiang , Wang Yufei , Gao Fei , Zhou Yujie , Yang Lixia , Wang Zhijian 
Published: May 2022

BackgroundThe aim of this study was to evaluate the prognostic values of five lymphocyte-based inflammatory indices (platelet-lymphocyte ratio [PLR], neutrophil-lymphocyte ratio [NLR], monocyte-lymphocyte ratio [MLR], systemic immune inflammation index [SII], and system inflammation response index [SIRI]) in patients with acute coronary syndrome (ACS).MethodsA total of 1,701 ACS patients who underwent percutaneous coronary intervention (PCI) were included in this study and followed up for major adverse cardiovascular events (MACE) including all-cause death, non-fatal ischemic stroke, and non-fatal myocardial infarction. The five indices were stratified by the optimal cutoff value for comparison. The association between each of the lymphocyte-based inflammatory indices and MACE was assessed by the Cox proportional hazards regression analysis.ResultsDuring the median follow-up of 30 months, 107 (6.3%) MACE were identified. The multivariate COX analysis showed that all five indices were independent predictors of MACE, and SIRI seemingly performed best (Hazard ratio [HR]: 3.847; 95% confidence interval [CI]: [2.623–5.641]; p &lt; 0.001; C-statistic: 0.794 [0.731–0.856]). The addition of NLR, MLR, SII, or SIRI to the Global Registry of Acute Coronary Events (GRACE) risk score, especially SIRI (C-statistic: 0.699 [0.646–0.753], p &lt; 0.001; net reclassification improvement [NRI]: 0.311 [0.209–0.407], p &lt; 0.001; integrated discrimination improvement [IDI]: 0.024 [0.010–0.046], p &lt; 0.001), outperformed the GRACE risk score alone in the risk predictive performance.ConclusionLymphocyte-based inflammatory indices were significantly and independently associated with MACE in ACS patients who underwent PCI. SIRI seemed to be better than the other four indices in predicting MACE, and the combination of SIRI with the GRACE risk score could predict MACE more accurately.
Necropsy Validation of a Novel Method for Left Ventricular Mass Quantification in Porcine Transthoracic and Transdiaphragmal Echocardiography
Authors: Kristensen Charlotte Burup , Sattler Stefan Michael , Lubberding Anniek Frederike , Tfelt-Hansen Jacob , Jespersen Thomas , Hassager Christian , Mogelvang Rasmus 
Published: May 2022

IntroductionIncreased left ventricular mass (LVM) is one of the most powerful predictors of adverse cardiovascular events. Clinical evaluation requires reliable, accurate and reproducible echocardiographic LVM-quantification to manage patients. For this purpose, we have developed a novel two-dimensional (2D) method based on adding the mean wall thickness to the left ventricular volume acquired by the biplane method of disks, which has recently been validated in humans using cardiac magnetic resonance as reference value. We assessed the hypothesis that the novel method has better accuracy than conventional one-dimensional (1D) methods, when compared to necropsy LVM in pigs.Materials and MethodsEchocardiography was performed during anesthesia in 34 Danish Landrace pigs, weight 47–59 kg. All pigs were euthanized, cardiac necropsy was performed and the left ventricle was trimmed and weighed for necropsy LVM. Trans-thoracic echocardiography was applied for parasternal images. Transdiaphragmal echocardiography was applied for the apical images, which are otherwise difficult to obtain in pigs. We compared the conventional 1D- and 2D-methods and the novel 2D-method to the LVM from cardiac necropsy.ResultsNecropsy LVM was 132 ± 11 g (mean ± SD). The novel method had better accuracy than other methods (mean difference ± 95% limits of agreement; coefficients of variation; standard error of the estimate, Pearson's correlation). Novel (−1 ± 20 g; 8%; 11 g; r = 0.70), Devereux (+26 ± 37 g; 15%; 33 g; r = 0.52), Area-Length (+27 ± 34 g; 13 %; 33 g; r = 0.63), Truncated Ellipsoid (+10 ± 30 g; 12%; 19 g; r = 0.63), biplane endo-/epicardial tracing (−3 ± 2 g; 10%; 14 g; r = 0.57). No proportional bias in linear regression was detected for any method, when compared to necropsy LVM.ConclusionWe confirm high accuracy of the novel 2D-based method compared to conventional 1D/2D-methods.
Suberoylanilide Hydroxamic Acid (SAHA) Treatment Reveals Crosstalk Among Proteome, Phosphoproteome, and Acetylome in Nasopharyngeal Carcinoma Cells
Authors: Huang Huichao , Fu Ying , Duan Yankun , Zhang Ye , Lu Miaolong , Chen Zhuchu , Li Maoyu , Chen Yongheng 
Published: May 2022

Suberoylanilide hydroxamic acid (SAHA), a famous histone deacetylase (HDAC) inhibitor, has been utilized in clinical treatment for cutaneous T-cell lymphoma. Previously, the mechanisms underlying SAHA anti-tumor activity mainly focused on acetylome. However, the characteristics of SAHA in terms of other protein posttranslational modifications (PTMs) and the crosstalk between various modifications are poorly understood. Our previous work revealed that SAHA had anti-tumor activity in nasopharyngeal carcinoma (NPC) cells as well. Here, we reported the profiles of global proteome, acetylome, and phosphoproteome of 5–8 F cells upon SAHA induction and the crosstalk between these data sets. Overall, we detected and quantified 6,491 proteins, 2,456 phosphorylated proteins, and 228 acetylated proteins in response to SAHA treatment in 5–8 F cells. In addition, we identified 46 proteins exhibiting both acetylation and phosphorylation, such as WSTF and LMNA. With the aid of intensive bioinformatics analyses, multiple cellular processes and signaling pathways involved in tumorigenesis were clustered, including glycolysis, EGFR signaling, and Myc signaling pathways. Taken together, this study highlighted the interconnectivity of acetylation and phosphorylation signaling networks and suggested that SAHA-mediated HDAC inhibition may alter both acetylation and phosphorylation of viral proteins. Subsequently, cellular signaling pathways were reprogrammed and contributed to anti-tumor effects of SAHA in NPC cells.
Sperm Autoantigenic Protein 17 Predicts the Prognosis and the Immunotherapy Response of Cancers: A Pan-Cancer Analysis
Authors: Tu Zewei , Peng Jie , Long Xiaoyan , Li Jingying , Wu Lei , Huang Kai , Zhu Xingen 
Published: May 2022

BackgroundSperm autoantigen protein 17 (SPA17) is a highly conserved mammalian protein that participates in the acrosome reaction during fertilization and is a recently reported member of the cancer-testicular antigen (CTA) family. It has been reported that the SPA17 expression is limited in adult somatic tissues and re-expressed in tumor tissues. Recently, studies have found that SPA17 regulates the progression of various cancers, but its role in cancer immunotherapy is not clear.MethodsThe pan-cancer and normal tissue transcriptional data were acquired from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) datasets. We explored the SPA17 pan-cancer genomic alteration analysis in the cBioPortal webtool. The Human Protein Atlas (HPA) and ComPPI websites were used to mine the SPA17 protein information. We performed a western blotting assay to validate the upregulated SPA17 expression in clinical glioblastoma (GBM) samples. The univariate Cox regression and Kaplan–Meier method were used to assess the prognostic role of SPA17 in pan-cancer. Gene Set Enrichment Analysis (GSEA) was used to search the associated cancer hallmarks with SPA17 expression in each cancer type. TIMER2.0 was the main platform to investigate the immune cell infiltrations related to SPA17 in pan-cancer. The associations between SPA17 and immunotherapy biomarkers were performed by Spearman correlation analysis. The drug sensitivity information from the Connectivity Map (CMap) dataset was downloaded to perform SAP17-specific inhibitor sensitivity analysis.FindingsSPA17 was aberrantly expressed in most cancer types and exhibited prognosis predictive ability in various cancers. In addition, our results also show that SPA17 was significantly correlated with immune-activated hallmarks (including pathways and biological processes), immune cell infiltrations, and immunoregulator expressions. The most exciting finding was that SPA17 could significantly predict anti-PDL1 and anti-PD1 therapy responses in cancer patients. Finally, specific inhibitors, like irinotecan and puromycin, which correlate with SPA17 expression in different cancer types, were also screened using Connectivity Map (CMap).ConclusionsOur results reveal that SPA17 was abnormally expressed in cancer tissues, and this expression pattern could be associated with immune cell infiltrations in tumor microenvironments. Clinically, SPA17 not only acted as a potent prognostic factor to predict the clinical outcomes of cancer patients but was also a promising immunotherapy predictive biomarker for cancer patients treated with immune-checkpoint inhibitors (ICIs).
Acutely Inhibiting AQP4 With TGN-020 Improves Functional Outcome by Attenuating Edema and Peri-Infarct Astrogliosis After Cerebral Ischemia
Authors: Sun Chengfeng , Lin Luyi , Yin Lekang , Hao Xiaozhu , Tian Jiaqi , Zhang Xiaoxue , Ren Yan , Li Chanchan , Yang Yanmei 
Published: May 2022

BackgroundIschemic stroke is one of the leading causes of human death and disability. Brain edema and peri-infarct astrocyte reactivity are crucial pathological changes, both involving aquaporin-4 (AQP4). Studies revealed that acute inhibition of AQP4 after stroke diminishes brain edema, however, its effect on peri-infarct astrocyte reactivity and the subacute outcome is unclear. And if diffusion-weighted imaging (DWI) could reflect the AQP4 expression patterns is uncertain.MethodsRats were subjected to middle cerebral artery occlusion (MCAO) and allocated randomly to TGN 020-treated and control groups. One day after stroke, brain swelling and lesion volumes of the rats were checked using T2-weighted imaging (T2-WI). Fourteen days after stroke, the rats successively underwent neurological examination, T2-WI and DWI with standard b-values and ultra-high b-values, apparent diffusion coefficient (ADC) was calculated correspondingly. Finally, the rats’ brains were acquired and used for glial fibrillary acidic protein (GFAP) and AQP4 immunoreactive analysis.ResultsAt 1 day after stroke, the TGN-020-treated animals exhibited reduced brain swelling and lesion volumes compared with those in the control group. At 14 days after stroke, the TGN-020-treated animals showed fewer neurological function deficits and smaller lesion volumes. In the peri-infarct region, the control group showed evident astrogliosis and AQP4 depolarization, which were reduced significantly in the TGN-020 group. In addition, the ultra-high b-values of ADC (ADCuh) in the peri-infarct region of the TGN-020 group was higher than that of the control group. Furthermore, correlation analysis revealed that peri-infarct AQP4 polarization correlated negatively with astrogliosis extent, and ADCuh correlated positively with AQP4 polarization.ConclusionWe found that acutely inhibiting AQP4 using TGN-020 promoted neurological recovery by diminishing brain edema at the early stage and attenuating peri-infarct astrogliosis and AQP4 depolarization at the subacute stage after stroke. Moreover, ADCuh could reflect the AQP4 polarization.
The Levels of Oxidized Phospholipids in High-Density Lipoprotein During the Course of Sepsis and Their Prognostic Value
Authors: Li Zhaohong , Luo Zengtao , Shi Xiaoqian , Pang Baosen , Ma Yingmin , Jin Jiawei 
Published: May 2022

PurposeTo examine the levels of 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero phosphatidylcholine (POVPC) and 1-palmitoyl-2-glutaroyl-sn-glycero-phosphatidylcholine (PGPC) (the oxidized phosphatidylcholines) in HDL during the course of sepsis and to evaluate their prognostic value.Materials and MethodsThis prospective cohort pilot study enrolled 25 septic patients and 10 healthy subjects from 2020 to 2021. The HDLs were extracted from patient plasmas at day 1, 3 and 7 after sepsis onset and from healthy plasmas (total 81 plasma samples). These HDLs were then subjected to examining POVPC and PGPC by using an ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) system. We further measured the levels of 38 plasma cytokines by Luminex and evaluated the correlation of HDL-POVPC level with these cytokines. Patients were further stratified into survivors and non-survivors to analyze the association of HDL-POVPC level with 28-day mortality.ResultsSeptic patients exhibited significant increase of HDL-POVPC at day 1, 3 and 7 after sepsis onset (POVPC-D1, p=0.0004; POVPC-D3, p=0.033; POVPC-D7, p=0.004, versus controls). HDL-PGPC was detected only in some septic patients (10 of 25) but not in healthy controls. Septic patients showed a significant change of the plasma cytokines profile. The correlation assay showed that IL-15 and IL-18 levels were positively correlated with HDL-POVPC level, while the macrophage-derived chemokine (MDC) level was negatively correlated with HDL-POVPC level. Furthermore, HDL-POVPC level in non-survivors was significantly increased versus survivors at day 1 and 3 (POVPC-D1, p=0.002; POVPC-D3, p=0.003). Area under ROC curves of POVPC-D1 and POVPC-D3 in predicting 28-day mortality were 0.828 and 0.851. POVPC-D1and POVPC-D3 were the independent risk factors for the death of septic patients (p=0.046 and 0.035).ConclusionsHDL-POVPC was persistently increased in the course of sepsis. POVPC-D1 and POVPC-D3 were significantly correlated with 28-mortality and might be valuable to predict poor prognosis.