bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracellular Vesicles of Mesenchymal Stromal Cells Can be Taken up by Microglial Cells and Partially Prevent The Stimulation Induced by β-Amyloid
Authors: Kaniowska Dorota , Wenk Kerstin , Rademacher Phil , Weiß Ronald , Fabian Claire , Schulz Isabell , Guthardt Max , Lange Franziska , Greiser Sebastian , Schmidt Matthias , Braumann Ulf-Dietrich , Emmrich Frank , Köhl Ulrike , Jaimes Yarúa 
Published: June 2021

Abstract
Mesenchymal stromal/stem cells (MSCs) have great capacity for immune regulation. MSCs provide protective paracrine effects, which are partially exerted by extracellular vesicles (EVs). It has been reported that MSCs-derived EVs (MSC-EVs) contain soluble factors, such as cytokines, chemokines, growth factors and even microRNAs, which confer them similar anti-inflammatory and regenerative effects to MSCs. Moreover, MSCs modulate microglia activation through a dual mechanism of action that relies both on cell contact and secreted factors. Microglia cells are the central nervous system immune cells and the main mediators of the inflammation leading to neurodegenerative disorders. Here, we investigated whether MSC-EVs affect the activation of microglia cells by β-amyloid aggregates. We show that the presence of MSC-EVs can prevent the upregulation of pro-inflammatory mediators such as tumor necrosis factor (TNF)-α and nitric oxide (NO). Both are up-regulated in neurodegenerative diseases representing chronic inflammation, as in Alzheimer’s disease. We demonstrate that MSC-EVs are internalized by the microglia cells. Further, our study supports the use of MSC-EVs as a promising therapeutic tool to treat neuroinflammatory diseases.
QoS-aware Resource Allocation for Live Streaming in Edge-Clouds Aided HetNets Using Stochastic Network Calculus
Authors: Mirzaei Abbas 
Published: June 2021

Abstract
Mobile edge computing (MEC) is a key feature of next generation mobile networks aimed at providing a variety of services for different applications by performing related processing tasks closer to the user equipment. Edge clouds can be installed as an interface between the cellular networks and the core to provide the required services based on the known concept of the MEC networks. Nonetheless, the problem of green networking will be of great importance in such networks. This paper presents an energy-efficient stochastic network calculus (SNC) framework to control MEC data flows. In accordance with the entrance processes of different QoS-class data flows, closed-form problems were formulated to determine the correlation between resource utilization and the violation probability of each data flow. Also, in the access layer, this paper proposes a dynamic user association and resource allocation approach which maximizes the overall energy efficiency of cache-enabled cellular networks in addition to provide the superior fairness level for UEs. In this energy-cooperative approach, the power can be shared among the cells using a grid network. This model also performs routing in the multi-hop backhaul to efficiently use the existing infrastructure of small cell networks for simultaneous dual-hop transmissions. The simulation results exhibit that the proposed approach can effectively increase the user throughput and the total power efficiency while guaranteeing the acceptable fairness level for uniform and hotspot UE distribution models. It also proved that the energy utilization index and the system data rate can be significantly improved.
Gut Microbiome Diversity and Specific Composition During Immunotherapy in Japanese Responders with Non-Small Cell Lung Cancer
Authors: Shoji Fumihiro , Yamaguchi Masafumi , Okamoto Masaki , Takamori Shinkichi , Kozuma Yuka , Toyokawa Gouji , Yamazaki Koji , Okamoto Tatsuro , Takenoyama Mitsuhiro , Shimokawa Mototsugu , Takeo Sadanori , Maehara Yoshihiko 
Published: June 2021

Abstract

Cancer immunotherapy including immune checkpoint inhibitors (ICI) has revolutionized non-small cell lung cancer (NSCLC) therapy. Recently, the microbiome status before initiation of ICI therapy has been emphasized as a predictive biomarker in patients undergoing ICI therapy. However, the microbiome diversity and composition during ICI therapy is unknown. This multicenter, prospective observational study analyzed both saliva and feces from 28 patients with NSCLC. We performed 16S ribosomal RNA gene sequencing, then analyzed associations of oral and gut microbiome diversity or composition with ICI response. Seventeen patients (responders) had a partial ICI response, and the remaining 11 patients (non-responders) had stable or progressive disease. At the genus level, the alpha diversity of the gut microbiome was significantly greater in ICI responders than in non-responders (Chao 1, p = 0.0174; PD whole tree, p = 0.0219; observed species, p = 0.0238; Shannon, p = 0.0362), while the beta diversity of the gut microbiome was significantly lower in ICI responders (principal coordinates analysis, p = 0.035). Compositional differences in the gut microbiome were observed between the two groups; in particular, Blautia was enriched in ICI responders, whereas RF32 unclassified was enriched in ICI non-responders. There were no significant differences between groups in the oral microbiome. This study revealed a strong association between gut microbiome diversity and ICI response in Japanese NSCLC patients. Moreover, specific gut microbiome compositions may influence the ICI response. These findings might be useful in identifying biomarkers to predict ICI response, as well as in developing biotic therapies to enhance the ICI response.
Plasma Levels of Receptor-interacting Protein Kinase 3 Is Associated With Postoperative Acute Kidney Injury in Acute DeBakey Type I Aortic Dissection.
Authors: Wang Lei , Zhong Guodong , Zhou Hao , Lv Xiaochai , Dong Yi , Wang Xiaoli , Dai Xiaofu , Xu Yanfang , Chen LiangWan 
Published: June 2021

Abstract
Background. Postoperative acute kidney injury (AKI) in acute Debakey type I aortic dissection (ADIAD) is common but has unclear pathogeneses and limited treatments. Receptor-interacting protein kinase 3 (RIP3), a mediator of necroptosis, is associated with human sepsis-induced and posttraumatic AKI, but its role in human postoperative AKI in ADIAD remains unclear. We assumed that RIP3 levels is associated with postoperative AKI in ADIAD.Methods. Plasma samples and the clinical data of continuous patients with ADIAD were collected prospectively. The patients were divided into three groups according to AKI stage postoperatively. The plasma RIP3 levels were compared among the groups, and the relationship between RIP3 and serum creatinine (sCr), inflammatory cytokines as well as clinical results were analyzed. Results. Eighty patients were enrolled. The postoperative and elevated RIP3 levels among the three groups were significantly different (P < 0.0001), both with a positive trend across the AKI stage (P for trend < 0.001), and they were also independent risk factors for postoperative AKI in ADIAD (OR=1.018 and 1.026, P < 0.05). The postoperative RIP3 levels were positively correlated with the aortic crossclamp time (R=0.253, P < 0.05); the peak values of sCr, procalcitonin, interleukin-6 and lactate postoperatively; the mechanical ventilation time; and the ICU stay time (R= 0.66, 0.369, 0.409, 0.397, 0.474 and 0.435, respectively; all P < 0.001). Plasma RIP3 level and sCr were comparable in diagnosing postoperative AKI in ADIAD (P = 0.898), and higher postoperative RIP3 level was associated with lower survival rate. Conclusion. The plasma RIP3 levels are associated with postoperative AKI, inflammatory response and clinical outcomes in ADIAD.
QTL Validation and Development of SNP-based High Throughput Molecular Markers Targeting a Genomic Region Conferring Narrow Root Cone Angle in Aerobic Rice Production Systems
Authors: Vinarao Ricky , Proud Christopher , Snell Peter , Fukai Shu , Mitchell Jaquie 
Published: June 2021

Abstract

BackgroundAerobic rice production (AP) is a potential solution to the imminent global water crisis as it consumes less water than traditional permanent water culture. Narrow root cone angle (RCA) and subsequent development of deeper rooting systems are considered AP adaptation traits by enabling water uptake at depth. Quantitative trait loci (QTL), such as qRCA4, contributing to RCA variation in AP systems have been previously identified. However, their usefulness depends on validation in a range of genetic backgrounds, development of associated molecular markers, and identification of possible donors in other subpopulations. Results Using three F2 bi-parental populations derived from IRAT109 crossed with three different genetic backgrounds, and genotypes with known qRCA composition, QTL validation were performed and molecular markers developed. qRCA4 was shown to be effective in multiple backgrounds, explaining 9.3-17.3% of the genotypic variation in the populations tested and the introgression of the favourable allele resulted in 11.7-15.1° narrower RCA. Novel kompetive allele specific PCR (KASP) molecular markers have been developed associated with narrow RCA. Core molecular marker quality metrics have shown robustness and breeding program specific utility of up to 83%. qRCA4 was further fine mapped into a 720 kb region. Analysis of candidate genes identified those related with plant response to abiotic stress stimulus together with root development. Available public database search found 178 potential donors representing major rice subpopulations and may be used readily by breeding programs. ConclusionThis study validated qRCA4’s effect in multiple genetic backgrounds further strengthening its value in improvement of rice genotypes for AP adaptation. Furthermore, the development of novel KASP markers has ensured the opportunity for its seamless introgression across pertinent breeding programs. Future research in metabolomic and transcriptomic analysis of QTL positive genotypes should improve the understanding of the physiological mechanisms underpinning narrow RCA and development of deeper rooting. Finally, this work provides the tools and opportunity to accelerate the development of genotypes with narrow RCA through marker assisted selection in breeding programs targeting AP, which may ultimately contribute to more sustainable rice production where water availability is limited.
Assessment of the Influence of Keratometry on Intraocular Lens Calculation Formulas in Long Axial Length Eyes
Authors: Yin Shengjie , Guo Chengyao , Qiu Kunliang , Ng Tsz Kin , Li Yuancun , Du Yali , Chen Bingyao , Wang Hongxi , Zhang Mingzhi 
Published: June 2021

Abstract
Purpose: Hyperopic surprises tend to occur in axial myopic eyes and other factors including corneal curvature have rarely been analyzed in cataract surgery, especially in eyes with long axial length (≥ 26.0 mm). Thus, the purpose of our study was to evaluate the influence of keratometry on four different formulas (SRK/T, Barrett Universal II, Haigis and Olsen) in intraocular lens (IOL) power calculation for long eyes.Methods: Retrospective case-series. 180 eyes with axial length (AL) ≥ 26.0 mm were divided into 3 keratometry (K) groups: K ≤ 42.0 D (Flat), K ≥ 46.0 D (Steep), 42.0 < K < 46.0 D (Average). Prediction errors (PE) were compared between different formulas. Multiple regression analysis was performed to investigate factors associated with the PE.Results: The mean absolute error was higher for all evaluated formulas in Steep group (ranging from 0.66 D to 1.02 D) than the Flat (0.34 D to 0.67 D) and Average groups (0.40 D to 0.74D). The median absolute errors predicted by Olsen formula were significantly lower than that predicted by Haigis formula (0.42 D versus 0.85 D in Steep and 0.29 D versus 0.69 D in Average) in Steep and Average groups (P = 0.012, P < 0.001, respectively). And the Olsen formula demonstrated equal accuracy to the Barrett II formula in Flat and Average groups. The predictability of the SRK/T formula was affected by the AL and K, while the predictability of Olsen and Haigis formulas was affected by the AL only. Conclusions: Steep cornea has more influence on the accuracy of IOL power calculation than the other corneal shape in long eyes. Overall, both the Olsen and Barrett Universal II formulas are recommended in long eyes with unusual keratometry.
The value of ROX index in predicting the outcome of high flow nasal cannula: a systematic review and meta-analysis
Authors: Junhai Zhen , Jing Yan , Shijin Gong , BeiBei Cao , Li Li 
Published: June 2021

Abstract
Background: High flow nasal cannula (HFNC) therapy is widely employed in acute hypoxemic respiratory failure (AHRF) patients. However, the techniques for predicting HFNC outcome remain scarce.Methods: PubMed, EMBASE, and Cochrane Library were searched until April 20, 2021. We included the studies that evaluated the potential predictive value of ROX (respiratory rate-oxygenation) index for HFNC outcome. This meta-analysis determined sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic score, diagnostic odds ratio (DOR), and pooled area under the summary receiver operating characteristic (SROC) curve.Results: We assessed nine studies with 1933 patients, of which 745 patients experienced HFNC failure. This meta-analysis found that sensitivity, specificity, PLR, NLR, diagnostic score, and DOR of ROX index in predicting HFNC failure were 0.67 (95% CI 0.57-0.76), 0.72 (95% CI 0.65-0.78), 2.4 (95% CI 2.0-2.8), 0.46 (95% CI 0.37-0.58), 1.65(95% CI 1.37-1.93), and 5.0 (95% CI 4.0-7.0), respectively. In addition, SROC was 0.75 (95% CI 0.71-0.79). Besides, our subgroup analyses revealed that ROX index had higher sensitivity and specificity for predicting HFNC failure in COVID-19 patients from non-European countries, while the acquisition time of 6 h after receiving HFNC had a lower sensitivity and specificity when compared to other times.Conclusions: This study demonstrated that ROX index could function as a novel potential marker to identify patients with a higher risk of HFNC failure. However, the prediction efficiency was moderate, and additional research is required to determine the optimal cut-off value and propel acquisition time of ROX index in the future.
Clinical Implication of Monitoring Circulating Tumor DNA in Untreated Non-Small-Cell Lung Cancer Patients
Authors: Lim Jun Hyeok , Shin Hyun-Tae , Oh Sekyung , Lee Seung Jae , Ryu Jeong-Seon 
Published: June 2021

Abstract
CtDNA has been utilized to monitor the clinical course of the patients of NSCLC who receive therapies targeting druggable mutations. However, despite providing valuable information on how NSCLC would naturally progress, the clinical utility of ctDNA for clinical-course monitoring and prediction of the treatment-naïve NSCLC patients without druggable mutations remain unknown. We longitudinally followed a total of 12 treatment-naïve NSCLC patients, who did not harbor EGFR and ALK mutations, by collecting clinical information, radiological data, and plasma samples. Changes in ctDNA levels and tumor burden (TB) were also compared with each other. Volume doubling time (VDT), and overall survival (OS) were analyzed regarding ctDNA detection at diagnosis. CtDNA was detected in the plasma of seven (58.3%) patients. Changes in ctDNA levels correlated with those in TB in a substantial fraction (57.1%) of patients and was also associated with brain metastasis, tumor necrosis, or pneumonia in other patients. In addition, the patients with ctDNA detection had shorter VDT (p = 0.039) and worse OS (p = 0.019) than those without ctDNA detection. The natural course of NSCLC progression can be monitored by measuring ctDNA levels. Detection of ctDNA at diagnosis can predict rapid tumor growth and poor survival of NSCLC patients.
Model Predictive Displacement Control Tuning for Tap-Water-Driven Muscle By Inverse Optimization with Adaptive Model Matching and Analysis of Contribution
Authors: Tsuruhara Satoshi , Inada Ryo , Ito Kazuhisa 
Published: June 2021

Abstract
The tap-water-driven McKibben muscle has many advantages and is expected to be applied in mechanical systems that require a high degree of cleanliness. However, the muscle has strong asymmetric hysteresis characteristics that depend on the load, and these problems prevent its widespread use. In this study, a novel control method - model predictive control with servomechanism based on inverse optimization with adaptive model matching - is applied to the muscle based on a high-precision mathematical model employing an asymmetric Bouc-Wen model. The experimental results show that the proposed approach achieves a high tracking performance at a reference frequency of 0.3 Hz, with a mean absolute error of 0.13 mm in the steady-state response. Furthermore, an easier controller tuning can be achieved. Additionally, the authors evaluate the contributions of the elements of the proposed method. The results show that the contribution of the adaptive system is higher than that of the servo system. Furthermore, the effectiveness of adaptive model matching is reconfirmed.
3x + 1 problem: Iterative operations neither cause loops nor diverge to infinity
Authors: Jiang Li 
Published: June 2021

Abstract
The 3x+1 problem is a problem of continuous iteration for integers. According to the basic theorem of arithmetic and the way of iteration, we derive a general formula for continuous iteration for odd integers. Through this formula, we can construct a loop iteration equation and obtain the result of the equation: the equation has only one positive integer solution. In addition, this general formula can be converted into a linear indeterminate equation. The process of solving this equation shows that the relationship between the iteration result and the odd number being iterated is linear. Extending this result to all positive even numbers, we get the answer to the 3x + 1 question.
Triglyceride-glucose Index Predicts 2-year Adverse Cardiovascular and Cerebrovascular Events in Patients With Type 2 Diabetes Mellitus and Non-st-segment Elevation Acute Coronary Syndrome Who Underwent Off-pump Coronary Artery Bypass Grafting
Authors: Chen Liang , Ding Xiao-Hang , Fan Kang-Jun , Gao Ming-Xin , Yu Wen-Yuan , Liu Hong-Li , Yu Yang 
Published: June 2021

Abstract
Background: Data on the relationship between the triglyceride glucose (TyG) index and prognosis after off-pump coronary artery bypass grafting (OPCABG) are limited. This retrospective observational study evaluated the association of the TyG index with prognosis in patients with type 2 diabetes mellitus (T2DM) and non-ST-segment elevation acute coronary syndrome (NSTE-ACS) who underwent OPCABG.Methods: A total of 1534 patients with T2DM who underwent OPCABG for NSTE-ACS were enrolled in this study. Patients were divided into lower and higher TyG index groups according to the optimal cutoff value of the TyG index for predicting the primary endpoint. The primary outcomes included the occurrence of major adverse cardiovascular and cerebrovascular events (MACCEs), which were defined as all-cause death, nonfatal myocardial infarction, nonfatal stroke and symptomatic graft stenosis or occlusion. The TyG index was calculated using the following equation: TyG index = ln (fasting triglyceride level [mg/dL] × fasting glucose level [mg/dL]/2).Results: The overall incidence of MACCEs was 10.7% with a median follow-up of 23.1 months. The optimal TyG index cutoff for predicting MACCEs was 9.42 (sensitivity 49.4%; specificity 71.2%; area under the curve 0.631; P < 0.001). The incidence of MACCEs increased with a 1-unit increase in the TyG index [HR 2.218, 95% CI (1.733-2.839), P < 0.001]. A TyG index greater than 9.42 was independently associated with a higher risk of MACCEs [HR 2.092, 95% CI (1.573-2.784), P < 0.001] and each component. Furthermore, the effect of TyG in increasing MACCEs was consistent across groups of age, sex, BMI, hypertension, LDL-C, oral hypoglycemic agents, LIMA, number of grafts and IABP groups, except in patients diagnosed with NSTEMI, treated with statins and prescribed insulin at discharge.Conclusion: The TyG index predicts future MACCEs independently of known cardiovascular risk factors, suggesting that the TyG index may be a useful marker for prognosis in patients with T2DM and NSTE-ACS who underwent OPCABG.
Economic Burden of Comorbid Chronic Conditions Among Survivors of Stroke in China: 10-Year Longitudinal Study
Authors: Zhang Ji , Song Suhang , Zhao Yang , Ma Gaoting , Jin Yinzi 
Published: June 2021

Abstract
Background: The coexistence of chronic diseases among people with stroke is common. However, little is known about the extent of incremental healthcare expenditures associated with having physically and psychologically chronic conditions among stroke survivors.Methods: We used the nationally representative data from the China Health and Nutrition Survey, including 36,076 participants enrolled as our analytic cohort of ten years of follow-up visits (2006, 2009, 2011, 2015). Chronic conditions include hypertension, diabetes, obesity, and impaired cognitive function. Two-part models were used to estimate the effect of comorbid chronic conditions on total annual healthcare expenditure, out-of-pocket (OOP) healthcare expenditure, and incidence of catastrophic healthcare expenditure (CHE).Results: Among survivors of stroke during 2006 to 2015, the prevalence rates of hypertension, diabetes, obesity and impaired cognitive function were 75.5%, 9,8%, 12.7% and 65.1%, significantly higher than those among adults without stroke history (27.9%, 2.7%, 10.0% and 41.2%). Having hypertension ($794.5, p=0.004), diabetes ($3978.5, p<0.001) were associated with the largest incremental total healthcare expenditures. Stroke survivors with diagnosed hypertension and diabetes had additional 5.7 (p<0.001) and 10.4 (p<0.001) percentage point of CHE rate, respectively. Total healthcare expenditures were $2413.0 (P<0.001) and $5151.7 (P<0.001) higher among patients with 2, and ≥3 chronic conditions, respectively, than those individuals with no chronic conditions.Conclusions: Excess expenditures associated with chronic diseases were substantial among stroke survivors. These results highlight the needs for both prevention and better management of multimorbidity among stroke survivors, which in turn may lower the financial burden of treating these concurrent comorbidities.
MTBAN: An Enhanced Variant Effect Predictor Based on a Deep Generative Model
Authors: Kim Ha Young , Jeon Woosung , Kim Dongsup 
Published: June 2021

Abstract
The development of an accurate and reliable variant effect prediction tool is important for research in human genetic diseases. A large number of predictors have been developed towards this goal, yet many of these predictors suffer from the problem of data circularity. Here we present MTBAN (Mutation effect predictor using the Temporal convolutional network and the Born-Again Networks), a method for predicting the deleteriousness of variants. We apply a form of knowledge distillation technique known as the Born-Again Networks (BAN) to a previously developed deep autoregressive generative model, mutationTCN, to achieve an improved performance in variant effect prediction. As the model is fully unsupervised and trained only on the evolutionarily related sequences of a protein, it does not suffer from the problem of data circularity which is common across supervised predictors. When evaluated on a test dataset consisting of deleterious and benign human protein variants, MTBAN shows an outstanding predictive ability compared to other well-known variant effect predictors. We also offer a user-friendly web server to predict variant effects using MTBAN, freely accessible at http://mtban.kaist.ac.kr. To our knowledge, MTBAN is the first variant effect prediction tool based on a deep generative model that provides a user-friendly web server for the prediction of deleteriousness of variants.