bluuebunny/crossref_metadata_2025 huggingface dataset:
PRospective Evaluation of natriuretic peptide-based reFERral of patients with chronic heart failure in primary care (PREFER): a real-world study
Authors: Hobbs FD Richard , Hussain Rizwan I , Vitale Cristina , Pinto Yigal M , Bueno Hector , Lequeux Benoit , Pauschinger Matthias , Obermeier Michael , Ferber Philippe C , Gustafsson Finn
Published: October 2021

Objective

To assess current management practice of heart failure with reduced ejection fraction (HFrEF) in multinational primary care (PC) and determine whether N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP)-guided referral of HFrEF patients from PC to a cardiologist could improve care, defined as adherence to European Society of Cardiology (ESC) guideline-recommended pharmacotherapy.

Methods

PRospective Evaluation of natriuretic peptide-based reFERral of patients with chronic HF in PC (PREFER) study enrolled HFrEF patients from PC considered clinically stable and those with NT-pro-BNP ≥600 pg/mL were referred to a cardiologist for optimisation of HF treatment. The primary outcome of adherence to ESC HF guidelines after referral to specialist was assessed at the second visit within 4 weeks of cardiologist’s referral and no later than 6 months after the baseline visit. Based on futility interim analysis, the study was terminated early.

Results

In total, 1415 HFrEF patients from 223 PCs from 18 countries in Europe were enrolled. Of these, 1324 (96.9%) were considered clinically stable and 920 (65.0%) had NT-pro-BNP ≥600 pg/mL (mean: 2631 pg/mL). In total, 861 (60.8%) patients fulfilled both criteria and were referred to a cardiologist. Before cardiologist consultation, 10.1% of patients were on ESC guideline-recommended HFrEF medications and 2.7% were on recommended dosages of HFrEF medication (defined as ≥50% of ESC guideline-recommended dose). Postreferral, prescribed HFrEF drugs remained largely unchanged except for an increase in diuretics (+4.6%) and mineralocorticoid receptor antagonists (+7.9%). No significant increase in patients’ adherence to guideline-defined drug combinations (11.2% post-referral vs 10.1% baseline) or drug combinations and dosages (3.3% postreferral vs 2.7% baseline) was observed after cardiologist consultation.

Conclusions

PREFER demonstrates substantial suboptimal treatment of HFrEF patients in the real world. Referral of patients with elevated NT-pro-BNP levels from PC to cardiologist did not result in meaningful treatment optimisation for treatments with known mortality and morbidity benefit.
Valve disease and aortopathy associations of bicuspid aortic valve phenotypes differ between men and women
Authors: Granath Carl , Mohamed Salah A , Olsson Christian , Grattan Michael , Mertens Luc , Franco-Cereceda Anders , Björck Hanna M
Published: October 2021

Objective

Determine whether associations between bicuspid aortic valve (BAV) phenotypes, valve disease and aortopathy differ between sexes.

Methods

1045 patients with BAV (76.0% men, n=794) from two surgical centres were included in this cross-sectional study. Valve phenotype was classified intraoperatively as right–left (RL), right-non-coronary (RN), left-non-coronary (LN) or 2-sinus BAV. Echocardiography was used to determine type and degree of valve disease, and aortic dimensions. Aortic dilatation was defined as diameter ≥4.5 cm.

Results

RL was the most common phenotype (73.6%), followed by RN (16.2%), 2-sinus BAV (9.2%) and LN (1.1%), with no difference in phenotype distribution between men and women (p=0.634). Aortic valve insufficiency (AI) prevalence differed significantly with valve phenotype in men (p=0.047), with RL and LN having the highest prevalence (34.1% and 44.0%, respectively). In women, RN had a higher proportion of AI than RL (21.3% vs 7.3%, p=0.017). Men with RL had larger root dimensions, in particular at the sinus (mean difference 0.24 cm compared with RN, p=0.002). Men with 2-sinus BAV had the highest prevalence of root phenotype dilatation (7.0%, other phenotypes ≤2.3%, p=0.031), whereas women with 2-sinus BAV did not have root dilatation and smaller sinus dimensions (mean difference: 0.35 cm compared with RL, p=0.021). Aortic root segments were larger in men with AI compared with aortic stenosis (sinus mean difference: 0.40 cm, p<0.001). The difference was even larger in women (mean difference: 0.78 cm, p<0.001), and women with AI also had larger tubular segments (mean difference: 0.61 cm, p=0.001).

Conclusions

There are significant sex differences in clinical associations of BAV phenotypes, which should be considered in further studies on the role of phenotypes in individualised patient management.
TNFi is associated with positive outcome, but JAKi and rituximab are associated with negative outcome of SARS-CoV-2 infection in patients with RMD
Authors: Regierer Anne Constanze , Hasseli Rebecca , Schäfer Martin , Hoyer Bimba F , Krause Andreas , Lorenz Hanns-Martin , Pfeil Alexander , Richter Jutta , Schmeiser Tim , Schulze-Koops Hendrik , Strangfeld Anja , Voll Reinhard E , Specker Christof , Mueller-Ladner Ulf
Published: October 2021

Introduction

Several risk factors for severe COVID-19 specific for patients with inflammatory rheumatic and musculoskeletal diseases (RMDs) have been identified so far. Evidence regarding the influence of different RMD treatments on outcomes of SARS-CoV-2 infection is still poor.

Methods

Data from the German COVID-19-RMD registry collected between 30 March 2020 and 9 April 2021 were analysed. Ordinal outcome of COVID-19 severity was defined: (1) not hospitalised, (2) hospitalised/not invasively ventilated and (3) invasively ventilated/deceased. Independent associations between demographic and disease features and outcome of COVID-19 were estimated by multivariable ordinal logistic regression using proportional odds model.

Results

2274 patients were included. 83 (3.6%) patients died. Age, male sex, cardiovascular disease, hypertension, chronic lung diseases and chronic kidney disease were independently associated with worse outcome of SARS-CoV-2 infection. Compared with rheumatoid arthritis, patients with psoriatic arthritis showed a better outcome. Disease activity and glucocorticoids were associated with worse outcome. Compared with methotrexate (MTX), TNF inhibitors (TNFi) showed a significant association with better outcome of SARS-CoV-2 infection (OR 0.6, 95% CI0.4 to 0.9). Immunosuppressants (mycophenolate mofetil, azathioprine, cyclophosphamide and ciclosporin) (OR 2.2, 95% CI 1.3 to 3.9), Janus kinase inhibitor (JAKi) (OR 1.8, 95% CI 1.1 to 2.7) and rituximab (OR 5.4, 95% CI 3.3 to 8.8) were independently associated with worse outcome.

Conclusion

General risk factors for severity of COVID-19 play a similar role in patients with RMDs as in the normal population. Influence of disease activity on COVID-19 outcome is of great importance as patients with high disease activity—even without glucocorticoids—have a worse outcome. Patients on TNFi show a better outcome of SARS-CoV-2 infection than patients on MTX. Immunosuppressants, rituximab and JAKi are associated with more severe course.
Production performance and metabolic characteristics of cows fed whole plant faba bean silage in comparison with barley and corn silage
Authors: Guevara-Oquendo Victor H. , Christensen David A. , Refat Basim , Rodriguez-Espinosa Maria E. , Feng Xin , Yu Peiqiang
Published: October 2021

This study aims to determine the effect of partial (50% and 75%) and complete (100%) replacement of barley and corn silage with whole plant faba bean silage on milk production, feed intake and efficiency, digestibility, and rumen fermentation characteristics of high producing cows. A repeated 4 × 4 Latin square (early lactating cows: four cannulated and four non-cannulated) design was used. The silage used for four treatments were different: control diet (T0; 18.37% corn silage + 12.23% barley silage), diet one (T50; 9.18% corn silage + 6.12% barley silage + 15.30% faba bean silage), diet two (T75; 4.59% corn silage + 3.06% barley silage + 22.95% faba bean silage), and diet three (T100; 30.60% faba bean silage). The results showed that fat corrected milk (3.5% FCM) and energy corrected milk (ECM) were linearly increased with increasing level of whole plant faba bean silage in the diets. The starch digestibility was linearly decreased from 95.3% to 90.4% with increasing supplementation using faba bean silage. Rumen fermentation characteristics (pH, ammonia, volatile fatty acids) were similar among all the treatments. In conclusion, the inclusion of whole plant faba bean silage improved FCM, ECM, milk fat yield, and efficiency without negatively affecting the intake of dry matter. This study showed that whole plant faba bean silage can be used as an alternative feed for dairy cows.
The OPG/RANKL/RANK system modulates calcification of common carotid artery in simulated microgravity rats by regulating NF-κB pathway
Authors: Liu Huan , Ru Ning-Yu , Cai Yue , Lyu Qiang , Guo Chi-Hua , Zhou Ying , Li Shao-Hua , Cheng Jiu-Hua , Chang Jin-Rui , Ma Jin , Su Xing-Li
Published: October 2021

Functional and structural adaptation of common carotid artery could be one of the important causes of postflight orthostatic intolerance after microgravity exposure, the mechanisms of which remain unclear. Recent evidence indicates that long-term spaceflight increases carotid artery stiffness, which might present a high risk to astronaut health and postflight working ability. Studies have suggested that vascular calcification is a common pathological change in cardiovascular diseases that is mainly manifested as an increase in vascular stiffness. Therefore, this study investigated whether simulated microgravity induces calcification of common carotid artery and to elucidate the underlying mechanisms. Four-week-old hindlimb-unweighted (HU) rats were used to simulate the deconditioning effects of microgravity on cardiovascular system. We found that simulated microgravity induced vascular smooth muscle cell (VSMC) osteogenic differentiation and medial calcification, increased receptor activator of nuclear factor κB (NF-κB) ligand (RANKL) and RANK expression, and enhanced NF-κB activation in rat common carotid artery. In vitro activation of the RANK pathway with exogenous RANKL, a RANK ligand, increased RANK and osteoprotegerin (OPG) expression in HU rats. Moreover, the expression of osteogenic markers and activation of NF-κB in HU rats were further enhanced by exogenous RANKL but suppressed by the RANK inhibitor osteoprotegerin fusion protein (OPG-Fc). These results indicated that the OPG/RANKL/RANK system modulates VSMC osteogenic differentiation and medial calcification of common carotid artery in simulated microgravity rats by regulating the NF-kB pathway.
Force dynamics and the gravitational collapse of compact stellar objects
Authors: Bogadi Robert S. , Govender Megandhren , Moyo Sibusiso
Published: October 2021

We investigate the nature of the forces involved during the collapse of a compact stellar object such as an unstable neutron star. The collapse ensues from an initial static configuration described by the Vaidya–Tikekar solution until the time of formation of the horizon. As the object collapses it radiates energy to the exterior spacetime in the form of a radial heat flux. The matching of the interior to the exterior Vaidya spacetime determines the temporal behaviour of the solution. Utilizing a dynamical Tolman–Oppenheimer–Volkoff equation, we investigate the evolution of the various forces at play within the collapsing fluid sphere. A novel connection has been made between structurally fundamental quantities (forces) and the spacetime geometry of the gravitational formalism used.
Perfects Across Languages
Authors: Dahl Östen
Published: October 2021

The theoretical study of perfects tends to be based on data from European languages, particularly English. To find the proper place for perfects, we have to go beyond English to be able to separate what is idiosyncratic from what is generalizable. A central function of perfects is to speak of how the present is different from the past, especially from the immediate past. A perfect typically relates how a past state changes into the present one. Crosslinguistically, we find two major types of perfect: constructions involving the auxiliary verbs ‘be’ and ‘have’, common in Indo-European and neighboring families, and iamitives, which are the result of the grammaticalization of words meaning ‘already’. The status of iamitives is controversial. In this review, I argue that they can be separated both from ‘already’ and from European-style perfects but that it makes sense to postulate a more inclusive crosslinguistic perfect category.
Tumor Region Location and Classification Based on Fuzzy Logic and Region Merging Image Segmentation Algorithm
Authors: Zhao Tianyu , Dai Hang
Published: October 2021

Early diagnosis of tumor plays an important role in the improvement of treatment and survival rate of patients. However, breast tumors are difficult to be diagnosed by invasive examination, so medical imaging has become the most intuitive auxiliary method for breast tumor diagnosis. Although there is no universal perfect method for image segmentation so far, the consensus on the general law of image segmentation has produced considerable research results and methods. In this context, this paper focuses on the breast tumor image segmentation method based on CNN and proposes an improved DCNN method combined with CRF. This method can obtain the information of multiscale and pixels better. The experimental results show that, compared with DCNN without these methods, the segmentation accuracy is significantly improved.
SLCO4A1-AS1 Facilitates the Malignant Phenotype via miR-149-5p/STAT3 Axis in Gastric Cancer Cells
Authors: Li Qing , Zhang Dachuan , Wang Hui , Xie Jun , Peng Lei , Peng Yan , Zheng Xiao , Jiang Jingting
Published: October 2021

Solute carrier organic anion transporter family member 4A1 (SLCO4A1-AS1), a newly discovered lncRNA, may exert effects in tumors. Since its role in gastric cancer remains obscure, we sought to explore the mechanism of SLCO4A1-AS1 in gastric cancer. The relationship among SLCO4A1-AS1, miR-149-5p, and STAT3 was detected by bioinformatics, dual luciferase analysis, and Pearson’s test, and the expressions of these genes were determined by quantitative real-time PCR and Western blot. Moreover, CCK-8, flow cytometry, wound healing assay, and Transwell analysis were performed to verify the function of SLCO4A1-AS1 in gastric cancer. Rescue experiments were used to detect the role of miR-149-5p. The expressions of SLCO4A1-AS1 and STAT3 were increased, while the expression of miR-149-5p was suppressed in gastric cancer tissues and cell lines. In addition, STAT3 expression was negatively correlated with miR-149-5p expression but was positively correlated with SLCO4A1-AS1 expression. Overexpression of SLCO4A1-AS1 promoted cell viability, migration, invasion, and STAT3 expression but suppressed apoptosis, while knockdown of SLCO4A1-AS1 had the opposite effect. SLCO4A1-AS1 bound to miR-149-5p and targeted STAT3. Moreover, miR-149-5p mimic inhibited the malignant development of gastric cancer cells and obviously reversed the function of SLCO4A1-AS1 overexpression. Our research reveals that abnormally increased SLCO4A1-AS1 expression may be an important molecular mechanism in the development of gastric cancer.
Optimization of Lactic Acid Production from Pineapple By-Products and an Inexpensive Nitrogen Source Using Lactiplantibacillus plantarum strain 4O8
Authors: Ngouénam Joel Romial , Kaktcham Pierre Marie , Momo Kenfack Chancel Hector , Foko Kouam Edith Marius , Ngoufack François Zambou
Published: October 2021

Lactic acid (LA) is used in food, cosmetic, chemical, and pharmaceutical industries and has recently attracted much attention in the production of biodegradable polymers. The expensive substances including carbon and nitrogen sources involved in its fermentative synthesis and the increasing market demand of LA have prompted scientists to look for inexpensive raw materials from which it can be produced. This research was aimed at determining the optimum conditions of lactic acid (LA) production from pineapple by-products and an inexpensive nitrogen source using Lactiplantibacillus plantarum strain 4O8. After collection and preparation of the carbon source (pineapple by-products) and nitrogen sources (by-products from fish, chicken, and beer brewing industries), they were used for the formulation of 4 different media in terms of nitrogen sources. Then, the proximate compositions of promising nitrogen sources were determined. This was followed by the screening of factors (temperature, carbon source, nitrogen source, MgSO4, MnSO4, FeSO4, KH2PO4, and KHPO4) influencing the production of LA using the definitive plan. Lastly, the optimization process was done using the central composite design. The highest LA productions (

14.64
±
0.05
 
g
/
l

and

13.4
±
0.02
 
g
/
l

) were obtained in production medium supplemented with chicken and fish by-products, respectively, making them the most promising sources of nitrogen. The proximate analysis of these nitrogen sources revealed that their protein contents were

83.00
±
1.41
%

DM and

74.00
±
1.41
%

DM for chicken by-products and fish by-products, respectively. Concerning the screening of factors, temperature, nitrogen source, and carbon source were the factors that showed a major impact on LA production in the production medium containing chicken by-products as nitrogen source. A pineapple by-product concentration of 141.75 g/l, a nitrogen source volume of 108.99 ml/l, and a temperature of 30.89°C were recorded as the optimum conditions for LA production. The optimization led to a 2.73-fold increase in LA production when compared with the production medium without nitrogen source. According to these results, chicken by-products are a promising and an inexpensive nitrogen source that can be an alternative to yeast extract in lactic acid production.
A Rainwater Harvesting and Treatment System for Domestic Use and Human Consumption in Native Communities in Amazonas (NW Peru): Technical and Economic Validation
Authors: Morales Rojas Eli , Díaz Ortiz Edwin Adolfo , Medina Tafur Cesar Augusto , García Ligia , Oliva Manuel , Rojas Briceño Nilton B.
Published: October 2021

The inhabitants of Tunants and Yahuahua face water supply problems in terms of quantity and quality, leading to socio-environmental and health impacts in the areas. The objective of this research, therefore, is to determine the technical and economic feasibility of a proposal for a rainwater harvesting and treatment system for human consumption in the native communities. For the technical feasibility, monthly water demand per family was compared with the amount of water collected in the rainy and dry seasons. In addition, 16 physical, chemical, and microbiological parameters were evaluated at the inlet and outlet of the water system. The economic feasibility was determined by the initial investment and maintenance of the systems; with the benefits, we obtained the net present social value (NPSV), social internal rate of return (SIRR), and cost-effectiveness (CE). Technically, oxygenation and chlorination in the storage tanks allowed for water quality in physical, chemical, and microbiological aspects, according to the D.S. N° 031-2010-SA standard, in all cases. Finally, with an initial investment of S/2,600 and S/70.00 for annual maintenance of the system, it is possible to supply up to six people per family with an average daily consumption of 32.5 L per person. It is suggested that the system be used at scale in the context of native communities in north-eastern Peru.
Coefficient Bounds of Kamali-Type Starlike Functions Related with a Limacon-Shaped Domain
Authors: Murugusundaramoorthy Gangadharan , Shakeel Ayesha , Kutbi Marwan Amin
Published: October 2021

In this article, we familiarize a subclass of Kamali-type starlike functions connected with limacon domain of bean shape. We examine certain initial coefficient bounds and Fekete-Szegö inequalities for the functions in this class. Analogous results have been acquired for the functionsf−1andξ/fξand also found the upper bound for the second Hankel determinanta2a4−a32.
Effect of Amoxicillin and Clavulanate Potassium Combined with Bazhengsan on Pediatric Urinary Tract Infection
Authors: Zhang Shengjun , Wang Zhenghua , Xu Guoping
Published: October 2021

Objective. To explore the therapeutic effect of amoxicillin and clavulanate potassium combined with Bazhengsan on pediatric urinary tract infection (UTI). Methods. The data of 120 UTI children treated in Wuhan Xinzhou District People’s Hospital from February 2019 to February 2020 were retrospectively analyzed. They were equally split into experimental group (EG) and control group (CG) according to the order of admission. All children were treated with amoxicillin and clavulanate potassium for suspension (twice a day), and EG was additionally treated with one dose of Bazhengsan daily. Both groups were treated for 10 days. After treatment, the immune function indexes, inflammatory factor levels, and clinical efficacy were compared before and after treatment. Results. No remarkable differences in the general data such as blood routine and urine routine results were observed between the two groups before treatment (

P
>
0.05

). After treatment, EG achieved obviously better immune function indexes (

P
<
0.001

) and lower levels of inflammatory factors (

P
<
0.05

) compared with CG. Besides, the treatment effective rate in EG (96.7%) was higher than that in CG (

P
<
0.05

). Conclusion. Amoxicillin and clavulanate potassium combined with Bazhengsan can improve the immune function of UTI children and reduce the levels of inflammatory factors, with remarkable effects, which should be popularized in practice.
Long-Term Observations of Thickness Changes of Each Retinal Layer following Macular Hole Surgery
Authors: Tada Atsushi , Machida Shigeki , Hara Yuji , Ebihara Satoshi , Ishizuka Masahiko , Gonmori Mana
Published: October 2021

Purpose. To determine the long-term changes of the thickness of each retinal layer following macular hole (MH) surgery combined with internal limiting membrane (ILM) peeling. Method. The medical records of 42 eyes of 42 patients (41 to 86 years of age) who underwent MH surgery with ILM peeling between February 2016 and October 2018 were reviewed. A single surgeon operated on all patients, and all were followed for at least 24 months postoperatively. Spectral-domain optical coherence tomography (OCT) was performed to obtain retinal thickness maps of the parafoveal region corresponding approximately to the ILM peeled area. Each retinal layer was automatically segmented by the embedded software, and thickness maps were constructed for the total retinal layer (TRL), inner RL (IRL), middle RL (MRL), and outer RL (ORL). The averaged value of each retinal layer thickness was analyzed in the temporal/upper, temporal/lower, nasal/upper, and nasal lower quadrants. Results. The TRL thickness was significantly decreased in the temporal areas postoperatively. The IRL thickness thinned progressively and significantly until 6 months without further thinning in the temporal quadrants. The MRL thickness of all areas was significantly thicker than the baseline values at 0.5 months and then gradually decreased in the temporal regions. However, the thickening in the nasal regions returned to the baseline values after 1.5 months. The ORL decreased transiently relative to the baseline values at 0.5 months in all areas. Conclusions. The ILM peeling does not affect only the thickness of the inner retina but also the middle and outer retinae in the parafoveal region. The chronological changes of the thickness after surgeries varied among the retinal layers and macular regions.
A Mobile Bayesian Network Structure Learning Method Using Genetic Incremental K2 Algorithm and Random Attribute Order Technology
Authors: Xiao Ying , Wang Deyan , Gao Ya
Published: October 2021

The application of existing datasets to construct a probabilistic network has always been the primary research focus for mobile Bayesian networks, particularly when the dataset size is large. In this study, we improve the K2 algorithm. First, we relax the K2 algorithm requirements for node order and generate the node order randomly to obtain the best result in multiple random node order. Second, a genetic incremental K2 learning method is used to learn the Bayesian network structure. The training dataset is divided into two groups, and the standard K2 algorithm is used to find the optimal value for the first set of training data; simultaneously, three similar suboptimal values are recorded. To avoid falling into the local optimum, these four optimal values are mutated into a new genetic optimal value. When the second set of training data is used, only the best Bayesian network structure within the five abovementioned optimal values is identified. The experimental results indicate that the genetic incremental K2 algorithm based on random attribute order achieves higher computational efficiency and accuracy than the standard algorithm. The new algorithm is especially suitable for building Bayesian network structures in cases where the dataset and number of nodes are large.
Kinematics Study of Depth Jump on Male Triple Jumpers with Slope Run-Up
Authors: Ma Youbao
Published: October 2021

Objective. To explore the training methods of developing the special strength of Chinese male triple jumpers through the experimental study of nine male triple-jumpers who performed step takeoff and depth long jump on the force platform. Methods. Through the combination of high-velocity shooting and a three-dimensional force measuring platform, the data of the athletes’ full run-up and depth jump landing, horizontal velocity, vertical velocity, takeoff time, landing angle, takeoff angle, and strength were obtained. In this study, the kinematics characteristics of four slopes with different slopes of 25 cm and 35 cm were studied. Kinematics’ data was measured by a high-velocity video camera. Results. The vertical velocity of the 35 cm platform is obviously less than that of the 25 cm platform

p
<
0.01

. The 25 cm platform is better at developing vertical, rapid takeoff ability, especially the fourth slope of this height, which is the fastest from horizontal velocity and vertical speed. All the depth jump practice ground angles are larger than the whole step jump, and the off-ground angle is smaller than the step jump, the takeoff time is larger than the step jump, which indicates that the athletes takeoff range is larger and the takeoff time is longer, and the results are in greater stimulation intensity of lower limb muscles. Conclusion. The 25 cm high platform depth jump exercise has achieved a better takeoff effect. Among the four slope depth jump exercises on this high platform, the 6.84 slope takeoff effect is the best.
Identification of Epithelial-Mesenchymal Transition- (EMT-) Related LncRNA for Prognostic Prediction and Risk Stratification in Esophageal Squamous Cell Carcinoma
Authors: Wang Peipei , Chen Yueyun , Zheng Yue , Fu Yang , Ding Zhenyu
Published: October 2021

Background. Epithelial-mesenchymal transition (EMT) is significantly associated with the invasion and development of esophageal squamous cell carcinoma (ESCC). However, the importance of EMT-related long noncoding RNA (lncRNA) is little known in ESCC. Methods. GSE53624 (

N
=
119

) and GSE53622 (

N
=
60

) datasets retrieved from the Gene Expression Omnibus (GEO) database were used as training and external validation cohorts, respectively. GSE53624 and GSE53622 datasets were all sampled from China. Then, the prognostic value of EMT-related lncRNA was comprehensively investigated by weighted coexpression network analysis (WGCNA) and COX regression model. Results. High expression of PLA2G4E-AS1, AC063976.1, and LINC01592 significantly correlated with the favorable overall survival (OS) of ESCC patients, and LINC01592 had the greatest contribution to OS. Importantly, ESCC patients were divided into low- and high-risk groups based on the optimal cut-off value of risk score estimated by the multivariate COX regression model of these three lncRNA. Patients with high risk had a shorter OS rate and restricted mean survival time (RMST) than those with low risk. Moreover, univariate and multivariate COX regression revealed that risk stratification, age, and TNM were independent prognostic predictors, which were used to construct a nomogram model for individualized and visualized prognosis prediction of ESCC patients. The calibration curves and time-dependent ROC curves in the training and validation cohorts suggested that the nomogram model had a good performance. Interestingly, clear trends indicated that risk score positively correlated with tumor microenvironment (TME) scores and immune checkpoints TIGIT, CTLA4, and BTLA. In addition, the Kyoto Encyclopedia of Genes and Genomes (KEGG) showed that PLA2G4E-AS1, AC063976.1, and LINC01592 were primarily associated with TNF signaling pathway, NF-kappa B signaling pathway, and ECM-receptor interaction. Conclusion. We developed EMT-related lncRNA PLA2G4E-AS1, AC063976.1, and LINC01592 for prognostic prediction and risk stratification of Chinese ESCC patients, which might provide deep insight for personalized prognosis prediction in Chinese ESCC patients and be potential biomarkers for designing novel therapy.
Netting Gut Disease: Neutrophil Extracellular Trap in Intestinal Pathology
Authors: Chen Kai , Shao Li-Hua , Wang Feng , Shen Xiao-Fei , Xia Xue-Feng , Kang Xing , Song Peng , Wang Meng , Lu Xiao-Feng , Wang Chao , Hu Qiong-Yuan , Liu Song , Guan Wen-Xian
Published: October 2021

Many gut disease etiologies are attributed to the presence of robust inflammatory cell recruitment. The recruitment of neutrophils plays a vital role in inflammatory infiltration. Neutrophils have various antimicrobial effector mechanisms, including phagocytosis, oxidative burst, and degranulation. It is suggested that neutrophils could release neutrophil extracellular traps (NETs) to kill pathogens. However, recent evidence indicates that neutrophil infiltration within the gut is associated with disrupted local immunological microenvironment and impaired epithelial barrier. Growing evidence implies that NETs are involved in the progression of many diseases, including cancer, diabetes, thrombosis, and autoimmune disease. Increased NET formation was found in acute or chronic conditions, including infection, sterile inflammation, cancer, and ischemia/reperfusion injury (IRI). Here, we present a comprehensive review of recent advances in the understanding of NETs, focusing on their effects in gut disease. We also discuss NETs as a potential therapeutic target in gut disease.
Characterization and Study of Gene Expression Profiles of Human Periodontal Mesenchymal Stem Cells in Spheroid Cultures by Transcriptome Analysis
Authors: Suga Takenori , Usui Michihiko , Onizuka Satoru , Sano Kotaro , Sato Tsuyoshi , Nakazawa Kohji , Ariyoshi Wataru , Nishihara Tatsuji , Nakashima Keisuke
Published: October 2021

A spheroid is known as a three-dimensional culture model, which better simulates the physiological conditions of stem cells. This study is aimed at identifying genes specifically expressed in spheroid-cultured human periodontal ligament mesenchymal stem cells (hPDLMSCs) using RNA-seq analysis to evaluate their functions. Transcriptome analysis was performed using spheroid and monolayer cultures of hPDLMSCs from four patients. Cluster and Gene Ontology analyses revealed that genes involved in cell-cell adhesion as well as the G2/M and G1/S transitions of mitotic cell cycles were strongly expressed in the monolayer culture group. However, genes involved in the negative regulation of cell proliferation, histone deacetylation, and bone morphogenetic protein signaling were strongly expressed in the spheroid culture group. We focused on the transcription factor nuclear receptor subfamily 4 group A member 2 (NR4A2) among the genes that were strongly expressed in the spheroid culture group and analyzed its function. To confirm the results of the transcriptome analysis, we performed real-time polymerase chain reaction and western blotting analyses. Interestingly, we found that the mRNA and protein expressions of NR4A2 were strongly expressed in the spheroid-cultured hPDLMSCs. Under osteogenic differentiation conditions, we used siRNA to knock down NR4A2 in spheroid-cultured hPDLMSCs to verify its role in osteogenesis. We found that NR4A2 knockdown significantly increased the levels of mRNA expression for osteogenesis-related genes alkaline phosphatase (ALP), Osteopontin (OPN), and type 1 collagen (COL1) (Student’s paired

t

-test,

p
<
0.05

). ALP activity was also significantly increased when compared to the negative control group (Student’s paired

t

-test,

p
<
0.05

). Additionally, spheroid-cultured hPDLMSCs transfected with siNR4A2 were cultured for 12 days, resulting in the formation of significantly larger calcified nodules compared to the negative control group (Student’s paired

t

-test,

p
<
0.05

). On the other hand, NR4A2 knockdown in hPDLMSC spheroid did not affect the levels of chondrogenesis and adipogenesis-related genes under chondrogenic and adipogenic conditions. These results suggest that NR4A2 negatively regulates osteogenesis in the spheroid culture of hPDLMSCs.
Financial Credit Risk Control Strategy Based on Weighted Random Forest Algorithm
Authors: Yangyudongnanxin Guo
Published: October 2021

In order to improve the effectiveness of financial credit risk control, a financial credit risk control strategy based on weighted random forest algorithm is proposed. The weighted random forest algorithm is used to classify the financial credit risk data, construct the evaluation index system, and use the analytic hierarchy process to evaluate the financial credit risk level. The targeted risk control strategies are taken according to different risk assessment results. We compared the proposed method with two other methods, and the experimental results show that the proposed method has higher classification accuracy of financial credit data and the risk assessment threshold is basically consistent with the actual results.
On
Ł

℘
,
℘
−
1
,
…
,
1

Labelings of Circulant Graphs
Authors: Mageshwaran K. , Ahmad Ali , Unyong Bundit , Kalaimurugan G. , Gopinath S.
Published: October 2021

An

m

-

Ł

℘
,
℘
−
1
,
…
,
1

labeling of a simple graph

G

is a mapping

τ

from the vertex set

∨

G

to

0,1
,
…
,
m

such that

τ

u

−
τ

v

≥
℘
+
1
−
d

u
,
v

,

∀
u
,
v
∈
∨

G

, where length of the shortest route connecting

u

and

v

is represented by

d

u
,
v

. The smallest

m

for which there exists a

m

-

Ł

℘
,
℘
−
1
,
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,
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labeling of

G

is known as the

Ł

℘
,
℘
−
1
,
…
,
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labeling number of

G

, and it is described by

λ

℘

G

. We define

m

-

Ł

′

℘
,
℘
−
1
,
…
,
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as the same as the

m

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Ł

℘
,
℘
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,
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,
1

labeling if

τ

is one to one. The

Ł

′

℘
,
℘
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,
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labeling number of

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represented by

λ

℘
,
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−
1
,
…
,
1

′

G

and is called minimum span. In this paper, we prove that the circulant graphs with specified generating sets admit

m

-

Ł

℘
,
℘
−
1
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and

m

-

Ł

′

℘
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labeling and also find

λ

℘

G

and

λ

℘
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,
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′

G

. Moreover, we find the

Ł

℘
,
℘
−
1
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,
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labeling number of any simple graph with diameter less than

℘

.
Clinical and Imaging Study of Repetitive Transcranial Magnetic Stimulation in the Treatment of Morphine Dependence Through mGluR5/TDP43/NR2B Pathway
Authors: Li Xin , Li Congyan , Yu Jia’nan , Ji Qing , Wang Wei , Peng Ying , Zhu Xiaofeng , Liu Jiguang
Published: October 2021

Morphine is tolerable after long-term use. After long-term use, it will have a great impact on the human body, and the treatment effect is not good. In recent years, the continuous development of repetitive transcranial magnetic stimulation (rTMS) treatment technology has made a treatment. Drug-resistant morphine dependence has a breakthrough. In this article, to study the effect of repeated transcranial magnetic stimulation in the treatment of morphine dependence through mGluR5/TDP43/NR2B pathway, experiments were carried out on rats to compare the changes in the images of rats after different periods of morphine use and their effects on morphine withdrawal. During the period, the performance of rats provides a reference for repeated transcranial stimulation to treat morphine dependence. According to the experimental results, after stopping morphine, withdrawal from the rats, irritable acts, and patience diminished. This is a decrease of more than 50% in comparison with the one of the normal group. There was a different degree of variability in the treatment images of mGluR5/TDP43 and so on after rTMS treatment, and the changes were large. These reductions in detoxification responses in rodents suggest that rTMS serves an instrumental role in the prevention and treatment of phosphorylation related to morphine dependence.
Retinal Lineage Therapeutic Specific Effect of Human Orbital and Abdominal Adipose-Derived Mesenchymal Stem Cells
Authors: Krief Bryan , Algor Shira Weisthal , Nakdimon Itay , Elhikis Ayala , Benhamou Moshe , Kadmon Anouk Savir , Keren Shay , Ohana Oded , Feldman Ilan , Cnaan Ran Ben , Leibovitch Igal , Loewenstein Anat , Barak Adiel , Barzelay Aya
Published: October 2021

Retinal degenerative diseases are one of the main causes of complete blindness in aged population. In this study, we compared the therapeutic potential for retinal degeneration of human mesenchymal stem cells derived from abdominal subcutaneous fat (ABASCs) or from orbital fat (OASCs) due to their accessibility and mutual embryonic origin with retinal tissue, respectively. OASCs were found to protect RPE cells from cell death and were demonstrated to increase early RPE precursor markers, while ABASCs showed a raise in retinal precursor marker expression. Subretinal transplantation of OASCs in a mouse model of retinal degeneration led to restoration of the RPE layer while transplantation of ABASCs resulted in a significant restoration of the photoreceptor layer. Taken together, we demonstrated a lineage-specific therapeutic effect for either OASCs or ABASCs in retinal regeneration.
lncRNA-KCNQ1OT1: A Potential Target in Exosomes Derived from Adipose-Derived Stem Cells for the Treatment of Osteoporosis
Authors: Wang Shan-zheng , Jia Jun , Chen Chang-hong
Published: October 2021

Background. Osteoporosis is a worldwide medical and socioeconomic burden characterized by systemic impairment of bone strength and microstructure. Exosomes derived from adipose-derived stem cells (ADSCs-Exos) have been confirmed to play effective roles in the repair of various tissues and organs. This study was aimed at investigating the role of ADSCs-Exos and a novel long noncoding RNA KCNQ1OT1 played in osteoporosis as well as the underlying mechanism. Methods. Primary osteoblasts were treated with different doses of tumor necrosis factor-α (TNF-α) (0, 1, 2.5, 5, and 10 ng/ml) and then cocultured with ADSCs-Exos or exosome-derived from lnc-KCNQ1OT1-modified ADSCs (KCNQ1OT1-Exos). The expression of miRNA-141-5p (miR-141-5p) and lnc-KCNQ1OT1 was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression of cleaved-caspase-3, caspase-3, and Bax was determined by Western blot. Cell viability and apoptosis were assessed by Cell Counting Kit-8 (CCK-8) and flow cytometry analysis, respectively. The binding sites between KCNQ1OT1 and miR-141-5p were validated by dual-luciferase reporter assay. Results. TNF-α dose-dependently increased miR-141-5p expression, inhibited viability, and promoted apoptosis of osteoblasts. However, miR-141-5p silencing or cocultured with ADSCs-Exos attenuated these effects. In addition, KCNQ1OT1-Exos could more significantly attenuate the induced cytotoxicity and apoptosis compared to ADSCs-Exos. Moreover, miR-141-5p was confirmed as the target of KCNQ1OT1 by luciferase reporter assay. Conclusions. ADSCs-Exos can attenuate cytotoxicity and apoptosis of TNF-α-induced primary osteoblasts. KCNQ1OT1-Exos have a more significant inhibitory effect compared to ADSCs-Exos by the function of sponging miR-141-5p, suggesting that KCNQ1OT1-Exos can be promising agents in osteoporosis treatment.
Artificial Intelligence-based MRI Images for Brain in Prediction of Alzheimer's Disease
Authors: Bi Xiaowang , Liu Wei , Liu Huaiqin , Shang Qun
Published: October 2021

The study aimed to explore the accuracy and stability of Deep metric learning (DML) algorithm in Magnetic Resonance Imaging (MRI) examination of Alzheimer's Disease (AD) patients. In this study, MRI data of patients obtained were from Alzheimer's Disease Neuroimaging Initiative (ADNI) database (A total of 180 AD cases, 88 women, 92 men; 188 samples in healthy conditions (HC), including 90 females and 98 males. 210 samples of mild cognitive impairment (MCI), 104 females and 106 males). On the basis of deep learning, an early AD diagnosis system was constructed using CNN (Convolutional Neural Network) and DML algorithms. Then, the system was used to classify AD, HC, and MCI, and the two algorithms were compared for the accuracy and stability of in classification of MRI images. It was found that in the classification of AD and HC, the classification accuracy and sensitivity of the deep measurement learning model are both 0.83, superior to the CNN model; in terms of specificity, the classification specificity of the DML model was 0.82, slightly lower than that of the CNN model; and that in the classification of MCI and HC, the classification accuracy and sensitivity of the DML model was 0.65, superior to the CNN model; and in terms of specificity, the classification specificity of the DML model was 0.66, slightly lower than that of the CNN model. It suggested that the DML model demonstrated better classification effects on early AD patients. The loss curve analysis results showed that, for classification of AD and HC or MCI and HC, the DML algorithm can improve the convergence speed of the AD early prediction model. Therefore, the DML algorithm can significantly improve the clarity and quality of MRI images, elevate the classification accuracy and stability of early AD patients, and accelerate the convergence of the model, providing a new way for early prediction of AD.
Advances in Experimental and Clinical Research of the Gouty Arthritis Treatment with Traditional Chinese Medicine
Authors: Liang Huan , Deng Pin , Ma Yu-Feng , Wu Yan , Ma Zhan-Hua , Zhang Wei , Wu Jun-De , Qi Yin-Ze , Pan Xu-Yue , Huang Fa-Sen , Lv Si-Yuan , Han Jing-Lu , Dai Wen-Da , Chen Zhaojun
Published: October 2021

Gouty arthritis (GA) is a multifactorial disease whose pathogenesis is utterly complex, and the current clinical treatment methods cannot wholly prevent GA development. Western medicine is the primary treatment strategy for gouty arthritis, but it owns an unfavorable prognosis. Therefore, the prevention and treatment of GA are essential. In China, traditional Chinese medicine (TCM) has been adopted for GA prevention and treatment for thousands of years. Gout patients are usually treated with TCM according to their different conditions, and long-term results can be achieved by improving their physical condition. And TCM has been proved to be an effective method to treat gout in modern China. Nevertheless, the pharmacological mechanism of TCM for gout is still unclear, which limits its spread. The theory of prevention and treatment of gout with TCM is more well acknowledged in China than in abroad. In this article, Chinese herbs and ancient formula for gout were summarized first. A total of more than 570 studies published from 2004 to June 2021 in PubMed, Medline, CNKI, VIP, Web of Science databases and Chinese Pharmacopoeia and traditional Chinese books were searched; the current status of TCM in the treatment of GA was summarized from the following aspects: articular chondrocyte apoptosis inhibition, antioxidative stress response, inflammatory cytokine levels regulation, uric acid excretion promotion, immune function regulation, uric acid reduction, and intestinal flora improvement in subjects with gout. The literature review concluded that TCM has a specific curative effect on the prevention and treatment of GA, particularly when combined with modern medical approaches. However, lacking a uniform definition of GA syndrome differentiation and the support of evidence-based medicine in clinical practice have provoked considerable concern in previous studies, which needs to be addressed in future research.
Association between Serum Prolactin Levels and Neurodegenerative Diseases: Systematic Review and Meta-Analysis
Authors: Duc Nguyen Hai , Hoang Ngoc Minh Hong , Ko Myeonghee , Seo Dongjin , Kim Shinhyun , Jo Won Hee , Bae Jung-Woo , Kim Min-Sun
Published: October 2021

Introduction: Prolactin (PRL) exerts inflammatory and anti-inflammatory properties and is also thought to play an important role in the pathogenesis of neurodegenerative diseases (NDs). However, serum PRL levels in patients with NDs were inconsistent in the research literature. Objective: We aimed to assess the serum PRL levels in patients with NDs. Methods: Electronic databases, including MEDLINE, Embase, Cochrane Library database, clinicaltrials.gov, Web of Science, and Google Scholar, and reference lists of articles were searched up to December 31, 2020. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effect or random-effect model analysis. Results: A total of 36 comparisons out of 29 studies (3 RCTs and 26 case controls) focusing on NDs (including Parkinson’s disease, Alzheimer’s disease, Huntington’s disease [HD], multiple sclerosis [MS], and epilepsy) were reported. The meta-analysis showed that there was no statistically significant difference in serum PRL levels between patients with NDs and healthy controls (SMD = 0.40, 95% CI: −0.16 to 0.96, p = 0.16). Subgroup analysis showed that serum PRL levels in patients with HD and MS were higher than those of healthy controls. Furthermore, patients with NDs aged <45 years had higher serum PRL levels (SMD = 0.97, 95% CI: 0.16–1.78, p = 0.018) than healthy controls. High serum PRL levels were found in subgroups such as the microenzymatic method, Asia, and the Americas. Conclusions: Our meta-analysis showed serum PRL levels in patients with HD and MS were significantly higher than those in healthy controls. Serum PRL levels were associated with age, region, and detection method. Other larger sample studies using more uniform detection methods are necessary to confirm our results.