bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low-dose anti-VEGFR2 therapy promotes anti-tumor immunity in lung adenocarcinoma by down-regulating the expression of layilin on tumor-infiltrating CD8+T cells
Authors: Yang Biaolong , Deng Biaolong , Jiao Xiao-Dong , Qin Bao-Dong , Lu Yi , Zhang Weiqi , Guo Yixian , Chen Shiqi , Li Dan , Li Bin , Zang Yuan-Sheng 
Published: May 2022

Abstract
Purpose
Our study intended to explore how low-dose anti-angiogenic drugs affected anti-tumor immunity of tumor-infiltrating exhausted CD8+T cells and achieved better clinical response when combined with immunotherapy. We set out to find potential targets or predictive biomarker on CD8+\T cells for immunotherapy.
Methods
We tested different doses of anti-VEGFR2 antibody combined with anti-PD1 antibody to treat LUAD in vivo and analyzed tumor-infiltrating CD8+T cells by flow cytometry. CD8+T cells overexpressing LAYN were co-cultured with LA795 cell lines to identify the function of LAYN in CD8+T cells. We also analyzed clinical samples from advanced LUAD patients treated with anti-angiogenesis therapy combined with immunotherapy.
Results
Low-dose anti-VEGFR2 antibody combined with anti-PD1 antibody treatment delayed tumor growth and prolonged the survival time of tumor-bearing mice. The number of tumor-infiltrating CD8+T cells was reduced and the expression of LAYN was down-regulated in tumor-infiltrating CD8+T cells in the low-dose anti-VEGFR2 combination group. It was found that LAYN inhibited the killing function of CD8+T cells. In patients with advanced LUAD who received anti-angiogenesis therapy combined with immunotherapy, the LAYN+CD8+T cell subpopulation in good responders was significantly higher than that in poor responders. Furthermore, we demonstrated the expression of LAYN was regulated by upstream transcription factor NR4A1.
Conclusion
Low-dose anti-VEGFR2 antibody combined with anti-PD1 antibody therapy promoted anti-tumor immunity and the downregulation of LAYN in tumor-infiltrating CD8+T cells played an important role in this process. These findings had implications for improving the efficacy of immune checkpoint blockade therapy and further optimized clinical treatment guidelines in advanced LUAD.
Risk factors of proliferative diabetic retinopathy in Chinese Patients with Type 2 Diabetes
Authors: zhu lili , Wang Jianyong , Fu Xiaojin 
Published: May 2022

Abstract
Background: To investigate the relationship between systemic parameters and proliferative diabetic retinopathy(PDR) in Type 2 diabetes mellitus(T2DM).Methods: This was a cross-sectional study. Based on retinal examination findings, diabetic patients were classified into three groups: non-diabetic retinopathy (non-DR), non-proliferative diabetic retinopathy (NPDR), and PDR. The comprehensive medical data was used for analysis. Odds ratios(OR) from multinomial logistic regression models were calculated to obtain the risk factors of PDR, and a prediction model was built whose predictive ability was assessed by the area under the receiver operating characteristic curves (AUROC).Results: The study comprised 801 patients with non-DR, 330 patients with NPDR, and 99 patients with PDR. The systemic factors associated with PDR were: duration of diabetes(P < 0.000), Haemoglobin A1c (P = 0.015) , fasting plasma glucose (P = 0.001), total cholesterol(P = 0.007), estimated glomerular filtration rate (P = 0.024), and MPV(P = 0.005). The mean platelet volume (MPV) demonstrated an increasing trend with the severity of DR, whose differences were statistically significant among the three groups(P = 0.045). The prediction model which was based on multi-factors showed stronger predictive power for PDR (AUROC=0.790) than these risk factors of PDR. Conclusions: Some systemic factors including MPV are independently associated with PDR in T2DM. The prediction model might be a beneficial prognostic marker of PDR in patients with T2DM.
The Effect of Biopreservatives on the Chemical Properties of Tomato Paste and Predicting Results with Artificial Neural Networks
Authors: Mohebbi Maryam 
Published: May 2022

Abstract
This study aimed to develop a tomato paste using biopreservatives as substitutes for chemical preservatives. Fennel seed (Foeniculum vulgare Mill) (FSE) and Ziziphora clinopodioides Lam. extract (ZCE) were used as biopreservatives. Physico-chemical properties of tomato paste such as pH, titratable acidity and total soluble solid (brix) were measured during five weeks of storage at 4°C. The results showed that the incorporation of different concentrations of FSE and ZCE significantly (p < 0.05) caused to decreasing in pH and increasing in acidity of tomato pastes. Increasing the extracts level in tomato paste samples significantly (p < 0.05) resulted in increased brix during storage. Overall it can be concluded that utilization of 2 or 3% FSE as biopreservative resulted in the desirable physicochemical in tomato paste. Finally, the self-organizing map (SOM) showed that the winner neuron which has the most data is neuron 31. Input data to perceptron artificial neural network are concentration, and during different weeks (time) is considered as output. The values ​​of the correlation coefficient (R2) and the mean of squared errors (MSE) used to evaluate the perceptron artificial neural network with 1 hidden layers and 31 neurons are 0.99301 ,0.99288, 0.000016499, and 0.0085227, respectively, indicating the high accuracy of the network
Prognostic value of neutrophils to lymphocytes and platelets ratio for 28-day mortality in patients with acute respiratory distress syndrome：A retrospective study
Authors: Nie Shiyu , Wang Hongjin , Liu Qiuyu , Tang Ze , Tao Wu , Wang Nian 
Published: May 2022

Abstract
Background
Acute respiratory distress syndrome (ARDS) is a rapidly progressive and fatal respiratory failure disease that often occurs in critically ill patients. Since ARDS is associated with immune dysregulation and coagulation abnormalities, it is necessary to identify an appropriate predictor that can accurately predict ARDS mortality based on its pathophysiology. Therefore, this study aimed to evaluate the clinical value of neutrophils to lymphocytes and platelets ratio (N/LPR) in predicting 28-day mortality in ARDS patients.
Methods
From July 2018 to October 2021, the medical records of ARDS patients were retrospective reviewed. Neutrophil count, lymphocyte count, and platelet count were collected, and the neutrophil-to-lymphocyte ratio (NLR) and N/LPR were calculated. Multivariate logistic regression analyses were performed to identify independent predictors of 28-day mortality in ARDS. Receiver operating characteristic (ROC) curve with the area under curve (AUC) was used to evaluate optimal cutoff values for 28-day mortality in ARDS. Kaplan-Meier analysis was used to estimate the 28-day survival probabilities stratified by optimal cutoff values of N/LPR and NLR.
Results
A total of 136 ARDS patients were included in this study and were further divided into survivors (n = 69) and non-survivors (n = 67) groups according to their survival status after 28 days. There were no significant differences between the two groups in age, sex, history of smoking and drinking, comorbidities, and reasons of admission (P > 0.05). Non-survivors had significantly higher neutrophil counts, NLR and N/LPR and had significantly lower platelet counts than survivors (P < 0.05). Multivariate regression analysis revealed that N/LPR, NLR and platelet counts were independent predictors for 28-day mortality in ARDS (P < 0.05). The ROC analyses showed that N/LPR with optimal cutoff value of 10.57(sensitivity: 74.6%; specificity:72.5%) is a more reliable predictor for 28-day mortality in ARDS than NLR and platelet count (AUC:0.785 vs. 0.679vs. 0.326). Further subgroup analysis confirmed that ARDS patients with N/LPR < 10.57 had significantly lower 28-day mortality than patients with N/LPR ≥ 10.57(P < 0.001). Kaplan–Meier analysis also confirmed that ARDS patients with N/LPR < 10.57 had significantly longer survival.
Conclusion
N/LPR is an independent risk factor associated with 28-day mortality in ARDS patients and shows better performance in predicting mortality rate than NLR.
Altered Frontal Connectivity as a Mechanism for Executive Function Deficits in Fragile X Syndrome
Authors: Schmitt Lauren Michelle , Li Joy , Liu Rui , Horn Paul , Sweeney John A. , Erickson Craig A , Pedapati Ernest V 
Published: May 2022

Abstract
Background
Fragile X Syndrome (FXS) is the leading inherited monogenetic cause of intellectual disability and autism spectrum disorder. Executive function (EF), necessary for adaptive goal-oriented behavior and dependent on frontal lobe function, is impaired in individuals with FXS. Yet, little is known how alterations in frontal lobe neural activity is related to EF deficits in FXS.
Methods
Sixty-one participants with FXS (54% males) and 71 age- and sex-matched TDC (58% males) completed a five-minute resting state electroencephalography (EEG) protocol and a computerized battery of tests of EF, the Test of Attentional Performance for Children (KiTAP). Following source localization (minimum-norm estimate), we computed debiased-weighted phase lag index (dWPLI), a phase connectivity value, for pairings between 18 nodes in frontal regions for gamma (30–55 Hz) and alpha (10.5–12.5 Hz) bands. Linear models were generated with fixed factors of group, sex, frequency, and connection. Relationships between frontal connectivity and EF variables also were examined.
Results
Individuals with FXS demonstrated increased gamma band and reduced alpha band connectivity across all frontal regions and across hemispheres compared to TDC. After controlling for nonverbal IQ, increased error rates on EF tasks were associated with increased gamma band and reduced alpha band connectivity.
Limitations:
Frontal connectivity findings are limited to intrinsic brain activity during rest and may not generalize to frontal connectivity during EF tasks or everyday function.
Conclusions
We report gamma hyper-connectivity and alpha hypo-connectivity within source-localized frontal brain regions in FXS compared to TDC during resting-state EEG. For the first time, we report significant associations between EF and altered frontal connectivity, with increased error rate relating to increased gamma band connectivity and reduced alpha band connectivity. These findings suggest increased phase connectivity within gamma band may impair EF performance, whereas greater alpha band connectivity may provide compensatory support for EF. Together, these findings provide important insight into neurophysiological mechanisms of EF deficits in FXS, and provide novel targets for treatment development.
Rainfall maps in northeastern Mexico, a space-time interpolation approach through Kriging and Hurst exponent
Authors: Arriaga Jesús , Marin Aldo , Cantú José , Hernández Francisco , Morales Javier , González Omar , Almaguer Francisco 
Published: May 2022

Abstract
Abstract The planning and efficient use of hydrological resources is a fundamental problem in the semidesert regions of Mexico. Of the hydrological regions, the San Juan River basin, located in northeastern Mexico between the states of Coahuila, Nuevo Le´on and Tamaulipas, is of great importance for the region’s productive and agricultural activities. This work analyses 79 rainfall station records for the period between 1998 and 2018. A kriging-Hurst spatial interpolation model, which generates rainfall maps that allow the identification of areas where rainfall can best be utilized, is presented. In the analysis, the rainfall maps obtained from the spatial interpolation using the ordinary kriging technique were compared with maps generated using the kriging technique combined with the Hurst exponent. As a result of the research, evidence of a strong correlation was found between anti-persistent rainfall patterns and large average annual rainfall averages.
Quantitative Estimation of Fe-based Amorphous Coating Thickness Based on Pulsed Eddy Current Technology
Authors: Huang Xiaofei , Liu Zenghua , Gong Yu , Wu Sha , Chen Kewei , He Cunfu 
Published: May 2022

Abstract
Fe-based amorphous coatings prepared by high-velocity oxy-fuel (HVOF) spraying have the advantages of good mechanical properties, high density, low porosity, and high amorphous content. The service life and bonding strength of coating greatly depend on its thickness; however, the characterization of ferromagnetic coating thickness is a very difficult problem. Pulsed eddy current (PEC) is characterized by abundant signals in frequency domains. In this paper, the thickness measurement principle of ferromagnetic coating was explored, and the typical and entropy features from PEC signals were extracted. Seven integrated learning methods were combined to quantitatively characterize the coating thickness, namely Ridge Regression (RR), Lasso Regression (LR), Random Forest Regression (RFR), Extra Trees Regression (ETR), Gradient Boosting Tree Regression (GBTR), Addaptive Boost Regression (ABR) and eXtreme Gradient Boosting Regression (XGBR) algorithms. By comparing typical features with new ones, it was verified that the effective combination of entropy features and typical features could be used as effective feature parameters of eddy current signal. Statistical scores (RMSE and R2) and GridsearchCV features were used to evaluate and optimize the established model. As indicated by the results, the proposed XGBR machine learning model well predicted the coating thickness, and the relative error less than 0.05 mm.
Comparison of wear of interim crowns in accordance with the build angle of digital light processing 3-dimensional printing: A pilot in vivo study
Authors: Lee Hakjun , Son KeunBaDa , Lee Du-Hyeong , Kim So-Yeun , Lee Kyu-Bok 
Published: May 2022

Abstract
Background: There are still insufficient studies of the relationship between the clinical wear and build angle of the interim crowns fabricated with the DLP 3D printing. The purpose of this study was to evaluate the wear volume in the interim crown fabricated according to the printing angle of DLP 3D printing.Methods: This study included five patients who needed the single crown in the mandible molar. Interim crowns were fabricated directly in the oral cavity with the conventional method. Using a DLP 3D printer, the crowns were fabricated by setting the angles to 0, 45, and 90 degrees. Four fabricated interim crowns, using the conventional method, were randomly delivered to the patients, and used respectively for one week. The intaglio surface of interim crowns before and after use were scanned with a 3D scanner. In addition, volume changes before and after use were measured, and 3D height changes of the occlusal surface were evaluated by calculating the RMS value. Statistical analysis verified the data normality, and each group’s wear volume was evaluated, using One-way ANOVA and Tukey HSD test (α = 0.05).Results: The value was significantly higher at 90 degrees compared to the conventional method and 0 degrees (P < 0.05). There were significantly higher volume change values at 90 degrees compared to the conventional method (P < 0.05). In addition, the interim crowns fabricated with the conventional method showed the lowest changes in the RMS and volume values (P < 0.05).Conclusions: The 90 degrees printing angle is not recommended when interim crowns are fabricated with the DLP 3D printing method.Trial registration: The study protocol was approved by the Kyungpook National University Dental Hospital Institutional Review Board (approval number: KNUDH-2021-11-02-01).
KN026, a Bispecific Anti-HER2 Antibody, Combined with KN046, an Anti-CTLA-4/PD-L1 Antibody, in Patients with HER2-positive Advanced Gastrointestinal Cancer: a multicenter, open-label, nonrandomized, phase Ib study
Authors: Dong Zhi , Gong Jifang , Liu Dan , Zhang Xiaotian , Luo Suxia , Peng Zhi , Wang Yankun , Qi Changsong , Wang Zhenghang , Li Jian , Wang Xicheng , Lu Ming , Lu Zhihao , Zhou Jun , Cao Yansuo , Yuan Jiajia , Shen Lin 
Published: May 2022

Abstract
Background
Anti-HER2 antibodies combined with immune checkpoint inhibitors exert synergistic effects on innate and adaptive immunity. This phase Ib study assessed the safety and efficacy of KN026 plus KN046 in patients with HER2-positive gastrointestinal cancer.
Methods
Treatment naïve or pretreated locally advanced or metastasis, gastrointestinal cancer patients with HER2 alterations were enrolled. Four dose combinations of KN026 (20 mg/kg Q2W or 30 mg/kg Q3w) and KN046 (3 mg/kg Q2w or 5 mg/kg Q2w/Q3w) were designed. The primary objective was to assess dose-limiting toxicity (DLT) and preliminary efficacy.
Results
Overall, 47 patients were enrolled. No DLTs were observed. Any-grade treatment-related adverse events (TRAEs) were observed in 42 patients (89.4%). Anemia (40.4%), infusion-related reactions (36.2%), and elevated alanine transaminase (ALT) (27.7%) were the most common TRAEs. Grade 3 or worse TRAEs occurred in 17% of the patients. Twenty-four of the 47 patients suffered immune-related adverse events (irAEs). Rash (14.9%), hypothyroidism (6.4%) and interstitial lung disease (6.4%) were most commonly observed. Forty of 47 patients were included in efficacy assessment. The objective response rates (ORRs) in the patients with HER2-positive gastric cancer and gastroesophageal junction (GC/GEJ) adenocarcinoma in the first-line and late-line settings were 71.4% and 37.5%, respectively. No disease remission was observed in the patients with low HER2 expression or HER2 mutation. Notably, half of the patients (2/4) pretreated with trastuzumab and a programmed cell death-1 (PD-1) blockade achieved partial response (PR).
Conclusions and Relevance
: KN026 combined with KN046 exhibited acceptable safety profiles and encouraging efficacy in patients with HER2-positive gastrointestinal cancer.
Trial registration:
ClinicalTrials.gov, NCT NCT04040699, Registered August 1,2019.
Analysis of key genes and immune infiltration in ruptured intracranial aneurysms based on artificial neural networks and bioinformatics
Authors: Jia Qi , Shi Wei-Hua , Lu Xiao-Jian , Sun Shu-Qing , Shao Jun-Jie , Huang Qing-Feng 
Published: May 2022

Abstract
Background: Intracranial aneurysm (IA) is a potentially devastating cerebrovascular disease, and its rupture leads to subarachnoid hemorrhage with high mortality and disability rates. This study aimed to predict the potential biomarkers of ruptured intracranial aneurysms (RIAs) and explore the correlation between RIAs and immune infiltration through artificial neural networks and bioinformatics analysis.Method: Three RIA gene microarray data sets were obtained from the gene expression profile (GEO) database, with GSE13353 and GSE36791 as the training sets and GSE54083 as the validation set. Differentially expressed genes (DEGs) were obtained after the analysis. The Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and Metascape databases were used for functional enrichment analysis. A random forest tree was used to screen for disease signature genes, while a neural network model was built afterward. The accuracy was also confirmed in the validation set. Finally, immune cell infiltration in the unruptured IAsand RIAs groups was analyzed using CIBERSORT.Results: A total of 27 DEGs were identified by the analysis, 1 of which was a downregulated gene and 26 were upregulated genes. The functional enrichment associated with RIAs was closely related to inflammation and immune function. Hexokinase 3, matrix metalloproteinase 9, CST7, NCF2, and uridine phosphorylase 1 were disease signature genes for RIAs and could be used as potential markers for predicting RIAs. The numbers of CD8+ T cells, CD4+ memory T cells, activated natural killer cells, macrophages M0, and neutrophils were high in the RIA group in immune cell infiltration analysis.Conclusion: The analysis revealed disease signature genes and immune cell infiltration types that predicted RIAs and had important effects on inflammatory and immune responses.
Dorsal raphe serotonergic neurons mediate depression in a mouse model of loss of control over stress
Authors: Yongfeng li , Yao Li , Zheng Qiaohua , Qian Zhaoqiang , Li Ningrao , Wei Chunling , Han Jing , Liu Zhiqiang , Ren Wei , Qiao Haifa 
Published: May 2022

Abstract
Our previous study found that, in a triadic experiment, helplessness exhibited in mice in the loss of control over stress (LOC) group in response to aversive events was more prominent than that seen in the yoked (Yoked) group of mice. However, the mechanisms responsible for such phenomena are poorly understood. Increasing evidence has demonstrated that 5-hydroxytryptamine (5-HT) plays a critical role in emotional behaviours. Therefore, we hypothesized that the serotonergic system might mediate depression induced by the loss of control over stress. Our results showed that the activity level of 5-HT neurons of mice in the LOC group was significantly higher than that of mice in the Yoked and Control groups. Additionally, optogenetic inhibition of 5-HT neuron projections from the dorsal raphe nucleus (DRN) to the ventral hippocampus (VH) significantly reduced escape latency and freezing time, improved escape defect behaviour of mice in the LOC/Yoked group, and downregulated the expression of DRN 5-HT1A autoreceptor (DRN 5-HT1AR) of mice in the LOC group. These results provide compelling evidence that the sensitization of dorsal raphe 5-HT neurons mediates depression in a mouse model of loss of control over stress.
Clinicopathological Characteristics of Low to Intermediate Grade Neuroendocrine Tumors with Oncocytic Features
Authors: Cui Shengjie , Liu Bella L , Mijares Kevin , Han Jing , Paulsen John D , Sun Jihong 
Published: May 2022

Abstract
Neuroendocrine tumors (NETs) with oncocytic features are rare. To date, few studies have described the metastatic characteristics of these tumors, most of which were limited by the low number of cases. One article characterized intermediate to high grade (G2 and G3) oncocytic NETs of the pancreas as having an ominous outcome; however, metastatic features of low grade oncocytic NETs have, to our knowledge, been hitherto unexplored. Our study characterized the clinicopathological and metastatic features of 32 low to intermediate grade oncocytic NETs of various organs. The most frequent metastatic site was the liver (63%). Metastatic rate of our cases was compared with Riihimaki’s study (metastatic rate of G1/G2 NETs was reported), as well as Heetfeld’s study and Lithgow’s study (metastatic rate of G3 NETs was reported). The overall metastatic rate of our cases is 84.4%, which is significantly higher than that of the G1/2 NETs from Riihimaki’s study (84.4% vs 25%, p < 0.0001), while similar to that of the G3 NETs from Heetfeld’s study (84.4% vs 86.5%, p>0.05) and Lithgow’s study (84.4% vs 80.8%, p>0.05). These data indicate that oncocytic features could potentially be characterized as a high risk feature in addition to high Ki-67 index, mitotic count and necrosis. Thus, imaging studies such as liver magnetic resonance imaging may be warranted to detect liver metastases in NETs with distinctive oncocytic cytologic features even in the absence of other high risk features.