bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enrollment of Older Metastatic Breast Cancer Patients in First Line Clinical Trials: 9-Year Experience of the Large-Scale Real-Life Multicenter French ESME Cohort
Authors: Bringuier Michael , Carton Matthieu , Levy christelle , Patsouris Anne , Pasquier David , Debled Marc , Rigal Olivier , Jacot William , Goncalves Anthony , Desmoulins Isabelle , Rouge Thibault De La Motte , Bachelot Thomas , Ferrero Jean-Marc , Eymard Jean-Christophe , Ung Mony , Mouret-reynier Marie-ange , Petit Thierry , Chevrot Michaël , Uwer Lionel , Courtinard Coralie , Frenel Jean-Sebastien , Viansone Alessandro , Baldini Capucine 
Published: June 2021

Abstract
Purpose: Older cancer patients are underrepresented in clinical trials. We aimed to understand barriers to clinical trial recruitment in women aged 70 years old (yo) or over with metastatic breast cancer (MBC).Methods: We used the national Epidemio-Strategy and Medical Economics MBC Data Platform, a French multi-center real life database. We selected MBC women over 70yo, without central nervous system metastases, with at least one line of systemic treatment, between January 1st, 2008 and December 31st, 2016, and had no other cancer in the 5 years before MBC. The primary objective was to evaluate the proportion of patients enrolled in clinical trials according to their age. Secondary objective was to identify variables associated with enrollment.Results: 5552 women were aged ≥ 70 (median 74yo; IQR72-77). 14611 were less than 70. Of the older ones, 239 (4%) were enrolled in a clinical trial during first line of treatment, compared with 1529 (10.5%) for younger ones. Multivariable analysis of variables predicting for enrollment during first line of treatment in older patients were younger age (OR 0.50 [95%CI; 0.33-0.76] for the 80-85yo class; OR 0.17 [95%CI; 0.06-0.39] for the 85yo and more class), good ECOG Performance Status (PS 0-1) (OR 0.15 [95%CI; 0.08-0.27] for the PS 2-4 class), HER2+ disease (OR 1.78 [95%CI; 1.27-2.48]), type of treatment (chemotherapy/targeted therapy/immunotherapy OR 5.01 [95%CI; 3.13-8.18]), and period (OR 1.65 [95%CI; 1.22–2.26] for 2012-2016, compared to 2008-2011).Conclusions: In this large database, few older MBC patients were enrolled in a trial compared with younger ones.
Transcriptomic Analysis Identified two Subtypes of Brain Tumor Characterized by Distinct Immune Infiltration and Prognosis
Authors: Shen Xilin , Shen Hongru , Feng Mengyao , Wu Dan , Yang Yichen , Li Yang , Yang Meng , Ji Wei , Wang Wei , Zhang Qiang , Song Fangfang , Liu Ben , Chen Kexin , Li Xiangchun 
Published: June 2021

Abstract
Background Brain tumor ranks the most devastating cancer type. The complex tumor immune microenvironment prevents brain tumor from therapeutic benefits. The purpose of this study was to stratify brain tumors based on their distinct immune infiltration signatures to facilitate better clinical decision making and prognosis prediction.Methods We developed a deep learning model to characterize immune infiltration from transcriptome. The developed model was applied to distill expression signatures of transcriptome of brain tumor samples. We performed molecular subtyping with the extracted expression signatures to unveil brain tumor subtypes. Computational methods including gene set enrichment analysis, Kaplan-Meier survival and multivariate Cox regression analyses were employed.Results We identified two distinctive subtypes (i.e. C1/2) of brain tumor featured by distinct immune infiltration signatures. The C1 subtype is characterized by protective immune infiltration signatures, including high infiltration of CD8+ T cells and activation of CX3CL1. The C2 subtype has an extensive infiltration of tumor-associated macrophages and microglia, and was enriched with immune suppressive, wound healing and angiogenic signatures. The C1 subtype had significantly better prognosis as compared with C2 (Log-rank test, HR: 2.5, 95% CI: 2.2 – 2.7; P = 8.2e-78). This difference remained statistically significant (multivariate Cox model, HR: 2.2, 95% CI: 1.7 – 2.9; P = 3.7e-10) by taking into account age, gender, recurrent/secondary status at sampling time, tumor grade, histology, radio-chemotherapy, IDH mutation, MGMT methylation and co-deletion of 1p and 19q. This finding was validated in 6 datasets. The C2 subtype of glioblastoma patients with IDH mutation has poor survival analogous to those without IDH mutation (Log-rank test, adjusted P = 0.8), while C1 has favorable prognosis as compared with glioblastoma of C2 subtype with IDH mutation (Log-rank test, adjusted P = 1.2e-3) or without IDH mutation (Log-rank test, adjusted P = 1.3e-6).Conclusions We identified two distinctive subtypes of brain tumor with different immune infiltration signatures and prognosis. Our finding is helpful for better understanding of brain tumor and has potential clinical utilities.
Muricauda Chongwuensis Sp. Nov., Isolated From Coastal Seawater of China
Authors: Chen Ming-Xia , He Xiao-Yu , Li He-Yang 
Published: June 2021

Abstract
In the course of screening for bacterial predator, a Gram-negative, non-flagellated, gliding, long rod-shaped and yellow-pigmented bacterium, designated strain HICWT, was isolated from coastal seawater of China. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain HICWT represented a member of the genus Muricauda and showed the highest sequence similarity to M. aquimarina JCM11811T (98.8%) and M. ruestringensis DSM13258T (98.1%). NaCl was required for growth. Optimum growth occurred at 25–30 oC, 2.0–3.0% (w/v) NaCl with pH 7.0. Strain HICWT showed some similar characteristics to the nonobligate bactertal predators, the cells can attach the prey cells. Strain HICWT contained MK-6 as the predominant respiratory quinone and had iso-C15:0, iso-C15:1 G and iso-C17:0 3-OH as the major cellular fatty acids. The polar lipids contained phosphatidylethanolamine (PE), three unknown phospholipids (PL1–PL3), one unknown aminolipids (AL) and three unknown polar lipids (L1–L3). The genome size of strain HICWT was approximately 3.8 Mbp, with a G+C content of 41.4%. On the basis of the polyphasic evidence, strain HICWT is proposed as representing a new species of the genus Muricauda, for which the name Muricauda chongwuensis sp. nov. is proposed. The type strain is HICWT (=JCM 33643T=MCCC 1K03769T).
Optimizing thermocouple’s ZT through design innovation
Authors: Zhang Tinggang 
Published: June 2021

Abstract
In this work, we demonstrate that in parallel with the one existed at high doping concentration, there also exists an optimal combination of the transport properties of a thermoelectric material at low doping concentration as the curve of the relationship between electrical conductivity and doping concentration is rigidly shifted toward lower doping concentration without disturbing the Seebeck coefficient and the thermal conductivity. Based on this finding, a new concept for thermocouple design is developed to improve the thermocouple’s efficiency and power output. The analytical model developed for the new thermocouple indicated that its efficiency and power output can be more than tripled as compared to those of the original design. A single thermocouple made of Silicon semiconductors was simulated numerically using different sets of input parameters. The results showed that the new thermocouple’s efficiency and power output can be improved significantly.
Hydrogel-Hydroxyapatite-Monomeric Collagen Type-I Scaffold with Low-Frequency Electromagnetic field Treatment Enhances Osteochondral Repair in Rabbits
Authors: Yan Jiyuan , Liu Chaoxu , Zhang Yingchi , Tu Chang , Zhang Ruizhuo , Tang Xiangyu , Li Hao , Wang Huaixi , Ma Yongzhuang , Wu Hua , Sheng Gaohong 
Published: June 2021

Abstract
Background: Cartilage damage is a common medical issue in clinical practice. Complete cartilage repair remains a significant challenge owing to the inferior quality of regenerative tissue. Methods: In this study, a composite scaffold made of Hydroxyapatite-Collagen type-I (HAC) and PLGA-PEG-PLGA thermogel was produced to match the cartilage and subchondral layers in osteochondral defects, respectively. Bone marrow mesenchymal stem cells (BMSC) encapsulated in the thermogel were stimulated by an electromagnetic field (EMF). Results: The scaffold was evaluated in rabbits, and biological characteristic of BMSCs were measured. Results showed that the scaffold with EMF enhances the repair of osteochondral defects in rabbits, and, in particular, cartilage repair. EMF could promote proliferation and chondrogenic differentiation of BMSCs partly by activating the PI3K/AKT/mTOR and Wnt1/LRP6/β-catenin pathway. Conclusion: Hydrogel-Hydroxyapatite-Monomeric Collagen type-I scaffold with low-frequency EMF treatment has the potential to enhance osteochondral repair.
Combined Lubrication of Surface Texturing and Copper Covering for Broaching Tool
Authors: Jing NI , Feng Kai , Kai Zhuang , Zhiqian Sang , Zhen Meng , Rahman Md Mizanur 
Published: June 2021

Abstract
The broaching tool is an efficient and precisely heavy-loaded metal-cutting tool, widely used in the mass production of key components related to the aerospace and automobile industries. However, the heavy load, intense squeezing, and friction in the tool-chip contact area prevent the cutting fluid from entering the desired location. Consequently, insufficient lubrication gives rise to a high-temperature built-up edge, thereby lowering machining accuracy and efficiency. To reduce frictional force, three textures (i.e., micro-pit, stripe, mesh) are prepared on the rake face of broaching tool with laser processing technique. Afterward, textured grooves are covered with copper using the reciprocating rotational friction; this artifact enhances the system’s wettability and heat dissipation ability. Experiments approve that compared to the non-textured cutting teeth, the cutting force with the stripe-textured teeth is reduced by 7.6%. Nevertheless, the cutting force is decreased by 14.6% after covering the tool surface with copper. Obtained results indicate that the wettability of cutting fluid on the surface is improved. In addition, convex peaks on the tool surface are passivated during the reciprocating rotation of the copper bar.
Bioinformatics Prediction and Experimental Verification Identify MAD2L1 and CCNB2 as Diagnostic Biomarkers of Rhabdomyosarcoma
Authors: Xia Tian , Meng Lian , Zhao Zhijuan , Li Yujun , Wen Hao , Sun Hao , Zhang Tiantian , Wei Jingxian , Li Feng , Liu Chunxia 
Published: June 2021

Abstract
Background: Rhabdomyosarcoma (RMS) is a malignant soft-tissue tumour. In recent years, the tumour microenvironment (TME) has been reported to be associated with the development of tumours. However, the relationship between the occurrence and development of RMS and TME is unclear. The purpose of this study is to identify potential tumor microenvironment-related biomarkers in rhabdomyosarcoma and analyze their molecular mechanisms, diagnostic and prognostic significance.Methods: We first applied bioinformatics method to analyse the tumour samples of 187 patients with rhabdomyosarcoma (RMS) from the Gene Expression Omnibus database (GEO). Then, we used cell function and molecular biology techniques to study the progress of RMS.Results: Bioinformatics results show that the RMS TME key genes were screened, and a TME-related tumour clinical staging model was constructed. The top 10 hub genes were screened through the establishment of a protein-protein interaction network, and then Gene Expression Profiling Interactive Analysis was conducted to measure the overall survival (OS) of the 10 hub genes in the sarcoma cases in The Cancer Genome Atlas (TCGA). Six differential genes of statistical significance were acquired. The correlation between these six differential genes and the clinical stage of RMS was analysed. Our data found that the expression levels of MAD2L1 and CCNB2 negatively correlated with the OS of RMS patients and positively correlated with the clinical stage of RMS patients. Immunohistochemical results also confirmed that the expression levels of MAD2L1 (30/33, 87.5%) and CCNB2 (33/33, 100%) were remarkably higher in RMS group than in normal control group (0/11, 0%). Moreover, the expression of CCNB2 was related to tumour size. Further gene set enrichment analysis revealed that the genes in MAD2L1 and CCNB2 groups with high expression were mainly related to the mechanism of tumour metastasis and recurrence. In the low-expression MAD2L1 and CCNB2 groups, the genes were enriched in the metabolic and immune pathways. Downregulation of MAD2L1 and CCNB2 suppressed the growth, invasion, migration, and cell cycling of RMS cells and promoted their apoptosis. The CIBERSORT immune cell fraction analysis indicated that the expression levels of MAD2L1 and CCNB2 affected the immune status in the TME. Conclusions: The expression levels of MAD2L1 and CCNB2 may help guide the prognosis of patients with RMS and the clinical staging of tumours.
A Study on the Effect of Traditional Chinese medicine Chaihu-guizhi Decoction Reducing the Susceptibility and Severity of Influenza in Depressed Mice
Authors: Hui Sun Qi , Zhao Jingye , Yang Jinghua , Zhang Xiaochen , Zheng Qingge , Zhao Shaozhe , Liu Xiaoyun , Rong Rong , Yang Yong 
Published: June 2021

Abstract
Background: Depression is one of the most common illnesses in the world. In the flu season, depressed patients are more prone to influenza infection. It causes serious health problem worldwide. Chaihu-guizhi decoction (CGD) is a classic prescription to treat depressed patients with fever in clinical practice in China. However, the pharmacological activity and mechanisms of CGD against this disease have never been reported before. We investigated the changes of depressed condition, antiviral effects, anti-inflammatory, genes and protein expressions of T-helper cell type 1/type 2 (Th1/Th2) cytokines with CGD in combined mice model. This work will provide reliable evidence of the experiments for its better clinical practice. Methods: Depressed mice were dealt with by intraperitoneal injection of reserpine solution, then intranasal infection influenza A (H1N1) virus to create combined mice model. Oral administration of CGD was conducted in mice with 30.55-61.1 g/kg/d lasting up to 6 days. Physiological indicators, behavior changes, histopathological manifestations, digestive abilities, dopamine levels and virus expressions^ of the mice were detected. Moreover, levels of Th1/Th2 cytokines, including IL-2, IL-6, IL-10, IFN-γ and TNF-α, were detected in the sera of mice. Results: The extraction of CGD at dosages of 30.55-61.1 g/kg could effectively relieve the state of depression, decrease influenza virus genes expression, reduce viscera index of the lung, ameliorate lung edema and inflammation. Administration of CGD significantly down-regulated the expression of IL-6, TNF-α and IFN-γ. CGD also manifested a decreasing trend in the ratio of IFN-γ/IL-10, compared with that of model treatment groups. Conclusion: The results reveal that the CGD could treat depression syndrome in mice combined with influenza A (H1N1) virus infection by reducing inflammation and ameliorating depressive status.
Vandetanib Drives Growth Arrest and Promotes Sensitivity to Imatinib in Hematologic Malignancies by Targeting Ephrin Type-B Receptor 4
Authors: Ma Weina , Zhu Man , Wang Bo , Gong Zhengyan , Du Xia , Yang Tianfeng , Shi Xianpeng , Dai Bingling , Zhan Yingzhuan , Zhang Dongdong , Ji Yanhong , Wang Yang , Li Song , Zhang Yanmin 
Published: June 2021

Abstract
Background: The oncogenic role of ephrin type-B receptor 4 (EphB4) has been reported in many types of tumors. However, little is known about its role in chronic myeloid leukemia (CML). Methods: A pool of clinically approved tyrosine kinase inhibitors (TKI) were screened for the antitumor activity using various hematologic cancer cell lines with different levels of EphB4 expression. To investigate whether EphB4 serves as a major therapeutic target in vandetanib-mediated inhibition on CML, the binding affinity of vandetanib to the active sites of extracellular and intracellular domains of EphB4 was evaluated using affinity chromatography and surface plasmon resonance. The binding regions were defined by molecular dynamics simulations and CRISPR/Cas9. Furthermore, the anticancer activity of vandetanib was evaluated by in vitro MTT assay and in vivo therapeutic study.Results: Here, Gene Expression Omnibus (GEO) data and blood analyses of CML patients revealed higher levels of EphB4 expression in CML patients than in healthy subjects. EphB4 knockdown inhibited K562 cell growth in vitro. In addition, transient transfection of EphB4 siRNA led to sensitization to imatinib. These growth defects could be fully rescued by EphB4 transfection. To develop an anti-EphB4 therapy with rapid clinical translation for CML, vandetanib from a pool of clinically approved TKIs were screened. Vandetanib mainly acts on the intracellular tyrosine kinase domain and interacts stably with a hydrophobic pocket. Furthermore, vandetanib downregulated EphB4 protein level via ubiquitin-proteasome pathway and inhibited the signaling pathways of PI3K/AKT and MAPK/ERK in K562 cells. Vandetanib alone led to significant inhibition of tumor growth in a K562 xenograft model. More importantly, combination of vandetanib and imatinib exhibited enhanced and synergistic growth inhibition against imatinib-resistant K562 cells in vitro and in vivo. Conclusions: These findings suggest that vandetanib drives growth arrest and overcomes the resistance to imatinib in CML via targeting EphB4.
Design, Implementation and Initial Findings of COVID-19 Research in the Rotterdam Study: Leveraging Existing Infrastructure for Population-Based Investigations on An Emerging Disease
Authors: Licher Silvan , Terzikhan Natalie , Splinter Marije J. , Velek Premysl , Rooij Frank J.A. Van , Heemst Jolande Verkroost-van , Haarman Annechien E.G. , Thee Eric F. , Geurts Sven , Mens Michelle M.J. , Schaft Niels van der , de Feijter Maud , Pardo Luba M. , Kieboom Brenda C.T. , Ikram M. Arfan 
Published: June 2021

Abstract
The Rotterdam Study is an ongoing prospective, population-based cohort study that started in 1989 in the city of Rotterdam, the Netherlands. The study aims to unravel etiology, preclinical course, natural history and potential targets for intervention for chronic diseases in mid-life and late-life. It focuses on cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, otolaryngological, locomotor, and respiratory diseases. In response to the COVID-19 pandemic, a substudy was designed and embedded within the Rotterdam Study. On the 20th of April, 2020, all living non-institutionalized participants of the Rotterdam Study (n = 8,732) were invited to participate in this sub-study by filling out a series of questionnaires administered over a period of eight months. These questionnaires included questions on COVID-19 related symptoms and risk factors, characterization of lifestyle and mental health changes, and determination of health care seeking and health care avoiding behavior during the pandemic. As of May 2021, the questionnaire had been sent out repeatedly for a total of six times with an overall response rate of 76%. This article provides an overview of the rationale, design, and implementation of this sub-study nested within the Rotterdam Study. Finally, initial results on participant characteristics and prevalence of COVID-19 in this community-dwelling population are shown.
Longitudinal association between ambient nitrogen dioxide exposure and all-cause mortality in Chinese adults
Authors: Zhang Yunquan , Wei Jing , Zhan Yu , Yang Zhiming , Liu Riyang , Zhang Yuanyuan , Liu Linjiong , Ma Zongwei 
Published: June 2021

Abstract
A number of population-based studies have investigated long-term effects of nitrogen dioxide (NO2) on mortality, while great heterogeneities exist between studies. In highly populated countries in Asia, cohort evidence for NO2-mortality association was extensively sparse. This study aimed to quantify longitudinal association of ambient NO2 exposure with all-cause mortality in Chinese adults. A national cohort of 30,843 adult men and women were drawn from 25 provincial regions across mainland China, and followed up from 2010 through 2018. Participants’ exposures to ambient air pollutants were assigned according to their residential counties at baseline, through deriving monthly estimates from high-quality gridded datasets developed by machine learning methods. Cox proportional hazards models with time-varying exposures were utilized to assess the association of all-cause mortality with long-term exposure to ambient NO2. An approximately linear NO2-mortality relation (p=0.273 for nonlinearity) was identified across a broad exposure range of 6.9–57.4 μg/m3. Per 10-µg/m3 increase in annual NO2 exposure was associated with an hazard ratio of 1.127 (95% confidence interval: 1.042–1.219, p<0.003) for all-cause mortality. Risk estimates remained robust after additionally adjusting for the confounding effects of co-pollutants (i.e., PM2.5 or O3). In 2018, 1.65 million deaths could be attributed to ambient NO2 exposure (national average 17.3 µg/m3) in China, representing a decrease of 4.3% compared with the estimate of 1.72 million in 2010 (20.5 µg/m3). This cohort study provided national evidence for elevated risk of all-cause mortality associated with long-term exposure to ambient NO2 in Chinese adults.
Spatial Positional Relationship Between Macular Superficial Vessel Density and Ganglion Cell-Inner Plexiform Layer Thickness in Primary Angle Closure Glaucoma
Authors: Lin Yongdong , Ma Di , Wang Hongxi , Chen Shirong , Zhang Mingzhi 
Published: June 2021

Abstract
Purpose: To evaluate the spatial relationship between macular superficial vessel density (SVD) and macular ganglion cell-inner plexiform layer (GCIPL) thickness in primary angle-closure glaucoma (PACG), and to investigate diagnostic abilities of macular SVD and foveal avascular zone (FAZ) parameters.Methods: This was a cross-sectional study on 38 PACG patients (38 eyes) and 25 healthy subjects (25 eyes). Macular region was imaged using a 1050-nm-wavelength swept-source optical coherence tomography (OCT) angiography (OCTA) system (DRI OCT Triton, TOPCON). Vessel density of the macular region was quantified by ImageJ software. The peripapillary retinal nerve fiber layer (pRNFL) thicknesses and macular GCIPL thickness were obtained by swept-source OCT. Pearson correlation analysis was used to evaluate the spatial positional relationship between macular SVD and macular GCIPL thickness. At the same time, the correlation between macular SVD and pRNFL thickness was evaluated. Areas under the receiver operating characteristics curves (AUCs) of OCT, OCTA and FAZ measurement metrics were calculated to assess the diagnostic ability for glaucoma.Results: Macular GCIPL thickness had a moderate correlation with the macular SVD in the inferonasal sector (r = 0.426, P = 0.008). In addition, there was a strong correlation between inferonasal sector of macular vessel density and 5,6,7,8 clock-hour regions of the pRNFL thicknesses(all r>0.5). Inferoinferior sector of macular SVD and 6,7 clock-hour regions of pRNFL thicknesses also had strong correlation (all r>0.5).The AUCs of macular SVD ranged between 0.61 (superonasal sector) and 0.76 (inferoinferior sector).The FAZ circularity index showed the highest diagnostic power (AUC= 0.94;95% CI, 0.85-0.99), followed by superotemporal sector of macular GCIPL thicknesses (0.93;95% CI,0.83-0.98).Conclusions: Sector of macular SVD not only had a spatial positional correlation with corresponding macular GCIPL thickness, but also with clock-hour regional pRNFL thicknesses in PACG eyes. FAZ circulation index might be a useful diagnostic parameter.