bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alterations of White Matter Integrity in Cerebral Small Vessel Disease and Their Correlation with Cognitive Performance: A Trace-Based Spatial Statistics Study
Authors: Wang Yifan , Wang Tianyao , Yu Zekuan , Huang Bo , Liu Biao , Liu Xianwei , Yin Huabin , Liu Jun 
Published: January 2021

Abstract
Background: This study aimed to understand the injury of white matter (WM) microstructure behind white matter hyperintensities (WMH) and identify the regions where injury was more pronounced with increasing WMH severity. Moreover, we analyzed whether this microstructural injury is related to cognition. Methods: 110 patients with WMH were recruited in this research. All subjects underwent 3.0T MRI scans and neuropsychological cognitive assessments. Simple mental state examination (MMSE) along with Montreal Cognitive Assessment (MoCA) were applied to assess the patient's overall cognitive ability. WMH of each subject was graded according to Fazekas grade scale and was divided into two groups: (A) WMH score of 1-2 points (n=64), (b) WMH score of 3-6 points (n=46). Trace-based spatial statistics (TBSS) was applied for the analysis of diffusion tensor imaging (DTI) data. All statistical analyses were performed in SPSS 26.0 statistical software. Results: The results indicate that patients with higher WMH scores showed extensively symmetrical areas of increased mean diffusion, axial diffusion and radial diffusion involving bilateral anterior limb, posterior limb and retrolenticular part of internal capsule, posterior corona radiata, external capsule, superior longitudinal fasciculus, and superior fronto-occipital fasciculus (P < 0.01). Conclusions: Finally, we come to the conclusion that cognition-related WM fiber tracts tend to be more vulnerable to be injured in patients of cerebral small vessel disease (CSVD). Moreover, changes in WM microstructure often predate changes of cognition. Early detection of microstructural changes and timely intervention can delay cognitive decline to some extent.
Risk Factors for Ectopic Pregnancy: A Multi-center Case Control Study
Authors: Atta Nooria , Aram Fahima , Naseri Nafisa , Sahak Mahbooba 
Published: January 2021

Abstract
Background: Ectopic pregnancy (EP) is defined as a pregnancy in which fertilized oocyte implants outside the endometrial cavity. Although there is no known etiology for ectopic pregnancy, some risk factors of EP have been determined. It has been evident that ectopic pregnancy can be of multifactorial origin. This multicenter research aims to study risk factors associated with increased risk of ectopic pregnancy in women living in Kabul. Methods: A multicenter case control study was conducted in five tertiary maternity hospitals located in Kabul, Afghanistan. A total of 457 pregnant women were included in this study. In the case group, women with diagnosed ectopic pregnancy, while in control group women with intrauterine pregnancy were included. For each case in this study, two controls were enrolled. Results: The mean (SD) age of women in case group was 27.9 (6) years while in control group it was 26.4 (5.5) years. This difference was not statistically significant. We found a significant association between history of abortion and EP (Adj. OR=1.57; 95%CI: 1.02, 2.42). Having history of abdominal/pelvic surgery was a risk factor for EP with adjusted OR 1.94 (95%CI: 1.15, 3.30). In this study we found an increasing risk of EP in women of 35 years or older compared to younger women (Crude OR=2.26; p= 0.024). In women reporting prior EP, the chance of its recurrence was increased (Crude OR= 9.64; 95%CI: 1.1, 83.2). No association of gravidity and parity was found with EP incidence. Conclusions: In this study we found a statistically significant association between history of abdominal/pelvic surgery and EP. In addition, history of abortion was suggested as a risk factor for ectopic pregnancy. In case of having a previous EP probability of its recurrence will be increased. Women with advanced age having other potential risk factors will be facing higher risk of EP.
Superlinear scaling of riverine biogeochemical function with watershed size
Authors: Wollheim Wilfred , Harms Tamara , Robison Andrew , Koenig Lauren , Helton Ashley , Song Chao , Bowden William , Finlay Jacques 
Published: January 2021

Abstract
River networks are a crucial component of the earth system because they regulate carbon and nutrient exchange between continents, the atmosphere, and oceans. Quantifying the role of river networks at broad spatial scales must accommodate spatial heterogeneity, discharge variability, and upstream-downstream connectivity. Allometric scaling relationships of cumulative biogeochemical function with watershed size integrate these factors, providing an approach for understanding the role of fluvial networks in the earth system. Here we demonstrate that allometric scaling relationships of cumulative river network function are linear (power exponent ~ 1) when biogeochemical reactivity is high and river discharges are low, but become increasingly superlinear (power exponent > 1) as reactivity declines or discharge increases. Superlinear scaling indicates that biogeochemical function of entire river networks within a watershed is an emergent property that increases disproportionately with increasing watershed size. Expanding observation networks will increase precision in riverine fluxes of carbon and nutrients estimated by allometric scaling functions.
Starfish-inspired Ultrasound Ciliary Bands for Microrobotic Systems
Authors: Dillinger Cornel , Nama Nitesh , Ahmed Daniel 
Published: January 2021

Abstract
Cilia are short, hair-like appendages ubiquitous in various biological systems, which have evolved to manipulate and gather food in liquids at regimes where viscosity dominates inertia. Inspired by these natural systems, synthetic cilia have been developed and cleverly utilized in microfluidics and microrobotics to achieve functionalities such as propulsion, liquid pumping and mixing, and particle manipulation. In this article, we present the first demonstration of ultrasound-activated synthetic ciliary bands that mimic the natural arrangements of ciliary bands on the surface of starfish larva. Our system leverages nonlinear acoustics at microscales to drive bulk fluid motion via acoustically actuated small-amplitude oscillations of synthetic cilia. By arranging the planar ciliary bands angled towards (+) or away (–) from each other, we achieve bulk fluid motion akin to a flow source or sink. We further combine these flow characteristics with a novel physical principle to circumvent the scallop theorem and realize acoustic-based propulsion at microscales. Finally, inspired by the feeding mechanism of a starfish larva, we demonstrate an analogous microparticle trap by arranging + and – ciliary bands adjacent to each other.
Evaluation of the Expression Levels of Cannabinoid Type-1 (CB1) Receptor and Phosphorylated Extracellular Signal-Regulated Kinase (p-ERK) in Gliomas
Authors: Choucair Nader , Sakr Zahraa , Eddine Hassane Kheir , Zaarour Mariana , Harati Hayat , Fares Youssef , Bahmad Hisham , Nabha Sanaa 
Published: January 2021

Abstract
Background

Gliomas are the most frequent primary brain tumors and one of the most aggressive forms of cancer. Recently, numerous studies have focused on cannabinoids as a new cancer-therapeutic approach due to their antineoplastic effects through activation of the cannabinoid receptors, CB1 and CB2. The aim of this study was to investigate the expression levels of cannabinoid type-1 (CB1) receptors and phosphorylated extracellular signal-regulated kinase (p-ERK) in human glioma samples and evaluate their clinicopathologic significance.
Materials and Methods

We analyzed the expressions of CB1 receptors (CB1R) and p-ERK in 61 paraffin-embedded gliomas and 4 normal brain tissues using automated immunohistochemical assay. CB1R and p-ERK expressions were categorized into high versus low expression levels. Statistical analyses were performed to evaluate the association between CB1R and p-ERK expression levels and the clinicopathologic features and overall survival.
Results

Our results showed that CB1R is down-expressed in glioma tissues compared to normal brain tissues. However, the low expression of CB1R was found to be not related to the malignancy grade of gliomas. Conversely, higher expression of p-ERK was noted in gliomas compared to normal brain tissues, with no association observed with tumor grades. In addition, CB1R expression was not observed to be associated with clinicopathologic features of gliomas, except for p-ERK expression.
Conclusion

Our findings indicate a down-expression of CB1R and overexpression of p-ERK in glioma tissues when compared to non-cancerous brain tissues. This change in CB1R expression in gliomas may contribute to further research on the therapeutic effects of cannabinoids in human gliomas.
Alkaline Phosphatase Downregulation Promotes Lung Adenocarcinoma Metastasis via the C-Myc/RhoA&nbsp;Axis
Authors: Lou Zhefeng , Lin Weiwei , Zhao Huirong , Jiao Xueli , Wang Cong , Zhao He , Liu Lu , Liu Yu , Xie Qipeng , Huang Xing , Huang Haishan , Zhao Lingling 
Published: January 2021

Abstract
Background: Lung adenocarcinoma (LUAD) metastasis significantly reduces patient survival; hence inhibiting the metastatic ability of lung cancer cells will greatly prolong patient survival. Alkaline phosphatase (ALPL), a homodimeric cell surface phosphohydrolase, is reported to play a controversial role in prostate cancer and ovarian cancer cell migration; however, the function of ALPL in LUAD and the related mechanisms remain unclear.Methods: TCGA database was used to analysis the expression of ALPL, and further verification was performed in a cohort of 36 LUAD samples by qPCR and western blot. Soft-agar assay, transwell assay and lung metastasis assay were employed to detect the function of ALPL in LUAD progression. The qPCR, luciferase promoter reporter assay and western blot were used to clarify the molecular mechanisms of ALPL in promoting metastasis in LUAD.Results: ALPL was downregulated in LUAD, and the disease-free survival rate of patients with low ALPL was significantly reduced. Further studies showed that overexpression of ALPL in LUAD cell lines did not significantly affect cell proliferation, but it did significantly attenuate lung metastasis in a mouse model. ALPL downregulation in LUAD led to a decrease in the amount of phosphorylated (p)-ERK. Because p-ERK promotes the classical c-Myc degradation pathway, the decrease in p-ERK led to the accumulation of c-Myc and therefore to an increase in RhoA transcription, which enhanced LUAD cell metastasis.Conclusion: ALPL specially inhibits the metastasis of LUAD cells by affecting the p-ERK/c-Myc/RhoA axis, providing a theoretical basis for the targeted therapy of clinical LUAD.
The CAFs&nbsp;Related Gene CALD1&nbsp;Is a Prognostic Biomarker and Correlated With Immune Infiltration in Bladder Cancer
Authors: Du YiHeng , Jiang Xiang , Wang Bo , Cao Jin , Wang Yi , Yu Jiang , Wang XiZhi , Liu HaiTao 
Published: January 2021

Abstract
Background: Stromal components of the tumor microenvironment contribute to bladder cancer progression, and Cancer-Associated Fibroblasts (CAFs) were reported to play an important role. Accumulating pieces of evidence indicate that CAFs participate in the crosstalk with tumor cells and have a complex interaction network with immune components. Further study of the role of CAFs in the bladder cancer microenvironment and the search for possible specific markers are important for a deeper understanding of the roles of CAFs in bladder cancer progression and immunomodulation.Methods: In the present study, we examined the abundance of CAFs in the TCGA and GEO datasets using the MCP-Counter algorithm. Additionally, the expression of genes related to CAFs was analyzed through the Weighted Gene Co-expression Network Analysis (WGCNA). The CIBERSORT and ESTIMATE algorithms were used for the correlation analysis between the key CAFs related gene and the tumor microenvironment components.Immunohistochemistry analysis in clinical samples was used to validate the results of bioinformatics analysis.Results: The results showed that CAFs were closely associated with the progression and prognosis of bladder cancer. WGCNA also revealed that CALD1 was a key gene significantly associated with CAFs in bladder cancer. Moreover, the further in-depth analysis showed that CALD1 significantly affected the progression and prognosis of bladder cancer. The CIBERSORT and ESTIMATE algorithms significant correlations between CALD1 and the tumor microenvironment components, including CAFs, macrophages, T cells, and multiple immune checkpoint related genes. Finally, immunohistochemistry results of clinical samples' validated the strong association between CALD1, CAFs, and macrophages.Conclusions: In the present study, we confirmed the cancer-promoting roles of CAFs in bladder cancer. Being a key gene associated with CAFs, CALD1 may promote bladder cancer progression by remodeling the tumor microenvironment. The bioinformatics methods, including the CIBERSORT, MCP-COUNTER and ESTIMATE algorithms, may provide important value for studying the tumor microenvironment.
LAMC1, Upregulated by TGFβ in Tumor Cells, Contributed to The Formation of Inflammatory Cancer-Associated Fibroblasts Via NF-kB/CXCL1/STAT3 in Esophageal Squamous Cell Carcinoma.
Authors: Fang Lingling , Che Yun , Zhang Chaoqi , Huang Jianbing , Lei Yuanyuan , Lu Zhiliang , Sun Nan , He Jie 
Published: January 2021

Abstract
Background: The tumor microenvironment (TME) consists of a variety of cells that interact with each other through cytokines. As an important member of the TME, cancer-associated fibroblasts (CAFs) play an important role in the development of tumor cells, which is influenced by the heterogeneity of CAFs. Transforming growth factor β (TGFβ) not only plays a dual role in the progression of tumor cells directly but also influences tumor cells by regulating the heterogeneity of CAFs. Methods: we explored oncogenes regulated by TGFβ, which were involved in signaling molecules and interactions in the TME. We analyzed sequencing data of TCGA and GSE53625, as well as ESCC cell lines with or without TGFβ1 stimulation, and then we focused on laminin subunit gamma 1 (LAMC1). The upregulation of LAMC1 after TGF-β1 stimulation was examined by western blot (WB), quantitative real time PCR (qRT-PCR) and Chromatin immunoprecipitation (ChIP). We performed gain-of-function and loss-of-function assays to examine the effect of LAMC1 on proliferation and migration of ESCC cells. CAFs were isolated and cocultured with ESCC cells. And conditional medium of shLAMC1 ESCC cells and CAFs with different treatments were collected. RNA-seq of those cells were also performed. Luminex liquid suspension chip detection, ELISA, WB, qRT-PCR and rescue experiments were carried out to reveal the interaction of between ESCC cells and CAFs.Results: LAMC1 was highly expressed in ESCC, affecting the prognosis of patients. Moreover, LAMC1 could be upregulated by TGFβ1 through SMAD4 and SP1 synergistic activation. Further experiments showed that LAMC1 would promote the proliferation and migration of tumor cells mainly via Akt/NF-κB/MMP9 and MMP14. Additionally, LAMC1 would promote CXCL1 secretion mainly by activating NF-κB. Tumor-secreted CXCL1 remodeled the formation of inflammatory CAFs (iCAFs) through CXCR2/pSTAT3. The conditioned medium of iCAFs promoted the proliferation and migration of tumor cells.Conclusions: Our study identified the mechanism by which upregulation of LAMC1 by TGFβ in tumor cells not only promoted ESCC progression but also indirectly induced carcinogenesis by stimulating CXCL1 secretion and promoting the formation of iCAFs. This suggests that LAMC1 could be a potential therapeutic target and prognostic marker for ESCC.
APOE is a Prognostic Biomarker and Correlates With Immune Infiltrates in Papillary Thyroid Carcinoma
Authors: Lin Xu , Zhang Wen-Jing , Xue Gang , Wu Jing-Fang , Chao Liu-ya 
Published: January 2021

Abstract
Background: Recent research showed that abnormal lipid metabolism was associated with cancers. As one of the genes that can regulate the level of lipid metabolism, abnormal APOE expression was associated with carcinogenesis. However, the biological role of APOE in papillary thyroid carcinoma (PTC) remains to be determined.Methods: ONCOMINE, GEPIA, UALCAN, STRING, GeneMANIA, LinkedOmics, GSCALite, TISIDB, EPIC and TIMER were utilized to achieve comprehensively bioinformatics analysis of APOE in this study. And the immunohistochemical staining of APOE was used to verify the predicted results.Results: The mRNA level and protein level of APOE of PTC tissues were significantly elevated in TCGA cohort and Shanghai cohort. And APOE expression was positively correlated with the pathological stage and lymph node metastasis in PTC. PTC patients with low mRNA level of APOE were associated with a bad prognosis. The functions of APOE co-expressed genes were mainly enriched in adaptive immune response, protein-lipid complex subunit organization, actin cytoskeleton reorganization, cell chemotaxis, protein activation cascade and transcriptional misregulation in cancer. APOE level was significantly correlated with tumor-infiltrating cells (B cells, CD8+ T cells, neutrophils, and dendritic) and immune biomarkers in PTC.Conclusions: APOE is a potential independent biomarker for PTC and APOE expression is positively correlated with immune cell infiltration in PTC.
Alteration of 3d Matrix Stiffness Regulates Viscoelasticity of Human Mesenchymal Stem Cells
Authors: Kao Ting-Wei , Chiou Arthur , Lin Keng-Hui , Liu Yi-Shiuan , Lee Oscar 
Published: January 2021

Abstract

Background: Human mesenchymal stem cells (hMSCs) possess potential of bone formation and were proposed as ideal material for tissue regeneration against osteoporosis. Although a plethora of elucidation regarding the directing effect on lineage specification by physical cues has been proposed, how mechanical stimulations impact the intracellular viscoelasticity during osteo-lineage commitment remained enigmatic. Methods: Cyto-friendly 3D matrix was prepared on soft-lithographed device. The substrate was basically polyacrylamide and conjugated with fibronectin. Stiffness of the scaffolds was determined by the mixing ratio of monomer and crosslinker. The hMSCs were injected with fluorescent beads by gene gun before being cultured in the matrix and chemically induced toward osteogenesis. The mechanical properties were assessed using video particle tracking microrheology. On post-induction day 0, 7, 14, 21, inverted epifluorescence microscope with charge-coupled camera was exploited to capture the projected Brownian trajectory of indwelling hMSCs. Mean square displacement thereof was calculated and transformed into intracellular viscoelasticity by generalized Stokes-Einstein equation.Results: Two different stiffness of 3D culture microspheres (12 kPa, 1 kPa) were established. A total of 45 cells were assessed. Initially, hMSCs possessed equivalent mechanical traits in the first week. Nonetheless, cells cultured in rigid matrix displayed statistically significant elevation over elastic (G’) and viscous moduli (G”) on day 7 (G’: 192±8 vs. 114±8, p<0.01; G” 204±9 vs. 169±10 Pa, p<0.01) and day 14 (G’: 190±6 vs. 129±7, p<0.01; G” 222±10 vs. 161±9 Pa, p<0.01). To appreciate the trend of fluctuation, subsequent measurements were compared with the respective modulus at day 0. The soft niches no longer facilitated stiffening hMSCs, whereas the effect by rigid substrates was consistently during the entire differentiation course.Conclusions: Stiffness of the matrix impacted the viscoelasticity of hMSCs. Detailed elucidation on how microenvironment impacts mechanical properties and differentiation of hMSCs will facilitate the advancement of tissue engineering and regenerative medicine.
LncRNA FBXL19-AS1 Promotes Proliferation and Metastasis of Cervical Cancer Through Upregulating COL1A1 as a Sponge of MiR-193a-5p
Authors: Huang Xiaoyong , Shi Haiyan , Shi Xinghai , Jiang Xuemei 
Published: January 2021

Abstract
Background: Cervical cancer (CC) is one of the most common and malignant tumors in women. In this study, we aim to explore the role and mechanism of FBXL19-AS1, a novel long-chain non coding RNA with marked roles in a variety of tumors, in regulating the proliferation and metastasis of CC. The expression of FBXL19-AS1, miR-193a-5p and COL1A1 were detected by RT-PCR and western blot. Gain-and loss- of functions of FBXL19-AS1 and miR-193a-5p were performed in CC cell lines in vitro. The proliferation, migration, invasion, apoptosis and epithelial-mesenchymal transition (EMT) level were determined. Results: FBXL19-AS1 and COL1A1 were significantly up-regulated in CC, while miR-193a-5p was significantly down-regulated. Overexpression of FBXL19-AS1 significantly promoted the proliferation, migration, invasion and EMT of CC cells and inhibited apoptosis, while knockdown of FBXL19-AS1 had the opposite effects. On the other hand, miR-193a-5p inhibited the proliferation and metastasis of CC cells. Mechanistically, FBXL19-AS1 functioned as a competitive endogenous RNA and inhibited the expression of miR-193a-5p, which targeted at the 3'-UTR site of COL1A1 and negatively regulated COL1A1 expression. Concluson: FBXL19-AS1 can promote the proliferation and metastasis of CC by sponging miR-193a-5p and up-regulating COL1A1.
Premorbid cardioselective (but not non-selective) β-blocker exposure reduces intensive care unit mortality among septic patients
Authors: Kuo Ming-Jen , Chou Ruey-Hsing , Lu Ya-Wen , Guo Jiun-Yu , Tsai Yi-Lin , Wu Cheng-Hsueh , Huang Po-Hsun , Lin Shing-Jong 
Published: January 2021

Abstract
Background

β blockers may protect against catecholaminergic myocardial injury in critically ill patients. Long-term β-blocker users are known to have lower lactate concentrations and favorable sepsis outcomes. However, the effects of cardioselective and nonselective β-blockers on sepsis outcomes have not been compared. This study was conducted to investigate the impacts of different β-blocker classes on the mortality rate in septic patients.
Methods

We retrospectively screened 2678 patients admitted to the medical or surgical intensive care unit (ICU) between December 2015 and July 2017. Data from patients who met the Sepsis-3 criteria at ICU admission were included in the analysis. Premorbid β-blocker exposure was defined as the prescription of any β-blocker for at least 1 month. Bisoprolol, metoprolol, and atenolol were classified as cardioselective β-blockers, and others were classified as nonselective β-blockers. All patients were followed for 28 days or until death.
Results

Among 1262 septic patients, 209 (16.6%) patients were long-term β-blocker users. Patients with premorbid β-blocker exposure had lower heart rates, initial lactate concentrations, and ICU mortality. After adjustment for disease severity, comorbidities, blood pressure, heart rate, and laboratory data, reduced ICU mortality was associated with premorbid cardioselective [adjusted hazard ratio (HR), 0.28; 95% confidence interval (CI), 0.11–0.74; P = 0.010], but not non-selective (adjusted HR, 0.78; 95% CI, 0.30–2.05; P = 0.611), β-blocker use.
Conclusion

Premorbid cardioselective, but not non-selective, β-blocker use was associated with improved mortality in septic patients. This finding supports the protective effect of cardioselective β-blockers in septic patients. Prospective studies are needed to confirm it.