bluuebunny/crossref_metadata_2025_split huggingface dataset:
Propensity-score Matching Analysis for Marital Status and Survival of Oral and Oropharyngeal Squamous Cell Carcinoma Based on SEER Database
Authors: Ming Wei , Zuo Jingjing , Han Jibo , Wang Yan , Chen Jinhui 
Published: November 2021

Abstract
ObjectMarital status plays different roles as a risk factor on survival in various cancers . The study is aimed to analyze the impact of marital status on survival of oral and oropharyngeal squamous cell carcinoma(OPSCC) at population level based on SEER database using propensity-score matching method(PSM).Methods37,023 eligible patients were extracted from the Surveillance, Epidemiology, and End Results(SEER) database, and analyzed the impact of various marital status on cancer-specific survival(CSS) of OPSCC by Kaplan-Meier method and Cox regression model. Then we used propensity-score matching analysis to balance baseline characteristics between married, single, divorced and widowed patients. The impact of various marital status after pairwise matching using p-value adjusted and PSM on CSS was re-analyzed by Kaplan-Meier method.ResultsThe age, sex, race, tumor location, pathologic grades, SEER stages, treatments, composite socioeconomic status(C-SES), insurance, and marital status were identified as independent prognostic factors for CSS of OPSCC. Widowed patients presented the worst CSS, compared with married, single, and divorced patients(P<0.001). Subgroup analysis indicated that widowed patients always presented with the significantly decreasing risk of CSS compared with other marital status in different SEER stages(P<0.001), and different C-SES(P<0.001). After propensity-score matching, widowed patients were still found to be associated with significantly decreased CSS compared with other marital groups(P<0.001).Conclusion﻿Marital status was first analyzed after using PSM to balance clinicopathological and socioeconomic confounding factors and identified as an independent prognostic factor for CSS of OPSCC. Widowed patients was significantly associated with a decreasing CSS, which indicated that absence of spousal support and optimal psychosocial coping strategies may explain the phenomenons.
4SC-202 Exerts An Anti-tumor Effect in Cervical Cancer By Targeting PRLR Signaling Pathway
Authors: Zhang Huijuan , Li Mingxia , Yang Wen , Ye Mingxia , Li Hua , Meng Yuanguang 
Published: November 2021

Abstract
The aim of the present study is to investigate whether 4SC-202, a selective class I histone deacetylase inhibitor (HDACi), plays an anti-tumor role in cervical cancer (CC) by targeting prolactin receptor (PRLR). CCK-8 and colony formation assays were used to evaluate the effects of 4SC-202 on the proliferation of CC cells in vitro. Effects of 4SC-202 on the cell cycle distribution and apoptosis in SiHa cells were determined by flow cytometry and western blotting, respectively. Immunofluorescence and western blotting were performed to detect the activities of PRLR-related pathways and PRLR expression in CC cells. A xenograft tumor model in nude mice was established to examine effects of 4SC-202 on the tumor growth, apoptosis and PRLR-related pathways in vivo. The biochemical analyzer and H&E staining were used to detect the serum biochemical indexes and organ toxicity. 4SC-202 inhibited the proliferation of CC cells (SiHa, HeLa, and CaSki) in vitro in a time- and dose-dependent manner. SiHa cells were treated with 1 or 5 μM 4SC-202 for 72 h and then subjected to various functional assays. The assays showed that 4SC-202 significantly induced G2/M phase arrest and apoptosis, while inhibiting the activities of PRLR-related pathways and PRLR expression. In addition, 4SC-202 reduced tumor growth and induced apoptosis in vivo. 4SC-202 down-regulated the expression of PRLR and activities of PRLR-related pathways in the mouse model, displayed no effects on serum biochemical indicators and caused no toxicity to mouse organs. This finding suggests that 4SC-202 may serve as a novel therapeutic agent for CC.
Structure Clearance Design in Wind Tunnel Tests with Implications for Aerodynamic Drag of High-Speed Trains
Authors: Huang Zhixiang , Huang Hanjie , Zeng Weiping , Chen Li , Zhu Renyu 
Published: November 2021

Abstract
The influences of vestibule diaphragm gap, wheel-rail clearance, and strut-plate gap on the aerodynamic drag of a 1/8th-scale high-speed train model were investigated in an 8 m×6 m wind tunnel. The Reynolds number was set to 2.2×106 based on train height. It was found that the variation of the vestibule diaphragm gap changed the aerodynamic drag distribution pattern of each car; the drag coefficient of the head and middle cars might change as high as 45%; however, the change in the drag coefficient of the total train was very small. The effects of the strut-plate gap on the aerodynamic drag of each car and the total train were small. The effect of the wheel-rail clearance on the drag of the head car was not significant. It was suggested that the vestibule diaphragm gap, strut-plate gap and wheel-rail clearance of the 1:8 scale high-speed train model should not be greater than 11, 10, and 9 mm, respectively.
A novel heterozygous ZBTB18 missense mutation in a family with non-syndromic intellectual disability and structural brain abnormalities
Authors: Li Nana , Wang Meixian , Zou Yanna , Liu Zhen , Deng Ying , Qin Hong , Qiu Xiaoqiong , Kang Hong , Wang Yanping , Zhu Jun , Agostino Mark , Heng Julian I-T , Yu Ping 
Published: November 2021

Abstract
Background
Intellectual Disability (ID) is a characterized by significantly impaired adaptive behavior and cognitive capacity. Currently, high throughput sequencing approaches have led to the identification of genetic causes for ID in 25-50% of cases, while the causes of inherited ID are less well known. Here, we have investigated the genetic cause for non-syndromic ID in a Han Chinese family.
Methods
Whole genome sequencing was performed on identical twin sisters diagnosed with ID, their respective children as well as their asymptomatic parents. Data was filtered for rare variants and in silico prediction tools used to establish pathogenic alleles. Candidate mutations were validated by Sanger sequencing. Molecular modelling was conducted to establish the effects of the mutation on the protein encoded by a candidate coding gene.
Results
A novel heterozygous variant in the ZBTB18 gene c.1323C>G (p.His441Gln) was identified. This variant co-segregated with affected individuals in an autosomal dominant pattern and was not detected in asymptomatic family members. Molecular studies reveal that a p.His441Gln substitution disrupts the coordination of a zinc ion within the second zinc finger and disrupts the capacity for ZBTB18 to bind DNA.
Conclusions
c.1323C>G mutation in ZBTB18 gene on 1 chromosome may be related with the phenotype of intellectual disability in this family. WGS is an efficient method to perform molecular diagnosis for hereditary ID. This is the first report of an inherited ZBTB18 mutation for ID and suggests that mutations that disrupt C2H2 motifs underlie human neurodevelopmental disorder.
A Water-Soluble Manganese(II) Octanediaoate/Phenanthroline Complex Acts as an Antioxidant and Attenuates Alpha-Synuclein Toxicity
Authors: Queiroz Daniela Dias , Ribeiro Thales de Paula , Gonçalves Julliana M. , Mattos Larissa M. M. , Gerhardt Ellen , Freitas Júlia , Palhano Fernando L. , Frases Susana , Pinheiro Anderson S. , McCann Malachy , Knox Andrew , Devereux Michael , Outeiro Tiago F. , Pereira Marcos D. 
Published: November 2021

Abstract
The overproduction of reactive oxygen species (ROS) induces oxidative stress, a well-known process associated with aging and several human pathologies, such as cancer and neurodegenerative diseases. A large number of synthetic compounds have been described as antioxidant enzyme mimics, capable of eliminating ROS and/or reducing oxidative damage. In this study, we investigated the antioxidant activity of a water-soluble 1,10-phenantroline-octanediaoate Mn2+-complex on cells under oxidative stress, and assessed its capacity to attenuate alpha-synuclein (aSyn) toxicity and aggregation, a process associated with increased oxidative stress. This Mn2+-complex exhibited a significant antioxidant potential, reducing intracelular oxidation and increasing oxidative stress resistance in S. cerevisiae cells and in vivo, in G. mellonella, increasing the activity of the intracellular antioxidant enzymes superoxide dismutase and catalase. Strikingly, the Mn2+-complex reduced both aSyn oligomerization and aggregation in human cell cultures and, using NMR and DFT/molecular docking we confirmed its interaction with the C-terminal region of aSyn. In conclusion, the Mn2+-complex appears as an excellent lead for the design of new phenanthroline derivatives as alternative compounds for preventing oxidative damages and oxidative stress - related diseases.
A pan-cancer analysis of the glutaminase and their association with prognosis, tumor microenvironment, and therapeutic targets
Authors: Jin Sheng-Jie , Kong Lian-bao 
Published: November 2021

Abstract
BackgroundGlutamine metabolism plays a key role in various biological processes of tumor. Glutaminase (GLS) is involved in Glutamine metabolism and plays a conserved regulatory role in the process. Nevertheless, there is no comprehensively analysis of GLS in pan-cancer.MaterialsComprehensive bioinformatics analysis was adopted to investigate the expression level, prognostic values, and association between expression of GLS and TME, immune cells' infiltration, immune checkpoint genes, TMB, MSI, drug sensitivity in pan-cancer. Bioinformatics tools including CCLE, immunophenoscore (IPS), Tumor Immune Dysfunction and Exclusion (TIDE), GSEA, and TIMER databases were used.ResultsDifferently expressed GLS between tumor and normal tissues were analyzed, and the clinical prognoses, MMR, MSI, and TMB in multiple types of cancer were associated with GLS expression. Furthermore, GLS closely correlated with tumor immunity and drug sensitivity, and found GLS were predicted to be involved in cancer metabolism and immunity pathways, through gene set enrichment analysis (GSEA).ConclusionThe GLS expression could be used as a prognostic biomarker for determining prognosis and provide further insights into anti-glutamine metabolism for cancer.
Chondrocyte Targeting Gold Nanoparticles Protect Growth Plate Against Inflammatory Damage By Maintaining Cartilage Balance
Authors: Bai Xue , Sun Hongyan , Jia Lina , Xu Junjie , Zhang Peng , Chen Bo , Zhang Deyuan , Feng Lin 
Published: November 2021

Abstract
Background: Cartilage destruction caused by inflammation is a clinical challenge. Many studies have investigated cartilage destruction in adults, but little research was conducted on children. Results: The gaps without chondrocytes and ECM between the proliferative and hypertrophy zones of the GP cartilage were formation after the treatment of LPS, but the gaps were not observed in the AuNPs + LPS group. This finding can be attributed to the capability of AuNPs to target to the chondrocytes and reduce the release of inflammatory cytokines and secretion of ECM degradation factors induced by LPS. And then, the LPS-induced apoptosis rate of mouse chondrocytes and ECM degradation rate were inhibited. Finally, the balance of catabolic and anabolic factors in the ECM was maintained.Conclusion: These findings indicate that AuNPs can partially protect the cartilage of children from inflammatory damage by suppressing chondrocyte apoptosis and ECM degradation.
Role of Glial Cell Line-Derived Neurotrophic Factor in Adipose Tissue Extract-Induced Angiogenesis in Mice
Authors: Zhou Renpeng , Yin Chuang , Bian Weiwei , Wang Chen 
Published: November 2021

Abstract
Our present study is aimed to evaluate the effects of adipose-derived extracts (AT-Ex) and GDNF within the extracts on skin graft. AT-Ex was harvest from fresh human lipoaspirates with centrifugation, emulsification and lysing by cycles of freeze and thawing. Concentrations of GDNF, VEGF and bFGF were detected by ELISA. AT-Ex and anti-GDNF-antibody-coupled AT-Ex were further used to test their ability to promote tube formation using human umbilical vein endothelial cells (HUVECs) and stimulate angiogenesis in nude skin-graft models. The results demonstrated that abundant GDNF, VEGF and bFGF were detected in AT-Ex, with GDNF displaying the highest concentration. AT-Ex significantly promoted the tube formation ability of HUVECs in vitro, with a dosage-dependent manner, while this ability was partially impaired when the anti-GDNF antibody was conjugated. In vivo, The AT-Ex treatment increased dermal thickness, augmented dermal proliferation and increased vascular density and GDNF contributed greatly to the AT-Ex effect in improvement the grafted skin condition by promoting angiogenesis in vivo. Our results suggested that critical effect of GDNF from AT-Ex on improvement skin graft condition.
KLF14 targets ITGB1 to inhibit the progression of cervical cancer via the PI3K/AKT signalling pathway
Authors: Lyu Xinran , Ding Xuchao , Ye Hui , Guo Rong , Wu Minhang , Cao Lili 
Published: November 2021

Abstract
Background
Our study aimed to explore whether Krüppel-like factor 14 (KLF14) inhibits the proliferation and promotes the apoptosis of cervical cancer cells through integrin β1 (ITGB1).
Methods
Immunohistochemistry was used to explore the expression of KLF14 in cervical cancer tissues and adjacent samples.The effect of KLF14 on the proliferation of cervical cancer cells was verified by Cell Counting Kit-8 (CCK-8) assays, colony formation assays and an animal experiment (involving subcutaneous tumour formation in nude mice). The effect of KLF14 on cervical cancer cell apoptosis was detected by flow cytometry. To explore the underlying mechanisms, western blotting was conducted to detect the expression of ITGB1 in KLF14-overexpressing cervical cancer cells. Moreover, downstream related proteins were verified to further confirm that KLF14 targets ITGB1 to affect the apoptosis of cervical cancer cells. We conducted relevant rescue experiments, flow cytometry was used to verify the effect of overexpression of ITGB1 and simultaneous overexpression of ITGB1 and KLF14 on apoptosis of cervical cancer cells, and western blot analysis was used to investigate the expression of downstream related proteins after overexpression of ITGB1 and simultaneous overexpression of ITGB1 and KLF14.
Results
The expression of KLF14 in cervical cancer tissues was lower than that in paracancerous tissues. KLF14 inhibited the proliferation and promoted the apoptosis of cervical cancer cells. Mechanistically, ITGB1 expression was significantly downregulated in KLF14-overexpressing cervical cancer cells. KLF14 targets ITGB1 to regulate its downstream PI3K/AKT signalling pathway. The upregulation of ITGB1 can inhibit the apoptosis of cervical cancer cells by affecting the downstream PI3K/AKT signalling pathway, and the upregulation of KLF14 can reverse the effect of ITGB1 upregulation on cervical cancer cell apoptosis to a certain extent.
Conclusions
KLF14 inhibits the progression of cervical cancer by targeting ITGB1 via the PI3K/AKT signalling pathway.
Contrast-enhanced Ultrasound Imaging Using Capacitive Micromachined Ultrasonic Transducers
Authors: Øygard Sigrid Husebø , Ommen Martin L. , Tomov Borislav G. , Diederichsen Søren E. , Thomsen Erik V. , Larsen Niels B. , Stuart Matthias B. , Jensen Jørgen A. 
Published: November 2021

Abstract
Capacitive micromachined ultrasonic transducers (CMUTs) have a nonlinear relationship between the applied voltage and the emitted signal, which is detrimental to conventional contrast-enhanced ultrasound (CEUS) techniques. Instead, a three-pulse amplitude modulation (AM) sequence has been proposed, which is not adversely affectedby the emitted harmonics. In this paper, this is shown theoretically, and the performance of the sequence is verified using a 4.8 MHz linear CMUT array, and a comparable lead zirconate titanate (PZT) array, across 6 V to 60 V applied AC voltage. CEUS images of the contrast agent SonoVue flowing through a 3D printed hydrogel phantom showed an average enhancement in contrast-to-tissue ratio (CTR) between B-mode and CEUS images of 49.9 dB and 37.4 dB for the PZT array and CMUT, respectively. Furthermore, hydrophone recordings of the emitted signals showed that the nonlinear emissions from the CMUT did not significantly degrade the cancellation in the compounded AM signal, leaving an average of 2% of the emitted power between 26 V and 60 V AC. Thus, it is demonstrated that CMUTs are capable of CEUS imaging independent of the applied excitation voltage when using a three-pulse AM sequence.
Immune-Related Matrisomes are Potential Biomarkers to Predict the Prognosis and Immune Microenvironment of Glioma Patients Through Bioinformatics Analysis and Experimental Verification
Authors: Yu Hao , Wang Minjie , Wang Xuan , Jiang Xiaobing 
Published: November 2021

Abstract
Purpose

The extracellular matrix (ECM) plays a vital role in the progression and metastasis of glioma and is an important part of the tumor microenvironment. However, there are few studies on the overall role of the ECM in the glioma immune microenvironment. This study aimed to analyze the prognosis of matrisomes in patients with glioma.
Methods

Overall, 676 glioma patients in The Cancer Genome Atlas (TCGA) database were divided into the low, moderate, and high immune infiltration groups. Immune-related matrisomes differentially expressed among the three groups were analyzed, and a risk signature was established. Eight immune-related matrisomes were screened, namely, LIF, LOX, MMP9, S100A4, SRPX2, SLIT1, SMOC1, and TIMP1. Kaplan Meier analysis, operating characteristic curve (ROC) analysis and nomogram were constructed to analyze the relationships between risk signatures and the prognosis of glioma patients.
Results

The risk signature was significantly correlated with the overall survival (OS) of glioma patients. Both high- and low-risk signatures were also associated with some immune checkpoints. In addition, analysis of somatic mutations and anti-PD1/L1 immunotherapy responses in the high- and low-risk groups showed that the high-risk group had worse prognosis and a higher response to anti-PD1/L1 immunotherapy. qPCR and immunohistochemical analysis showed that LIF, LOX, MMP9, S100A4, SRPX2 and TIMP1 were highly expressed in glioma, while SLITI1 and SMOC1 were low expressed in glioma.
Conclusions

Matrisomes play a vital role in the complex immune microenvironment of gliomas. Our analysis of immune-related matrisomes can improve understanding of the characteristics of the glioma immune microenvironment and provide important clues for glioma immunotherapy in the future.
The Association Between Multimorbidity and Health-Related Quality of Life Among Clients Attending Chronic Outpatient Medical Care in Bahir Dar, Northwest Ethiopia: The Application of Partial Proportional Odds Model
Authors: Eyowas Fantu Abebe , Schneider Marguerite , Alemu Shitaye , Pati Sanghamitra , Getahun Fentie Ambaw 
Published: November 2021

Abstract
Background Multimorbidity, the presence of two or more chronic non-communicable diseases (NCDs) in a given person affects all aspects of individuals’ lives. Poor quality of life (QoL) is one of the major consequences of living with multimorbidity. Although healthcare aims to support multimorbid individuals to achieve better quality of life, little is known about the effect of multimorbidity on quality of life of patients attending chronic outpatient medical care in Ethiopia. Objectives This study aimed to determine the association between multimorbidity and quality of life among clients attending chronic outpatient medical care in Bahir Dar city, Northwest Ethiopia. Methods A multi-centered facility-based study was conducted among 1440 participants aged 40+ years attending chronic outpatient medical care. Two complementary methods (interview and review of medical records) were employed to collect data on sociodemographic characteristics and presence of chronic diseases. We used the short form (SF-12 V2) instrument to measure quality of life. The data were analyzed by STATA V.16 and multivariate partial proportional odds model was fitted to identify covariates associated with quality of life, adjusting for relevant confounding factors. Statistical significance was considered at p-value <0.05.Results Multimorbidity was identified in 54.8% (95% CI=52.2%-57.4%) of the sample. A significant proportion (33.5%) of the study participants had poor quality of life and one fourth (25.8%) of them had moderate quality of life. Advanced age and living with multimorbidity were associated with poor quality of life. Conversely, being female, strong social support, high socioeconomic status, and adequate functioning and satisfaction with care were the variables positively associated with higher categories of quality of life.Conclusion The magnitude of multimorbidity in this study was high and individuals living with multimorbidity had a relatively poor quality of life than those without multimorbidity. Care of people with chronic multiple conditions may need to be oriented to the realities in multimorbidity burden and its implication on quality of life. Interventions targeting modifiable associated factors and studies exploring the longitudinal effect of multimorbidity on quality of life are needed.
Comparison of the Antibacterial Activity of Australian Terminalia Spp. Extracts Against Klebsiella Pneumoniae: Novel Treatment for Ankylosing Spondylitis
Authors: Cock Ian , Courtney Reece 
Published: November 2021

Abstract
Traditional medicines prepared using Terminalia species have been used globally to treat inflammation and pathogenic infections. Recent studies have demonstrated that multiple Asian and African Terminalia spp. inhibit bacterial triggers of some autoimmune inflammatory disease, including ankylosing spondylitis. Despite this, the effects of Australian Terminalia spp. on a bacterial trigger of ankylosing spondylitis (K. pneumoniae) remain unexplored. Fifty-five extracts from five Australian Terminalia spp. were investigated for K. pneumoniae growth inhibitory activity. Methanolic, aqueous and ethyl acetate extracts of most species and plant parts inhibited K. pneumoniae growth, with varying potencies. Methanolic leaf extracts were generally the most potent bacterial growth inhibitors, with MIC values of 66 µg/mL (T. ferdinandiana), 128 µg/mL (T. carpenteriae) and 83 µg/mL (T. petiolares). However, the aqueous leaf extract was the most potent T. grandiflora extract (MIC = 87 µg/mL). All T. catappa extracts displayed low growth inhibitory activity. The Terminalia spp. methanolic leaf extracts were examined by LC-MS and GC-MS. All contained a relative abundance of simple gallotannins (particularly gallic and chebulic acids), the flavonoid luteolin, as well as the monoterpenoids cineole and terpineol. Notably, all Terminalia spp. were non-toxic or of low toxicity in ALA and HDF toxicity assays, highlighting their potential for preventing the onset of ankylosing spondylitis and treating its symptoms once the disease is established.