bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anlotinib Inhibits the Growth of Breast Cancer Cells by Promoting Autophagy and Apoptosis via the Akt/GSK-3α&nbsp;Signalling Pathway
Authors: Chen Shuyi , zhu ping , wang xue , jin youping , zhi xiuling , Yang Huanjun , zhou ping 
Published: December 2020

Abstract
Background: Anlotinib, a multi-target tyrosine kinase inhibitor, has already been indicated to have significant anticancer effects on lung cancer, colon cancer and ovarian cancer in a phase II clinical trial, but its effect on breast cancer (BC) has not been adequately investigated. Methods: The proliferation activity of BC cell lines MCF-7 and MDA-MB-231 with the treatment of anlotinib was tested by Cell Counting Kit-8 (CCK-8) assay and immunocytochemistry (ICC) staining. We investigated the alteration of cell cycle and apoptosis and autophagy level and the underlying mechanism in the cell lines by quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR), Western blots, ICC and TUNEL staining and flow cytometry. Further, AT-3 cells were subcutaneously injected into C57BL/6 mice, followed by anlotinib intragastrically. The extracted tumours were assessed by qRT-PCR, Western blots and immunohistochemistry.Results: We found that anlotinib suppressed the cell viability and proliferation of MCF-7 and MDA-MB-231 cell lines and tumour growth in BC xenografts in mice, likely due to abnormal cell cycle arrest and induction of autophagy and apoptosis. Then, we further examined the underlying mechanism of anlotinib, and the results indicated that anlotinib induced apoptosis by promoting autophagy in MCF-7 and MDA-MB-231 cells by regulating the Akt/GSK-3α pathway. The analysis of data from patients with BC collected in TCGA revealed that increased VEGFA expression was related to BC.Conclusions: Our study demonstrated that anlotinib inhibited the growth of BC cells via promoting apoptosis through autophagy mediated by Akt/GSK-3α signalling and may be an effective new drug for BC treatment.
Cardiovascular Disease in Women with Breast Cancer – A Nationwide Registry Study
Authors: Jakobsen Marie , Kolodziejczyk Christophe , Jensen Morten Sall , Poulsen Peter Bo , Khan Humma , Kümler Thomas , Andersson Michael 
Published: December 2020

Abstract
Background: There is increasing concern about cardiovascular disease (CVD) after breast cancer (BC). The aim of this study was to estimate the prevalence of different types of CVD in women diagnosed with BC compared to cancer-free controls as well as the incidence of CVD after BC diagnosis.Methods: We performed a cohort study based on data from national registries covering the entire Danish population. We followed 16,505 cancer-naïve BC patients diagnosed from 2003 to 2007 five years before and up to 10 years after BC diagnosis compared to 165,042 cancer-free controls. Results: We found that 15.6% of BC patients were registered with at least one CVD diagnosis in hospital records before BC diagnosis. Overall, BC patients and controls were similar with regards to CVD comorbidity before BC diagnosis. After BC diagnosis, the incidence of all CVD diagnoses combined was significantly higher in BC patients than controls up to approximately 6 years after the index date (BC diagnosis). The incidence of heart failure, thrombophlebitis/thrombosis and pulmonary heart disease including pulmonary embolism remained higher in BC patients than controls during the entire 10 year follow-up period. Furthermore, we found that the risk of heart failure and thrombophlebitis/thrombosis was higher after chemotherapy. Conclusions: Focus on CVD in BC patients is important to ensure optimum treatment with regards to BC as well as possible CVD. Strategies to minimise and manage the increased risk of heart failure, thrombophlebitis/thrombosis and pulmonary heart disease including pulmonary embolism in BC patients are especially important.
One Repeated Transplantation of Allogeneic Umbilical Cord Mesenchymal Stromal Cells in Type 1 Diabetes: An Open Parallel Controlled Clinical Study
Authors: Lu Jing , Shen Shanmei , Ling Qing , Zhang Wei , Qu Duoduo , Wang Bin , Bi Yan , Zhu Dalong 
Published: December 2020

Abstract
Background: The preservation or restoration of b-cell function in type 1 diabetes (T1D) remains as an attractive and challengeable therapeutic target. Mesenchymal stromal cells (MSCs) are multipotent cells with high capacity of immunoregulation, which emerged as a promising cell-based therapy for many immune disorders. The objective of this study was to examine the efficacy and safety of one repeated transplantation of allogeneic MSCs in individuals with T1D. Methods: This was a nonrandomized, open-label, parallel-armed prospective study. MSCs were isolated from umbilical cord (UC) of healthy donors. 53 participants including 33 adult-onset (³18 years) and 20 juvenile-onset T1D were enrolled. 27 subjects (MSC-treated group) received an initial systemic infusion of allogeneic UC-MSCs, followed by a repeat course at 3 months, whereas the control group (n=26) only received standard care based on intensive insulin therapy. Data at one-year follow-up was reported in this study. The primary endpoint was clinical remission defined as a 10% increase from baseline in the level of fasting and/or postprandial C-peptide. The secondary endpoints included side effects, serum levels of HbA1c, changes in fasting and postprandial C-peptide, and daily insulin doses. Results: After 1-year follow-up, 40.7% subjects in MSC-treated group achieved the primary endpoint, significantly higher than that in the control arm. Three subjects in MSC-treated group, in contrast to none in control group, achieved insulin independence and maintained insulin free for 3 to 12 months. Among the adult-onset T1D, the percent change of postprandial C-peptide was significantly increased in MSC-treated group than in the control group. However, changes in fasting or postprandial C-peptide was not significantly different between groups among the juvenile-onset T1D. Multivariable logistic regression assay indicated that lower fasting C-peptide and higher dose of UC-MSC correlated with achievement of clinical remission after transplantation. No severe side effects were observed. Conclusion: One repeated transplantation of allogeneic UC-MSCs is both safe and beneficial to preserve b-cell function for individuals with T1D. Trial registration: NCT 02763423. Registered on April 19, 2016 - Retrospectively registered, https://clinicaltrials.gov/
Effect Of Prior Cancer History on The Survival of Gallbladder Cancer Patients: A Propensity Score Matching Study Based on The SEER Database
Authors: Ren Jie , Liu Wei , Li Qinglin , Cui Ruixia , Tong Yingmu , Qu Kai , Liu Chang , Zhang Jingyao 
Published: December 2020

Abstract
Background: The effect of previous malignancy history on the survival of individuals with a second primary gallbladder cancer remains unclear. Therefore, this study was conducted to analyze the impact of previous malignancy history on the survival of individuals with gallbladder cancer and to compare the prognostic differences between gallbladder cancer patients with and without previous cancer.Methods: Extract the United States Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015 for cases diagnosed with gallbladder cancer. The Kaplan-Meier curves and log-rank test were used to compare the survival difference between gallbladder cancer individuals with and without previous malignancy. Cox proportional hazards regression model was used to explore the risk factors of gallbladder cancer.Results: A total of 5861 patients with gallbladder cancer were enrolled, including 5622 (95.9%) patients without prior primary cancer and 239 (4.1%) patients with prior primary cancer. Patients with gallbladder cancer with prior primary malignancy were older, and the tumors were at localized and regional stages more frequently and more early stages. The Kaplan-Meier curves showed that gallbladder cancer patients with prior cancer had better overall survival (OS) (P=0.027) and gallbladder cancer-specific survival (GCSS) (P<0.001) before propensity score matching (PSM), and gallbladder cancer patients with prior cancer had better GCSS (P<0.001), and there was no difference in OS (P=0.113) between gallbladder cancer patients with and without prior cancer after PSM. Multivariable cox regression analysis revealed that prior malignancy history was not a risk factor for OS (HR=0.875, 95%CI: 0.752-1.018, P=0.084), but it was beneficial to GCSS (HR=0.404, 95%CI: 0.318-0.513, P<0.001).Conclusions: Gallbladder cancer individuals with previous primary malignancy have different clinical characteristics from those without previous primary malignancy. Gallbladder cancer patients with previous primary malignancy have better progress than those without previous malignancy.
The Deaf and Hard-Hearing and their Perception of Music
Authors: Bahl Hanshul 
Published: December 2020

Abstract
The qualitative case study investigates how Deaf students participate in music in a number of ways and from a variety of backgrounds, including their own experience of education. The event involved a school that provided a music programme for Deaf children and a questionnaire, interviewings, reports and documents were used to examine them. The students have been particularly interested with music by participating in the fields of sign language, song, instrument playing and vocalisation as part of the school music programme. Perhaps because of shared encounters in their music classes students’ participation with music in the neighbourhood and in the community through spontaneous music events became able to criticise the stereopropes of their family members and the community. The musical interests of the students demonstrated a primarily visual and kinaesthetic awareness of music and an emphasis on repertoire learned through the curriculum of school music. The pleasure in music of the students was decided not always by their hearing ability, but more frequently by their hearing concept. The study’s findings show that music has a presence in the Deaf community.
Combined Use of Antibiotics as a Risk Factor for Health Care–Associated Infections: A Case-Control Study
Authors: Zhang Xiao-Liang , Li Fang-bin 
Published: December 2020

Abstract
BackgroundAntibiotics are among the most frequently prescribed medications. Many studies suggest an increased risk of health care–associated infections (HAIs) among antibiotic users. However，most related studies have focused only on a single type of HAIs, but considering the complexity and extent of the subject, it is necessary to conduct extensive research. We conducted a case-control study to determine the association between antibiotic combination therapy and risk of HAIs. MethodsRetrospective case-control study in a teaching hospital in Northwest China. Cases of 216 patients were diagnosed as HAIs during hospitalization between January 2019 and December 2019. Use antibiotics on admission and before the occurrence of HAIs were compared with 428 patients without HAIs during the same period, and matched by department.ResultsNinety-one of 216 health care–associated infections, 157 of 428 Patients without health care–associated infections prescribed antibiotics on admission and before the occurrence of HAIs. After multi-variable analysis, Compared with patients without HAIs, the OR for antibiotics combination exposure in cases was 5.43 [95% confidence interval (CI) 2.62-11.24], and the OR for antibiotics exposure in cases was 0.23 (95% CI 0.12-0.43).Conclusions﻿Combined use of antibiotics increases the risk of HAIs. In addition, Use of antibiotics before the diagnosis of HAIs is conducted associated with HAIs, and is the main protective factor.
Antimicrobial Resistance Properties of Staphylococcus Aureus Isolates From Powdered Packaged Medicinal Plants and Bottle Herbal Distillates
Authors: Mashak Zohreh , Tavakoli-Far Bahareh 
Published: December 2020

Abstract
BackgroundHuman involvement in the production and processing of medicinal plants and herbal distillates caused a potential risk of microbial contamination, particularly with Staphylococcus aureus. The present research was performed to assess the prevalence and phenotypic and genotypic properties of antibiotic resistance of S. aureus bacteria isolated from diverse kinds of powdered packaged medicinal plant and bottle herbal distillate samples. MethodsThree-hundred different powdered packaged medicinal plant and bottle herbal distillate samples produced in traditional conditions were collected and examined by the culture method. Phenotypic and genotypic patterns of antibiotic resistance of S. aureus isolates were examined using disk diffusion and PCR techniques. ResultsThirty out of three-hundred (10%) powdered packaged medicinal plant and bottle herbal distillate samples were contaminated with S. aureus. The prevalence of S. aureus amongst the powdered packaged medicinal plant and bottle herbal distillate samples were 8.33% and 11.11%, respectively. A. citrodora (10%) and R. damascene (10%) powdered packed medicinal plants and A. maurorum (16.66%) bottle herbal distillate had the highest contamination rate with S. aureus. S. aureus isolates harbored the highest prevalence of resistance toward penicillin (93.33%), tetracycline (90%), gentamicin (86.66%), erythromycin (70%), trimethoprim-sulfamethoxazole (63.33%) and ciprofloxacin (53.33%). Totally, 13.33% of the S. aureus isolates harbored resistance toward more than 7 antibiotic agents. blaZ (63.33%), tetK (60%), ermA (46.66%), msrA (43.33%), aacA-D (43.33%), and mecA (43.33%) were the most frequent antibiotic resistance genes. ConclusionsPowdered packaged medicinal plant and bottle herbal distillate samples may be sources of multidrug resistant-S. aureus, which poses a hygienic threat concerning the consumption of these therapeutic options in Iran. Nevertheless, further research is compulsory to understand other epidemiological features of S. aureus in powdered packaged medicinal plant and bottle herbal distillate samples.
The Impact of Non-compliance to Standardized Risk-adjusted Protocol in Non-Muscle Invasive Bladder Cancer on Recurrence, Progression and Mortality: Lessons to Learn in the Era of COVID-19
Authors: Abushamma Faris , Khayyat Zain , Soroghle Aya , Zyoud Sa’ed H. , Jaradat Ahmad , Akkawi Maha , Aburass Hanood , Qaddumi Iyad K. K. , Odeh Razan , Salameh Husam , Albuheissi Salah 
Published: December 2020

Abstract
BackgroundNon-Muscle Invasive Bladder Cancer (NMIBC) is potentially curable or a controllable disease if strict adherence to surveillance protocol is followed. Management and surveillance of NMIBC begin at the time of diagnosis up to few years thereafter based on the risk group category. There is scanty data in the literature evaluating the impact of non-compliance to surveillance protocol on progression, recurrence, and mortality rate. We do believe that this data will add to the literature especially during the COVID-19 pandemic which affects and delays daily elective surgeries. MethodsA retrospective study of two hundred bladder biopsy and resection between 2012-2017. Eighty-eight patients with minimal 3 years follow up data were included. Patients were divided into 2 groups based on their compliance with the cystoscopy follow up as recommended by the European guidelines. We compared the cystoscopy compliant group to the non-compliant group in view of recurrence, progression, and mortality. In addition, missing variable items during surveillance are calculated in a new scoring model to predict the adverse outcome. ResultsRecurrence rate (RR), progression rate (PR), metastasis rate (MsR) and mortality rate (MR) are significantly higher in non-compliant group, RR: (92.6%) (P<0.001), PR: (54.1%) (P<0.001), MsR: (37.7%) (P<0.001), MR: (23.5%) (P= 0.002) respectively. In subgroup analysis, intermediate and high-risk groups have a PR rate of zero in the compliant group while it is 100% (P<0.001) and 56.4% (P=0.001) in the non-compliant group respectively. Kaplan Meier (KM) graph shows that compliant patients were more likely to be better than non-compliant. ConclusionsNoncompliance to a standardized surveillance protocol in NMIBC is associated statistically and clinically with adverse outcomes in comparison to a compliant group which mandates strict adherence to surveillance guidelines to improve outcomes in NMIBC.
An Effective Gene-Based Rare Variant Association Analysis Pipeline for Case-Control Studies of Disease
Authors: Wen Canhong , Li Ruijia , Cai Jiahui , Tan Haizhu 
Published: December 2020

Abstract
BackgroundIn complex disease studies, genome-wide association study (GWAS) has been successfully used for identifying associated genetic risk loci. In fact, only a small fraction of the apparent heritability can be explained by common variants. Because research efforts have largely focused on common genetic variants, the missing heritability could be mostly due to rare genetic variants. Substantial research efforts have been devoted to developing software for genotype imputation and designing variant binning strategies and statistical methods for rare variant association testing of datasets on GWAS chips. However, few systematic pipelines have been proposed to identify rare disease-related genes. ResultsWe present EGRVA, an Effective Gene-based Rare Variant Association analysis pipeline for genotype imputation, quality control, gene-based functional annotation, statistical analysis, and bioinformatics analysis of identified genes. As a complementary pipeline for rare variant analysis on GWAS chips, EGRVA is relatively straightforward and cost-efficient. Furthermore, we tested the EGRVA pipeline with the preterm birth (PTB) dataset from the GPN-PBR. We focused on the 6 genes identified by EGRVA: FLG, HRNR, PMS1, ATM, OR2AG1 and SLC22A25. We also explored the underlying biological interpretation of these potentially significant genes. ConclusionsAs a complementary pipeline for rare variant analysis on GWAS chips, EGRVA is relatively straightforward and costefficient. The application of the pipeline will contribute to the support of rare variants to explain the missing heritability by effectively discovering genes related to disease.
A Novel Nomogram Containing Acute Radiation Esophagitis Predicting Radiation Pneumonitis in Thoracic Cancer Receiving Radiotherapy
Authors: Tang Wenjie , Li Xiaolin , Yu Haining , Yin Xiaoyang , Zou Bing , Zhang Tingting , Chen Jinlong , Sun Xindong , Liu Naifu , Yu Jinming , Xie Peng 
Published: December 2020

Abstract
BackgroundRadiation-induced pneumonitis (RP) is a non-negligible and sometimes life-threatening complication in patients with thoracic radiation. We initially aimed to ascertain the predict value of acute radiation-induced esophagitis (SARE, grade≥2) to symptomatic RP (SRP, grade≥2) among thoracic cancer patients receiving radiotherapy. Based on that, we also established a novel nomogram model to provide individualized risk assessment for SRP.MethodsPatients with thoracic cancer who were treated with thoracic radiation from Jan 2018 to Jan 2019 in Shandong Cancer Hospital and Institute were enrolled prospectively. All patients were followed up during and after radiotherapy (RT) to observe the appearance of esophagitis and pneumonitis. Variables were analyzed by univariate and multivariate analysis using the logistic regression model, and a nomogram model was established to predict SRP by "R" version 3.6.0.ResultsA total of 123 patients were enrolled (64 esophageal cancer, 57 lung cancer and 2 mediastinal cancer) in this study prospectively. RP grades of 0, 1, 2, 3, 4 and 5 occurred in 29, 57, 31, 0, 3 and 3 patients, respectively. SRP appeared in 37 patients (30.1%). In univariate analysis, SARE was shown to be a significant predictive factor for SRP (P < 0.001), with the sensitivity 91.9% and the negative predictive value 93.5%. The incidence of SRP in different grades of ARE were as follows: Grade 0-1: 6.5%; Grade 2: 36.9%; Grade 3: 80.0%; Grade 4: 100%. Besides that, the dosimetric factors considering total lung mean dose, total lung V5, V20, ipsilateral lung mean dose, ipsilateral lung V5, and mean esophagus dose were correlated with SRP (all P < 0.005) by univariate analysis. The incidence of SRP was significantly higher in patients whose symptoms of RP appeared early. SARE (HR 34.408, P = 0.001), mean esophagus dose and ipsilateral mean lung dose were still significant in multivariate analysis, and they were included to build a predictive nomogram model for SRP.Conclusions﻿SARE was an easy index that can reflect patients’ radiosensitivity visually, which could be an applicable predictor for SRP in patients receiving thoracic radiation. And the nomogram could assist in accurate prediction to SRP in clinic.
Targeting ACLY Attenuates Tumor Growth and Acquired Cisplatin Resistance in Ovarian Cancer by Inhibiting PI3K/AKT Pathway and Activating AMPK/ROS Pathway
Authors: Wei Xuan , Shi Juanjuan , Lin Qianhan , Ma Xiaoxue , Pang Yingxin , Mao Hongluan , Li Rui , Lu Wei , Wang Yu , Liu Peishu 
Published: December 2020

Abstract
Background: Ovarian cancer is the most lethal female genital malignancy. Though cisplatin is still the first-line chemotherapy to treat ovarian cancer patients with debulking surgeries, its efficacy is limited due to the high-incidence of cisplatin resistance. ATP citrate lyase (ACLY) has been proved to be a key metabolic enzyme and was related to poor prognosis in various cancer, including ovarian cancer. Nevertheless, there has not been any research elucidating the relationship between ACLY and cisplatin resistance and the mechanism of how it works.Methods: Survival analysis was mainly carried out on the website. Bioinformatic analysis was performed in R/R studio. Proliferative activity was measured by MTT assay and colony formation assay. Cell cycle and apoptosis analysis were performed by flow cytometry. Acquired cisplatin resistant cell line A2780/CDDP was generated from A2780 by exposing to gradually elevated concentration of cisplatin. MTT assay was used to calculate IC50 of cisplatin. Xenograft tumor assay was used test cell proliferation in vivo.Results: Higher expression of ACLY was found in ovarian cancer tissue and related to poor prognosis. Knockdown of ACLY in A2780, SKOV3 and HEY cells inhibited cell proliferation, caused cell cycle arrest by modulating P16/CDK4/CCDN1 pathway and induced apoptosis probably by inhibiting p-AKT activity. Bioinformatic analysis of GSE15709 dataset revealed upregulation of ACLY and activation of PI3K/AKT pathway in acquired cisplatin resistant cells, in line with the results of A2780/CDDP cells generated by us. Knockdown of ACLY could alleviate cisplatin resistance and work synergistically with cisplatin treatment in inducing apoptosis in A2780/CDDP cells, by inhibiting PI3K/AKT pathway and activating AMPK/ROS pathway. ACLY specific inhibitor SB-204990 also showed the same effect. In A2780/CDDP cells, AKT overexpression could destroy cisplatin re-sensitization caused by ACLY knockdown. Conclusions: Knockdown of ACLY attenuated cisplatin resistance by inhibiting PI3K/AKT pathway and activating AMPK/ROS pathway. These findings suggested that combination of ACLY inhibition and cisplatin could be an effective strategy for overcoming cisplatin resistance in ovarian cancer.