bluuebunny/crossref_metadata_2025_split huggingface dataset:
Triple-Negative Breast Cancer (TNBC) Cell Metastasis is Controlled by the Opposing Actions of 5alpha-dihydroprogesterone (5alphap) and 3alpha-dihydroprogesterone (3alphahp) on Expression of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases
Authors: Wiebe John Peter , Jarvis Jordan , Kwok Arthur 
Published: October 2020

Abstract
BackgroundTriple receptor-negative breast cancers (TNBC) comprise up to 20% of all breast cancers and are the most aggressive mammary cancer subtype, marked by early-onset metastasis, high tumor recurrence rate, and low overall survival. Because TNBC cells lack expression of the estrogen receptor (ER), progesterone receptor (PR) and excess human epidermal growth factor receptor 2 (HER2), there have been no hormone-based explanations and therapeutics for TNBC. Our previous studies had shown that the endogenously produced hormones, 5αdihydroprogesterone (5αP) and 3α-dihydroprogesterone (3αHP), respectively, stimulate and inhibit TNBC cell proliferation and primary tumor development. Here we examined the role of 5αP and 3αHP in controlling metastasis of TNBC (MDA-MB-231)human breast cells. The objectives were to determine the effects of 5αP and 3αHP on TNBC cell (a) adhesion, migration and invasion and (b) expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs).MethodsMDA-MB-231 human breast cells were incubated in medium without (control) or with 5αP or 3αHP. Effects on adhesion were examined by previously validated detachment assays. Effects on migration and invasion were measured by transwell assays employing modified Boyden chambers. Effects on expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 were determined by reverse transcription polymerase chain reaction (RT-PCR).Results5αP stimulated, whereas 3αHP suppressed, TNBC cell detachment, migration and invasion. 5αP stimulated expression of MMP-2 and MMP-9, and inhibited expression of TIMP-1 and TIMP-2, whereas 3αHP inhibited expression of MMPs and stimulated expression of TIMPS.ConclusionsHere we show for the first time that 5αP stimulates and 3αHP suppresses the key elements of metastasis (adhesion, migration, invasion) in TNBC cells, and that these opposing actions correlate with the opposing effects of these two hormones on MMP and TIMP expression. The results indicate that the relative concentrations of the cancer-promoter hormone (5αP) and the cancer-suppressor hormone (3αHP) in the breast microenvironment control TNBC cell metastasis, and suggest that blocking 5αP synthesis and increasing 3αHP concentrations in the breast microenvironment could provide the first hormone-based therapeutic regimen to arrest TNBC progression and metastasis.
Long-term Survival Outcomes of Invasive Micropapillary Carcinoma of the Breast: A Population-based Study
Authors: Zhang Xiao , Lin Yufeng , Su Yingying , Yang Qingmo 
Published: October 2020

Abstract
Background: Whether or not invasive micropapillary carcinoma(IMPC) histology is an independent prognostic factor for breast cancer remains controversial. Moreover, the relationship between different molecular subtypes and survival outcomes of IMPC and invasive ductal carcinoma (IDC) is still unknown.Methods: Using the SEER database to identify breast cancer patients, we retrospectively analyzed 959 IMPC and 174591 IDC cases diagnosed between 2010-2016 with non-metastatic diseases that underwent surgery. Specifically, we compared long-term outcomes of breast cancer-specific survival (BCSS) and overall survival (OS).Results: Relative to IDC patients, IMPC patients were younger at diagnosis and had more moderate and poorly differentiated tumors (93.2% vs. 78.5%), more T3 and T4 tumors (11.0% vs. 6.9%), a higher percentage of nodal involvement (48.9% vs. 30.9%) and AJCC stage III patients (11.9% vs. 6.9%), and presented a higher proportion of HR positivity (91.2% vs. 82.3%) and HER2 positivity (22.3% vs. 16.9%). IMPC had a better BCSS (P=0.039) but showed no significant difference in OS (P=0.095) compared with IDC. In multivariate Cox analysis, IMPC histologic type was an independent favorable prognostic factor for both BCSS (HR=0.509, P=0.002, 95%CI: 0.335-0.775) and OS (HR=0.637, P=0.003, 95%CI: 0.475-0.854). After the case-control matched analysis using the propensity score matching method, IMPC still had a better BCSS (P=0.001); however, we observed no significant difference in OS (P =0.385). While different molecular subtypes have different impacts on survival outcomes, no significant differences were observed in BCSS and OS between IMPC and IDC in relation to Luminal B, HER2-enriched, and Triple-negative subtypes. However, in relation to the Luminal A subtype, IMPC had better BCSS (HR= 0.399, P=0.001, 95%CI: 0.226−0.703) and OS (HR=0.508, P=0.001, 95%CI: 0.345−0.746). In the case-control cohort, IMPC still had a better BCSS (HR= 0.423, P=0.005, 95%CI: 0.233−0.770), but no significantly difference was observed in OS (HR=0.767, P=0.22, 95%CI: 0.502−1.172) in Luminal A subtype.Conclusion: Relative to IDC, IMPC presents better long-term survival outcomes, and the survival benefits are confined to the Luminal A subtype.
Prognostic nomogram for penile cancer, an analysis based on SEER database
Authors: Chen Yon-Bo , Gao Liang , Tang Liang-You , Guo Jiang , Tian Yu-Chang , You PingHong 
Published: October 2020

Abstract
BackgroundWe aimed to establish a prognostic nomogram for Penile Cancer (PC) patients based on the Surveillance, Epidemiology, and End Results Program (SEER) database.MethodsData of 1694 patients between 2010 and 2015 were downloaded and extracted from the SEER database. Then, they were randomly divided into the development group (70%) and the verification group (30%). Following, the univariate and multivariate Cox proportional hazards regression was respectively used to explore the possible risk factors of PC. Factors which significantly related to the overall survival (OS) were used to establish the nomogram. Further, the concordance index (C-index), receiver operating characteristic curve (ROC) and calibration curve were used to assess the nomogram, respectively. An internal validation was carried out to test the accuracy and effectiveness of nomogram. Finally, the Kaplan-Meier calculation was used to predict the further survival status of these patients.ResultsMultivariate Cox proportional hazards regression demonstrated that the independent prognostic risk factors associated with PC were age, stage T, N and M, and grade, with a moderate c-index of 0.732 [95% confidence interval (CI), 0.706-0.757] in development group and 0.743 (95% CI, 0.703-0.782) in verification group. Meanwhile, the areas under the ROC (AUC) of 3-year and 5-year survival were 0.739 and 0.727, respectively. The survival calibration curves of 3-year and 5-year brought out a high consistency. ConclusionOur study obtained a satisfactory nomogram to reveal the survival of PC patients, which could be helpful for clinicians to assess the situation of PC patients and to implement the further treatment.
The Effectiveness of Parent Training Interventions in Autism Spectrum Disorder: A Systematic Review
Authors: Tabatabaei Seyed Hasan , Shahrokhi Hassan , Gholipour Kamal , Izadi Shabnam , Rezapour Ramin , Azami-Aghdash Saber 
Published: October 2020

Abstract
Background: The role of parents in taking care of children with Autism Spectrum Disorder (ASD) is critical. This systematic review study aimed to investigate the effect of parents-based training interventions on taking care of children with ASD.Method: All relevant studies were searched through some electronic databases such as PubMed, Scopus, Google Scholar, Cochrane Library, Science Direct, Web of knowledge, and also via hand searching in relevant journals, checking the reference list of articles, expert contact, and grey literature from 1 January 2000 to 30 February 2020. Result: Eventually, 53 articles were considered. In total, 1758 parents of children with ASD participated in these studies that 49 studies were conducted in high-income countries, 19 studies in the home, 25 studies in the training centers.14 studies carried out only in training way, 39 studies in training along with practices and assignments, 30 individual interventions, 21 interventions in the group. Most studies had a range of 10 to 30 sessions in a 60 to 120-minute period. Also, the effectiveness of interventions was studied in both parents and children groups. Conclusion: According to the included studies, parents-based training interventions have significant impacts on parents and their children's behavior.
MicroRNA-221-3p promotes proliferation and invasion in non-small cell lung cancer via targeting Axin2 to regulate Wnt/β-catenin signaling pathway
Authors: Zheng Jiangnan , Dong Lingyun , Hu Xiaoyun , Xiao Ying , Wu Qiaozhen , Wang Yang , Zhu Yehan 
Published: October 2020

Abstract
ObjectiveThe mortality rate of lung cancer ranks first in malignant tumors. Among them, non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancer patients. In this study, we explore part of the mechanism of development and progression of NSCLC.Methods/ ResultsFirstly, there was an increase in microRNA-221-3p (miR-221-3p) expression and a decrease in Axin2 expression in NSCLC tissues using real-time reverse transcription polymerase chain reaction. Further studies showed that miR-221-3p inhibited the expression of Axin2, which negatively regulated the Wnt signaling pathway. With the method of inhibiting and overexpressing the expression of miR-221-3p and/or Axin2 respectively in NSCLC cell lines A549 and H1975, we found that inhibiting the expression of miR-221-3p leaded to a decrease in cell proliferation, migration and invasion, just like the results of overexpressing Axin2. Relatively speaking, overexpression of miR-221-3P in NSCLC cell lines showed the increase of proliferation as well as the decrease of apoptosis. Thus, we knew that miR-221-3p promoted the migration and invasion of NSCLC cells in vitro. What’s more, according to western blot and EdU assay, we demonstrated that overexpression of miR-221-3p inhibited the expression of Axin2 and subsequently activate classical Wnt/β-catenin signaling pathway. At last, a series of methods were used to identify that miR-221-3p inhibited Axin2 expression, increased cell proliferation, invasion and migration, and decreased cell apoptosis.ConclusionOur results suggest that miR-221-3p inhibits the expression of Axin2 and indirectly activates the typical Wnt/β-catenin signaling pathway, thus promoting tumor proliferation and invasion in NSCLC.
Dynamic Impact of Development and Energy Consumption Pattern on Environmental Quality: A Case Study of Selected Populous Asian Countries
Authors: Afzal Hafiz Mohammad , Rehman Hafeez Ur , Asim Hafiz , Akhtar Muhammad Javed 
Published: October 2020

Abstract
The present study aims to examine the long-run and short-run effects of economic development, energy consumption pattern, trade openness and urbanization on environmental quality in ten Asian most populous economies. The analysis examines panel data from 1988 to 2018 by employing an Autoregressive Distributed Lag (ARDL) approach. The results indicate that the struggles to raise development are increasing the CO 2 emissions in these emerging populous countries. Moreover, the utilization of non-renewable energy sources (gas, coal, oil) is associated with high carbon emissions affecting environmental quality adversely and worsening the atmosphere at the zonal level too. Furthermore, the empirical findings highlight that urbanization and trade openness partake to the reduction of CO 2 emission and hence are considered environmental friendly. Finally, the government should formulate the strategies which help to reduce the use of non-renewable energy sources and promote the consumption of efficient gas energy source to raise development and better environmental quality in populous countries of Asia and hence the strategies will be helpful for the comfort and happiness of this part of the emerging region.
Identification of a Novel Epithelial-Mesenchymal Transition Gene Signature Regulated by KEAP1-NRF2 Pathway in Esophageal Carcinoma
Authors: Elshaer Mohamed , Hammad Ahmed , Wang Xiu Jun , Tang Xiuwen 
Published: October 2020

Abstract
BackgroundKEAP1-NRF2 pathway alterations were identified in many cancers including, esophageal cancer (ESCA). Identifying biomarkers that are associated with mutations in this pathway will aid in defining this cancer subset; and hence in supporting precision and personalized medicine. MethodsIn this study, 182 tumor samples from the Cancer Genome Atlas (TCGA)-ESCA RNA-Seq V2 level 3 data were segregated into two groups KEAP1-NRF2-mutated (22) and wild-type (160).The two groups were subjected to differential gene expression analysis, and we performed Gene Set Enrichment Analysis (GSEA) to determine all significantly affected biological pathways. Then, the enriched gene set was integrated with the differentially expressed genes (DEGs) to identify a gene signature regulated by the KEAP1-NRF2 pathway in ESCA. Furthermore, we validated the gene signature using mRNA expression data of ESCA cell lines provided by the Cancer Cell Line Encyclopedia (CCLE). The identified signature was tested in 3 independent ESCA datasets to assess its prognostic value.ResultsWe identified 11 epithelial-mesenchymal transition (EMT) genes regulated by the KEAP1-NRF2 pathway in ESCA patients. Five of the 11 genes showed significant over-expression in KEAP1-NRF2-mutated ESCA cell lines. In addition, the over-expression of these five genes was significantly associated with poor survival in 3 independent ESCA datasets, including the TCGA-ESCA dataset.ConclusionAltogether, we identified a novel EMT 5-gene signature regulated by the KEAP1-NRF2 axis and this signature is strongly associated with metastasis and drug resistance in ESCA. These 5-genes are potential biomarkers and therapeutic targets for ESCA patients in whom the KEAP1-NRF2 pathway is altered.
Effect of Cross-Linked Enzyme Aggregates Strategy on Characterization of sn-1,3 Extracellular Lipase from Aspergillus Niger GZUF36
Authors: Zhu Ruonan , Chen Cuicui , Xing Shuqi , Cai Yangyang , Li Cuiqin , Zeng Xuefeng , He Laping 
Published: October 2020

Abstract
Background: A novel Aspergillus. niger strain GZUF36 with two high sn-1,3 position selectivity of lipases, including an intracellular lipase and an extracellular one was selected from oil-rich soil in our previous work. The sn-1,3 extracellular lipase from Aspergillus niger GZUF36 (EXANL1) has important potential applications. However, the structure and properties of this lipase need further study for its better application, the immobilization of enzyme is an effective method to study its structural properties and obtain the best catalytic properties. Cross-linked enzyme aggregates (CLEAs) have been widely used in carrier-free immobilization technologies because of their low cost and fast preparation. To this end, it is necessary to investigate the effect of CLEAs strategy on the characteristics, secondary structure, and positional selectivity of EXANL1 before and after immobilization.Results: The CLEAs of purified EXANL1 (CLEA-EXANL1) was achieved optimum activity recovery (100.3±1.1%) with 80% tert-butanol as the precipitant, a glutaraldehyde (GA) concentration of 30 mM, a GA treatment time of 1.5 h, and a centrifugal speed of 6000 g. CLEA-EXANL1 exhibited a broader optimum pH range (4–6) compared with free EXANL1 (6.5). CLEA-EXANL1 presented optimum activity at 40 °C, which was 5 °C higher than that of free EXANL1. CLEAs strategy decreased the maximum reaction rate and increased the Michaelis–Menten constant of EXANL1 when olive oil emulsion was used as a substrate. Moreover, after 30 days, free EXANL1 lost more than 80.0% of its activity, whereas CLEA-EXANL1 retained more than 90.0% of its activity. CLEAs strategy improved the tolerance of EXANL1 in polar organic solvents. Fourier transform infrared spectroscopy results showed that the CLEAs technique increased the content of the β-sheets and β-turns of EXANL1 and reduced α-helixes and irregular crimp contents. CLEAs strategy did not change the sn-1,3 selectivity of EXANL1.Conclusion: The effect of CLEAs technology on catalytic properties, structure, selectivity and other characteristics of the EXANL1 was comprehensively explored, which laid a foundation for its subsequent rational transformation and industrial application.
Simple Indicators of Energy Malnutrition in Patients With Chronic Liver Diseases
Authors: Takada Hitomi , Amemiya Fumitake , Yasumura Tomoki , Yoda Hiroki , Okuwaki Tetsuya , Tanaka Keisuke , Kadokura Makoto , Enomoto Nobuyuki 
Published: October 2020

Abstract
Objective: Protein–energy malnutrition (PEM) is an important prognostic factor in patients with cirrhosis. Energy malnutrition (EM) is defined by the Japanese Society of Gastroenterology Guidelines for cirrhosis as a non-protein respiratory quotient <0.85, a % arm circumference (%AC) <95%, or a free fatty acid (FFA) value >660 μEq/L. The parameters associated with EM are difficult to measure in all patients. In this study, we evaluated simple indicators of EM.Methods: This retrospective study included 295 patients with chronic liver diseases (CLDs) in whom serum FFA values or %AC were measured at the Department of Gastroenterology at the Municipal Hospital of Kofu. We examined the characteristics of the patients with EM. Results: EM was observed in 36% of patients with CLDs without a late-evening snack (LES). The frequency of EM was high in patients with Child–Pugh grade B or C, γ-GTP level ≥100 U/ml, AST level ≥27 IU/l, and ALT level ≥27 IU/l in males, and Child–Pugh grade B or C, γ-GTP ≥84 U/ml, AST ≥24 IU/l, and ALT ≥28IU/l in females. Among the three indicators of Child–Pugh grade B or C, increased γ-GTP levels, and increased transaminase values, EM was observed in 16%, 35%, 59%, and 57% of patients who were positive for 0, 1, 2, or 3 of the indicators. The frequency of EM in patients with Child-Pugh grade A was high for increased γ-GTP, AST, and ALT levels. Among the two indicators of increased γ-GTP, and transaminase levels, 16%, 32%, and 67% of patients were positive for 0, 1, or 2 of the indicators.Conclusion: Child-Pugh grade, transaminase values, and γ-GTP levels were useful indicators of EM in patients with CLDs. We should evaluate positively the presence of EM in cases with poor liver function, high transaminase concentrations, or high γ-GTP levels.
Application of ASTLOF Scoring System in the Treatment of Acute Symptomatic Thoracolumbar Compression Fractures
Authors: Li Qing-Da , Yang Jun-Song , Jiang Chao , Ma Yi-Fan , Tian Xin , Yang Ming-Yi , Huang Wang-Li , Tuo Yuan , Hao Ding-Jun 
Published: October 2020

Abstract
Background: Osteoporotic vertebral compression fracture (OVCF) is a common injury in the elderly, often caused by low-energy injuries. Improper treatment will not only affect the stability and balance of the spine, but in severe cases will lead to neurological damage and increase the risk of death. This retrospective study aims to explore the principles of treatment of patients with the assessment system of thoracolumbar osteoporotic fracture (ASTLOF) in acute symptomatic thoracolumbar compression fractures when the ASTLOF score = 4 points.Methods: The clinical data of patients with acute symptomatic thoracolumbar compression fractures admitted from February 2018 to February 2020 were retrospectively analyzed. Each patient was evaluated according to the ASTLOF scoring system, and patients with ASTLOF score = 4 were selected, a total of 108 patients. According to different treatment methods, they were divided into 32 cases in the non-surgical treatment (NST) group and 76 cases in the surgical treatment (ST)group. The visual analog score (VAS), Oswestry disability index (ODI), the recovery of injured vertebral body height, and the incidence of adjacent segment fractures were used for comprehensive evaluation.Results: During the follow-up, the VAS score and ODI score showed that the early pain relief and functional improvement of the surgical treatment group were better than those of the conservative treatment group (P<0.05); the Cobb angle of the surgical treatment group was 3 months and 6 months after the operation, and the vertebral body was injured. The degree of improvement of margin height was better than that of the conservative treatment group (all P<0.05); in the surgical treatment group, 6 cases of adjacent vertebral fractures occurred after surgery, accounting for 7.89%, and 2 cases of the conservative treatment group had adjacent vertebral fractures, accounting for 6.25% There was no statistically significant difference between the two groups (P>0.05).Conclusions: When the ASTLOF scoring system is used in the treatment of acute symptomatic thoracolumbar compression fractures, patients with ASTLOF score =4 should be treated with surgery in time, which can relieve pain early and quickly, perform functional exercises as soon as possible, and reduce complications related to long-term bed rest. Whether it increases the risk of adjacent vertebral fractures requires long-term follow-up studies in a large number of cases.
Further Evaluation of the Mother-to-Child Transmission Potential of SARS-CoV-2 Infection During Pregnancy: A Retrospective Study
Authors: Yu Xuechen , Chen Huijun , Luo Fan , Guo Juanjuan , Qiao Yuan , Zhang Wei , Li Jiafu , Zhao Dongchi , Xu Dan , Gong Qing , Yang Lingyun , Yang Pu , Cao Yuming , Wen Xue , Hou Wei , Yang Huixia , Zhang Yuanzhen 
Published: October 2020

Abstract
Background. This study aimed to comprehensively evaluate the clinical characteristics of COVID-19 in perinatal period, and systematically assess the mother-to-child transmission potential of SARS-CoV-2Methods. We retrospectively analyzed the data of 23 pregnant patients in late pregnancy. Clinical specimens, including maternal and neonatal throat swabs, vaginal secretions, placenta tissues, and breast milk, were collected for the nucleic acid test of the virus. Pregnancy outcomes and neonatal results were also analyzed.Results. Overall, 10 patients (43.5%) had no symptoms and were found by routine chest CT. Complications appeared after COVID-19 onset included PROM (17.4%) and fetal distress (4.3%). Typical signs of viral pneumonia were recorded in chest CT of all patients. No patients developed severe pneumonia or died of COVID-19. All of 25 neonates were born alive. No severe asphyxia or neonatal death was observed. Although three neonates were tested transiently suspected positive for SARS-CoV-2 after being transferred to neonatology department, no newborns developed COVID-19. Out of various clinical specimens tested, only a rectal swab sample from one pregnant patient was tested positive for SARS-CoV-2, while all the other specimens including first sample of newborn throat swabs were negative. Pathological examination found no obvious chorioamnionitis or clear virus inclusion body in placenta, and ACE2 (angiotension-converting enzyme 2) was expressed at a moderate level.Conclusions. As in the general population of COVID-19, asymptomatic patients were present in pregnant women. There is no confirmatory evidence for mother-to-child transmission in COVID-19 patients with late pregnancy.