bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mid-term Outcome Of Surgical Treatment In Pediatric Patients With Ebstein's Anomaly: A Single-center Cohort Study.
Authors: Li Jia-chen , Jiang Xian-chao , Zhang Si-meng , Liu Jin-yang , Zhang Ya-juan , Yan Jun , Li Shou-jun , Wang Qiang 
Published: July 2020

Abstract
Background: Ebstein’s anomaly is a malformation of the tricuspid valve and myopathy of the right ventricle. Surgery is now the main treatment for the defect. To summarize our surgical results and experience based on patients with Ebstein’s anomaly who were under 7 years of age and treated with different surgical treatments.Materials and Methods: From January 2010 to December 2019, 80 patients under 7 years old who were diagnosed of Ebstein’s anomaly and underwent different surgical treatments were consecutively enrolled and followed up in detail. Results: The median age of the 80 patients at the time of surgery was 3.63 years. Sixty-four (80.00%) patients underwent biventricular repair while 13 (16.25%) underwent 1.5-ventricle repair. With the median follow-up 27.50 months, the long-term survival of the total cohort, 1.5-ventricular repair and biventricular repair was 82.35%, 91.67% and 100%, respectively. The long-term freedom from reoperation rate was 97.50%, 92.31% and 98.44%, respectively. Mild, moderate and severe TR before surgery occurred in 6 (7.50%), 18 (22.50%) and 56 (70.00%), respectively. The early outcomes of 78 patients were 65 (83.33%), 11 (14.11%) and 2 (2.56%); the mid-term outcomes of 72 patients were 49 (68.06%), 19 (26.38%) and 4 (5.56%). Both early and long-term valve regurgitation were significantly decreased (p< 0.001) compared with preoperative condition. No more severe regurgitation occurred (p=0.404), though some early mild regurgitation became acceptable moderate regurgitation during long-term follow-up (p=0.036). Compared with Carpentier procedure, cone procedure had better long-term effect, while the effect of whole-valve technique needed more operation and long-term follow-up.Conclusion: The reoperation rate and mid-term mortality of surgical treatment for Ebstein’s anomaly were both low, tricuspid regurgitation was significantly improved during mid-term follow up. Cone procedure had the best mid-term effect among anatomic repair.
Intensity-modulated radiation therapy versus three-dimensional conformal radiotherapy in head and neck squamous cell carcinoma: long-term and mature outcomes of a prospective randomized trial
Authors: Gupta Tejpal , Sinha Shwetabh , Laskar Sarbani Ghosh , Budrukkar Ashwini , Mummudi Naveen , Swain Monali , Phurailatpam Reena , Prabhash Kumar , Agarwal Jai Prakash 
Published: July 2020

Abstract
Background: To compare long-term disease-related outcomes and late radiation morbidity between intensity-modulated radiation therapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) in head and neck squamous cell carcinoma (HNSCC) in the setting of a prospective randomized controlled trial.Methods: Previously untreated patients with early to moderately advanced non-metastatic squamous carcinoma of the oropharynx, larynx, or hypopharynx (T1-T3, N0-N2b, M0) were randomly assigned to either IMRT or 3D-CRT after written informed consent. Patients were treated with 6MV photons to a total dose of 70Gy/35 fractions over 7 weeks (3D-CRT) or 66Gy/30 fractions over 6 weeks (IMRT). A sample size of 60 patients was estimated to demonstrate 35% absolute difference in the incidence of ≥grade 2 acute xerostomia between the two arms. All time-to-event outcomes were calculated from date of randomization till the defined event using the product-limit method of Kaplan-Meier. Results: At a median follow-up of 140 months for surviving patients, 10-year Kaplan-Meier estimates of loco-regional failure free-survival (LRFFS); final loco-regional control (LRC) including surgical salvage; and overall survival (OS) with 95% confidence interval (95%CI) were 72% (95%CI: 59.4-84.6%); 79.7% (95%CI: 68.7-90.7%); and 50.3% (95%CI: 37.1-63.5%) respectively. There were no significant differences in 10-year disease-related outcomes between 3D-CRT and IMRT for LRRFS [75.7% (95%CI: 58.1-93.3%) vs 68.7% (95%CI: 51.1-86.3%), p=0.56]; final LRC [83% (95%CI: 67.2-98.8%) vs 76.9% (95%CI: 61.5-92.3%), p=0.50]; or OS [44.9% (95%CI: 25.7-64.1%) vs 55.0% (95%CI: 37-73%), p=0.49]. Significantly lesser proportion of patients in the IMRT arm experienced ≥grade 2 late xerostomia and subcutaneous fibrosis at all time-points. However, at longer follow-up, lesser number of patients remained evaluable for late radiation toxicity reducing statistical power and precision. Conclusions: IMRT provides a clinically meaningful and sustained reduction in the incidence of moderate to severe xerostomia and subcutaneous fibrosis compared to 3D-CRT without compromising disease-related outcomes in long-term survivors of non-nasopharyngeal HNSCC. Trial registration: Registered at the Clinical Trials Registry of India (CTRI/2008/091/000045) (Retrospectively registered)
Whole-brain irradiation differentially modifies neurotransmitters levels and receptors in the hypothalamus and the prefrontal cortex
Authors: Franco-Pérez Javier , Montes Sergio , Sanchez-Hernández Josué , Ballesteros-Zebadúa Paola 
Published: July 2020

Abstract
Background: Whole-brain radiotherapy is a primary treatment for brain tumors and brain metastasis, but it also induces long-term undesired effects. Since cognitive impairment can occur, research on the etiology of secondary effects has focused on the hippocampus. Often overlooked, the hypothalamus controls critical homeostatic functions, some of which are also susceptible after whole-brain radiotherapy. Therefore, using whole-brain irradiation in a rat model, we measured neurotransmitters and receptors in the hypothalamus. The prefrontal cortex and brainstem were also analyzed since they are both highly connected to the hypothalamus and its regulatory processes. Methods: Male Wistar rats were exposed to whole-brain irradiation with 11 Gy (BED= 72Gy). After one month, we evaluated changes in gamma-aminobutyric acid (GABA), glycine, taurine, aspartate, glutamate, glutamine, in the hypothalamus, prefrontal cortex, and brainstem according to an HPLC method. Ratios of Glutamate/GABA and Glutamine/Glutamate were calculated. Through Western Blott analysis, we measured the relative expression of GABAa and GABAb receptors, and NR1 and NR2A subunits of NMDA receptors. Changes were analyzed comparing results with sham controls using the non-parametric Mann-Whitney U test (p<0.05). Results: Whole-brain irradiation with 11Gy induced significantly lower levels of GABA, glycine, taurine, aspartate, and GABAa receptor in the hypothalamus, one month after exposure. Also, in the hypothalamus, a higher Glutamate/GABA ratio was found after irradiation. In the prefrontal cortex, WBI induced significantly increased levels of glutamine and glutamate, Glutamine/Glutamate ratio, and increased expression of both GABAa receptor and NMDA receptor NR1 subunit. The brainstem showed no statistically significant changes after irradiation. Conclusions: Our findings confirm that whole-brain irradiation can affect rat brain regions differently and opens new avenues for study. After one month, WBI decreases inhibitory neurotransmission in the hypothalamus and, conversely, increases excitatory neurotransmission in the prefrontal cortex. Increments in Glutamate/GABA in the hypothalamus and Glutamine/Glutamate in the frontal cortex both indicate a modified neurochemical balance. Found changes could be related to several reported radiotherapy secondary effects, suggesting new prospects for therapeutic targets.
TRIM8 Inhibits Breast Cancer Proliferation by Regulating Estrogen Signaling
Authors: Tian Zelin , Tang Jianing , Liao Xing , Yang Qian , Wu Yumin , Wu Gaosong 
Published: July 2020

Abstract
Background: Breast cancer (BC) ranks first in female malignancies wordwide, 70% of which are estrogen receptor alpha (ERα) positive. Endocrine treatment, such as tamoxifen, is primary adjuvant therapy for patients with ER-positive BC, while some of them can develop acquired resistance during long-time treatment. Thus, further research on estrogen signaling is of significance to improve the prognosis of BC patients. Methods: In this study, we report that the E3 ubiquitin ligase TRIM8 acts as a novel regulator of ERα signaling. TRIM8 and ERα target genes expression levels were measured by RT-PCR, while protein expression levels were measured by western blot. CCK8 assay, clone formation, and EDU assay were used to measure cells proliferation. Wound healing assay was used to measure cells migration. Protein stability assay and protein ubiquitination analysis were used to detect ERα protein degradation. Co-immunoprecipitation assay was used to detect the interaction domain between TRIM8 and ERα. Results: TRIM8 is downregulated in BC and is associated with poor prognosis. The protein level of TRIM8 is negatively correlated with ERα. RNA-seq result revealed that estrogen signaling maybe a potential target of TRIM8. Knockdown of TRIM8 can significantly enhance BC cell proliferation and migration in vitro and in vivo. And this effect can be reversed by ERα depletion. Further mechanistic studies have shown that TRIM8 interacts with AF1 domain of ERα via its RING domain in the cytoplasm, and affects poly-ubiquitination of ERα protein. Conclusion: Our study reveals an interesting post-translational mechanism between ERα and TRIM8 in ER-positive BC, TRIM8 may be a potential therapeutic target for BC treatment.
The DDX39B/FUT3/TGFβR-I Axis Promotes Tumor Metastasis and EMT in Colorectal Cancer
Authors: He Chengcheng , Li Aimin , Lai Qiuhua , Ding Jian , Yan Qun , Liu Side , Li Qingyuan 
Published: July 2020

Abstract
Background: DDX39B is a member of the DEAD box (DDX) RNA helicase family required for nearly all cellular RNA metabolism processes. The exact role and potential molecular mechanism of DDX39B in the progression of human colorectal cancer (CRC) remain to be investigated. Methods: Western blotting and quantitative real-time PCR (qRT-PCR) were conducted to detect the expression of DDX39B in CRC tissues and cell lines. Transwell and wound healing assays were conducted to assess the migration and invasion ability of CRC cells with DDX39B overexpressed or silencing. Orthotopic transplantation model of nude mice was performed to validate CRC metastasis in vivo. RNA sequencing (RNA-seq) and RNA binding protein immunoprecipitation (RIP) assay verified the direct regulation of DDX39B on the splicing and nuclear export of FUT3 mRNA, cytoplasmic and nuclear RNA isolation confirmed the nuclear export effect of DDX39B on FUT3. qRT-PCR was conducted to quantify FUT3 splicing variants. Lectin blotting was conducted to evaluate the fucosylation level of TGFβR-I.Results: In the present study, we demonstrate that DDX39B expression was higher in CRC tissues than in adjacent normal tissues. Gain- and loss- of- function assays revealed that DDX39B facilitated the metastasis of CRC in vivo and in vitro. Mechanistically, RNA-seq and RIP showed that DDX39B upregulated FUT3 expression by binding the first exon of FUT3 mRNA, which promote the mRNA splicing and export of FUT3. RNA-seq results and qRT-PCR showed that overexpression of DDX39B may favor the longer FUT3 mRNA products that contain the complete and longer exon 2, suggesting an alternative splicing of FUT3. Upregulation of FUT3 accelerated the fucosylation of TGFβR-I, thus activating the TGFβ/SMAD signaling pathway, eventually driving the epithelial-mesenchymal transition (EMT) program and contributing to CRC progression. Conclusions: Our finding demonstrated for the first time that the DDX39B/FUT3/TGFβR-I axis promotes the progression of CRC. These findings not only provide new insight into the role of DDX39B in mRNA splicing and export and tumorigenesis, but also shed light on the effect of aberrant fucosylation on CRC progression.
Loss of Exosomal miR-146a-5p from Cancer-Associated Fibroblasts After Androgen Deprivation Therapy Contributes to Prostate Cancer Metastasis
Authors: Zhang Yu , Zhao Jing , Ding Mao , Su Yiming , Cui Di , Jiang Chenyi , Zhao Sheng , Jia Gaozhen , Wang Xiaohai , Ruan Yuan , Jing Yifeng , Xia Shujie , Han Bangmin 
Published: July 2020

Abstract
Background: Androgen deprivation therapy (ADT) is the backbone of therapy for advanced prostate cancer (PCa). Despite the good initial response, castration resistance and metastatic progression will inevitably occur. Cancer-associated fibroblasts (CAFs) may be implicated in promoting metastasis of PCa after ADT. Our aim is to investigate the role and mechanism of CAF-derived exosomes involving in metastasis of PCa after ADT. Methods: PCa cells were co-cultured with exosomes derived from 10 nM dihydrotestosterone (DHT)-treated (simulating the high androgen level of prostate cancer microenvironment） or ethanol (ETOH) -treated (simulating the castration level of prostate cancer microenvironment after ADT) CAFs, and their migration and invasion differences under castration condition were examined both in vitro and in vivo. The miRNA profiles of exosomes derived from DHT-treated CAFs and matched ETOH-treated CAFs were analysed via next generation sequencing. The transfer of exosomal miR-146a-5p from CAFs to PCa cells was identified by fluorescent microscopy. The function and direct target gene of exosomal miR-146a-5p in PCa cells were confirmed through Transwell assays, luciferase reporter, and western blot.Results: Compared with DHT-treated CAFs, exosomes derived from ETOH-treated CAFs dramatically increase migration and invasion of PCa cells under castration condition. MiR-146a-5p level in exosomes from ETOH-treated CAFs was significantly reduced. The loss of miR-146a-5p may strengthen the epithelial-mesenchymal transition (EMT) to accelerate cancer cells metastasis by modulating epidermal growth factor receptor (EGFR)/ERK pathway. Conclusions: CAFs-derived exosomal miR-146a-5p confers metastasis in PCa cells under ADT through the EGFR/ERK pathway and it may present a new treatment for PCa
Pan-Cancer Analysis Reveals that the SARS-CoV-2 Receptor ACE2 is a Protective Factor for Cancer Progression
Authors: Zhang Zhilan , Li Lin , Li Mengyuan , Wang Xiaosheng 
Published: July 2020

Abstract
Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 13 million people and has caused more than 570,000 deaths worldwide as of July 13, 2020. The SARS-CoV-2 human cell receptor ACE2 has recently received extensive attention for its role in SARS-CoV-2 infection. Many studies have also explored the association between ACE2 and cancer. However, a systemic investigation into associations between ACE2 and oncogenic pathways, tumor progression, and clinical outcomes in pan-cancer remains lacking. Methods: Using cancer genomics datasets from the Cancer Genome Atlas (TCGA) program, we performed computational analyses of associations between ACE2 expression and antitumor immunity, immunotherapy response, oncogenic pathways, tumor progression phenotypes, and clinical outcomes in 12 cancer cohorts. We also identified co-expression networks of ACE2 in cancer.Results: ACE2 upregulation was associated with increased antitumor immune signatures and PD-L1 expression, and favorable anti-PD-1/PD-L1/CTLA-4 immunotherapy response. ACE2 expression levels inversely correlated with the activity of cell cycle, mismatch repair, TGF-β, Wnt, VEGF, and Notch signaling pathways. Moreover, ACE2 expression levels had significant inverse correlations with tumor proliferation, stemness, and epithelial-mesenchymal transition (EMT). ACE2 upregulation was associated with favorable survival in pan-cancer and in multiple individual cancer types. Conclusions: ACE2 upregulation was associated with increased antitumor immunity and immunotherapy response, reduced tumor malignancy, and favorable survival in cancer, suggesting that ACE2 is a protective factor for cancer progression. Our data may provide potential clinical implications for treating cancer patients infected with SARS-CoV-2.
Interactive Effect of Hypertension and Obesity on Disability among Older People: A Observational Study
Authors: Su Peng , Yang Surong , Dong Zixi , Liang Weigen , Zhang Yunwei , Mei Jinjian , Gao Yuan , Li Qianting , Ding Hansheng , Wen Qiwu 
Published: July 2020

Abstract
Background

Both hypertension and obesity are strongly associated with disability, but these associations are in debate among older people. In this context, our study aimed to examine the interactive effect of hypertension and obesity with disability, especially including the control of blood pressure.
Methods

A cross-sectional study was conducted from August to October 2018 in Shanghai, 8648 community-dwelling individuals with a mean age of 70.39 years. Obesity was measured using the body mass index (BMI) in World Health Organization (WHO) Asia criteria. Hypertension control was defined as treatment with antihypertensive medication and a measured blood pressure of less than 140/90 mm Hg. Disability was measured using the self-reported physical self-maintenance scale (PSMS) and the instrumental activities of daily living (IADL) scale developed by Lawton and Brody. Logistic regression with 95% confidence intervals (CI) was used to explore the interactive effect of hypertension and obesity on disability.
Results

A total of 33.60% of participants reported hypertension control, 6.54% for poor hypertension control, 9.27% for ADL disability, and 32.47% for IADL disability. After adjusting social demographics and chronic conditions, versus without hypertension: in independent analyses, poor hypertension control was a risk factor (OR for ADL disability = 1.47, 95% CI = 1.10–1.96; OR for IADL disability = 1.55, 95% CI = 1.27–1.91); in interactive analyses, poor hypertension control was a risk factor in obese subset (OR for ADL disability = 1.73, 95% CI = 1.09–2.74; OR for IADL disability = 1.80, 95% CI = 1.31–2.47), but a protective factor in underweight subset (OR for ADL disability = 0.33, 95% CI = 0.18–0.62; OR for IADL disability = 0.32, 95% CI = 0.20–0.51).
Conclusions

Poor hypertension control, independent of its consequences, is a risk factor for disability among older people. In addition, hypertension and BMI status have interactive effect on disability among older people. Poor hypertension control is a risk factor among obese individuals, but a protective factor among underweight individuals.
Enlargement Of Left Ventricular Outflow Tract Using An Autologous Pericardial Patch For The Anterior Mitral Valve Leaflet And Septal Myectomy Through Trans-mitral Approach For The Treatment Of Hypertrophic Obstructive Cardiomyopathy
Authors: Zhang Hongqiang , Zhu Kai , Wang Fanshun , Sun Xiaoning , Yang Shouguo , Wang Chunsheng 
Published: July 2020

Abstract
Background: Modified Morrow procedure is the gold standard of surgical intervention for hypertrophic obstructive cardiomyopathy (HOCM). However, there are certain cases without clear exposure through the traditional trans-aortic approach; we therefore described a trans-mitral approach by enlarging left ventricular outflow tract (LVOT) using an autologous pericardial patch for the anterior mitral valve leaflet and septal myectomy. We aimed to retrospectively analyze this series of patients to reveal its safety and efficiency.Methods: We retrospectively analyzed 16 HOCM patients underwent enlargement of LVOT using an autologous pericardial patch for the anterior mitral valve leaflet and septal myectomy through trans-mitral approach in our center from January, 2016 to December, 2019. Baseline characteristics, operative details and postoperative data were extracted from our hospital medical records. Results: Of the 16 patients, there was no operative mortality. No new onset atrial fibrillation, no new onset stroke with symptoms, no permanent pacemaker implantation and no ventricular septal defects formation were observed during operation and three months follow-up. The peak pressure gradient of LVOT decreased from 97.56±23.81 mmHg to 7.56±2.13 mmHg (P < 0.01) after operation and 10.19±2.93 mmHg (P < 0.01) three months after operation. The average aortic cross-clamp time was 54.56±6.10 mins (range, 48 to 69 minutes). The systolic anterior motion (SAM) sign disappeared uneventfully in all cases. No patients had more than moderate MR.Conclusions: Enlargement of LVOT using an autologous pericardial patch for the anterior mitral valve leaflet and septal myectomy through trans-mitral approach is feasible and reliable for the treatment of certain types of HOCM cases.Trial registration: Not applicable.
Long non-coding RNA PVT1 promotes proliferation and migration of pulmonary smooth muscle cells in pulmonary arterial hypertension through miR-140-5p/Fxr1 axis
Authors: Zhao Botao , Shen Yuchao , Wu Qinghua , Yao Li , Hu Yamin 
Published: July 2020

Abstract
Background: Pulmonary arterial hypertension (PAH) is a devastating disease and long non-coding RNAs (lncRNAs) are essential for PAH progression. Also, lncRNA plasmacytoma variant translocation 1 (PVT1) plays important roles in cell proliferation and migration, however, the effect of PVT1 on pulmonary artery smooth muscle cells (HPASMCs) in PAH remains unknown. This study aimed to determine the role and underlying mechanisms of PVT1 in HPASMCs.Methods: The results demonstrated that the expression of PVT1 was upregulated in pulmonary arterial tissues and HPASMCs and was positively correlated with pulmonary arterial pressure.Results: Knockdown and overexpression of PVT1 suppressed and promoted HPASMCs proliferation and migration, respectively. Mechanical and functional studies revealed that PVT1 functioned as a competing endogenous RNA of miR-140-5p and their expressions were negatively correlated.Conclusions: Knockdown of PVT1 did not suppress proliferation and migration in HPASMCs transfected with the miR-140-5p inhibitor. Moreover, fragile X-related proteins 1 (Fxr1) was identified as the target gene of miR-140-5p. Downregulation of PVT1 decreased the level of Fxr1 while this inhibitory effect was reversed by the miR-140-5p inhibitor. In conclusion, the upregulation of PVT1 promoted proliferation and migration in HPASMCs though the miR-140-5p/Fxr1 signaling pathway, indicating PVT1 may serve as a promising diagnostic biomarker for PAH.