bluuebunny/crossref_metadata_2025_split huggingface dataset:
Profile of Congenital Heart Disease and Access to Definitive Care Among Children Seen at Gulu Regional Referral Hospital in Northern Uganda: a Four-year Experience
Authors: Aliku Twalib Olega , Beaton Andrea , Lubega Sulaiman , Dewyer Alyssa , Scheel Amy , Kamarembo Jenipher , Akech Rose , Sable Craig , Lwabi Peter 
Published: December 2020

Abstract
Objectives: The aim of this study was to describe the profile of Congenital Heart Disease [CHD] and access to definitive surgical or catheter-based care among children attending a regional referral hospital in Northern Uganda. Methods: This was a retrospective chart review of all children aged less than 17 years attending Gulu Regional Referral Hospital Cardiac clinic from November 2013 to July 2017. Results: A total of 299 children were diagnosed with CHD during the period. The median age at diagnosis was 12 months ([QR: 4 – 48] with females representing 59.2% [n=177] of cases. Neonates comprised only 7.4% [n=22]. The commonest CHD seen was ventricular septal defect [VSD] in 19.4% [n=58] of cases, followed by atrioventricular septal defect (AVSD) in 17.1% [n=51] and patent ductus arteriosus (PDA) in 15.7% [n=47]. The commonest cyanotic CHD seen was tetralogy of Fallot [TOF] in 5% [n=15], followed by double outlet right ventricle [DORV] in 4% [n=12] and truncus arteriosus in 3.4% [n=10]. Dextro-transposition of the great arteries [D-TGA] was seen in 1.3% [n=4]. At initial evaluation, 75% [n=224] of all CHD needed definitive intervention and 14% of these children [n=32] had accessed surgical or catheter-based therapy within 2 years of diagnosis. Three quarters of the cases who had intervention [n=24] had definitive care at the UHI including all 12 cases who underwent catheter-based interventions. Conclusions: There is delayed diagnosis of most rural Ugandan Children with CHD and access to definitive care is severely limited. In-country programs offer the most feasible option to increase access to definitive care.
Multi-Center Randomized Trial of Compound Kushen Injection for Decreasing Radiation- Induced Thoracic Toxicity in Lung Cancer Patients
Authors: Yu Qingxi , Wang Jun , Wang Fan , Yin Haitao , Li Xia , Yuan Shengli , Yang Fujun , Xia Bing , Jia Zhongyao , Liu Sen , Zhang Kaixian , Jiang Xuechao , Liu Fengchun , Wang Luanqiu , Deng Junji , Tong Xu , Liu Shuyan , Lin Hongsheng , Yuan Shuanghu 
Published: December 2020

Abstract
Background: Thoracic radiation therapy plays an important role in the treatment of inoperable lung cancer. However, radiotherapy-induced toxicity poses an important challenge for radiation oncologists. Research has shown that Compound Kushen Injection (CKI) has anti-inflammatory activity and can reduce toxicity when given with chemotherapy. In the present trial, we investigated whether CKI also can decrease chemoradiotherapy-induced thoracic toxicity in lung cancer patients.Methods: A prospective, open, randomized, multi-center study was performed, in which a total of 296 patients were enrolled and randomly divided 1:1 into experimental and control groups. The control group received standard chemoradiotherapy including precise thoracic radiotherapy (60 Gy/30 fractions/6 weeks) plus concurrent platinum-based chemotherapy. The experimental group received standard chemoradiotherapy plus CKI via mainline treatments of 250 ml CKI (20 ml diluted in 0.9% normal saline) daily for 20 continuous days. The incidence of adverse events and severity of thoracic toxicity after treatment were observed according to version 4.0 of the Common Terminology Criteria for Adverse Events. Adverse drug reactions (ADRs) and quality of life (QLQ-C30) also were compared between the two groups.Results: Two hundred ninety-one qualifying patients were included in the statistical analysis. Symptomatic radiation-induced thoracic toxicity was lower in the experimental group than in the control group (14.1% vs 25.6%, p=0.017). According to QLQ-C30 questionnaire findings, CKI provided superior outcomes related to pain relief, relieving fatigue, social functioning and emotional functioning (p<0.05). The rates of adverse events (26.4% vs 30.8%, p>0.05) and severe adverse events (5.4% vs 2.8%, p>0.05) did not differ significantly between the experimental and control groups.Conclusion: CKI significantly alleviated symptomatic radiation-induced thoracic toxicity, as well as pain, when given with chemoradiotherapy for lung cancer treatment.
IGF2BP3 Promotes Lung Cancer Progression Through FTO Dependent m6A Modification by Stabilizing N-myc
Authors: Wang Xiaolin , Chen Yong , Min Lingfeng , Shi Hongcan , Lu Shichun , Sun Chao , Jin Weiguo , Shu Yusheng 
Published: December 2020

Abstract
Background: N6-methyladenosine modification has been involved in various biological processes. However, its role in non-small cell lung cancer has not been well studied. Here, we show that IGF2BP3, as an transcription factor, plays a critical oncogenic role in non-small-cell lung cancer carcinogenesis through activating FTO expression and inducing aberrant m6A modification. Methods: To evaluate the role of IGF2BP3 in non-small-cell lung cancer, we performed cell proliferation and cell cycle assays in three lung cancer cell lines. Lung cancer mouse model is used to examine the effects of IGF2BP3/FTO/N-myc on lung proliferation potentials in vivo. We analyzed the correlation between IGF2BP3 and FTO, IGF2BP3 and N-myc protein in colon cancer patients by Pearson correlation. To finally explore the relationship of IGF2BP3/FTO/N-myc, we used western blots, proliferation and cell cycle assays to confirm that IGF2BP3 may regulate lung cancer progression through FTO dependent m6A modification by stabilizing N-myc.Results: We first identified that IGF2BP3 overexpressed in non-small-cell lung cancer tissue and cells. Then, we showed that FTO was the dysregulated factor responsible for the abnormal N6-methyladenosine modification in non-small-cell lung cancer. The loss-of-function assay demonstrated that IGF2BP3 enhances FTO-mediated cell proliferation and promotes cell apoptosis, through regulating expression of target gene N-myc by reducing m6A level in mRNA transcript. Conclusion: Our study demonstrates the functional importance of IGF2BP3 and N6-methyladenosine methylation modification in the tumor progression of non-small-cell lung cancer, and provides profound insights into lung carcinogenesis and drug response.
HPV16 E7 Oncoprotein As a Predictor of Diagnosis and Prognosis in Patients with Cervical Lesions
Authors: Shuai Guangnan , Xu Junhui , Liu Meihua , Zhu Xueping , Zhang Na , Qu Pengpeng 
Published: December 2020

Abstract
Backgroud：The early diagnosis and treatment of HSIL is a key measure to prevent the occurrence of cervical cancer. Although the methods of cervical cancer screening are becoming more and more abundant, some patients still have unnecessary colposcopy referrals. This study aim to explore the value of human papillomavirus 16 (HPV16) E7 oncoproteinin cervical lesion screening and risk assessment of the prognosis for more effective colposcopy. Method: HPV16 E7 oncoprotein in cervical exfoliated cells was detected by using E7 Oncoprotein (HPV16) Diagnostic Kit (Magnetic Partical Chemiluminescence Method). In the first part, HPV16 E7 oncoprotein in different degrees of cervical lesions was retrospectively compared to find the best critical value; In the second part, the value of this test was verified ; In the third part, the women diagnosed as low-grade squamous intraepithelial lesions (LSIL) or normal were followed up for 3 years and the outcomes were compared. Results: In the first part, the expression of HPV16 E7 oncoprotein was positively correlated with the degree of cervical lesion; The critical value determined by ROC curve is 8.68ng/ml, which is accurate in the diagnosis of high-grade squamous intraepithelial lesions (HSIL) and invasive carcinoma of cervix (CA); In the second part, there were higher sensitivity(87.1) and specificity(70) for E7 oncoprotein; HPV16 E7 oncoprotein has higher consistency with pathological examination in detection of HSIL or cervical cancer（0.573 vs 0.369) than TCT; In the third part，HPV16 E7 oncoprotein has a high positive predictive value (82.4%) and positive likelihood ratio (4.43) for the prognosis of patients with LSIL and below. Conclusions: The status of HPV16E7 oncoprotein shows important clinical value for the detection and prediction of cervical lesions. Patients with positive HPV16 E7 oncoprotein are more likely to develop the disease and have a higher risk of disease progression.
Neuropilin 1 and Neuropilin 2 Gene Invalidation or Pharmacological Inhibition Reveals Their Relevance for the Treatment of Metastatic Renal Cell Carcinoma
Authors: Dumond Aurore , Brachet Etienne , Durivault Jérôme , Vial Valérie , Puszko Anna , Lepelletier Yves , Montemagno Christopher , Pagnuzzi-Boncompagni Marina , Hermine Olivier , Garbay Christiane , Lagarde Nathalie , Montes Matthieu , Demange Luc , Grépin Renaud , Pagès Gilles 
Published: December 2020

Abstract
BackgroundDespite the improvement of relapse-free survival mediated by anti-angiogenic drugs like sunitinib (Sutent ®), or by combinations of anti-angiogenic drugs with immunotherapy, metastatic clear cell Renal Cell Carcinoma (mccRCC) remain incurable. Hence, new relevant treatments are urgently needed. The VEGFs coreceptors, Neuropilins 1, 2 (NRP1, 2) are expressed on several tumor cells including ccRCC. We analyzed the role of the VEGFs/NRPs signaling in ccRCC aggressiveness and evaluated the relevance to target this pathway.MethodsWe correlated the NRP1, 2 levels to patients’ survival using online available data base. Human and mouse ccRCC cells were knocked-out for the NRP1 and NRP2 genes by a CRISPR/Cas9 method. The number of metabolically active cells was evaluated by XTT assays. Migration ability was determined by wound closure experiments and invasion ability by using Boyden chamber coated with collagen. Production of VEGFA and VEGFC was evaluated by ELISA. Experimental ccRCC were generated in immuno-competent/deficient mice. The effects of a competitive inhibitor of NRP1, 2, NRPa-308, was tested in vitro and in vivo with the above-mentioned tests and on experimental ccRCC. NRPa-308 docking was performed on both NRPs.ResultsKnock-out of the NRP1 and NRP2 genes inhibited cell metabolism and migration and stimulated the expression of VEGFA or VEGFC, respectively. NRPa-308 presented a higher affinity for NRP2 than for NRP1. It decreased cell metabolism and migration/invasion more efficiently than sunitinib and the commercially available NRP inhibitor EG00229. NRPa-308 presented a robust inhibition of experimental ccRCC growth in immunocompetent and immunodeficient mice. Such inhibition was associated with decreased expression of several pro-tumoral factors. Analysis of the TCGA database showed that the NRP2 pathway, more than the NRP1 pathway correlates with tumor aggressiveness only in metastatic patients.ConclusionsOur study strongly suggests that inhibiting NRPs is a relevant treatment for mccRCC patients in therapeutic impasses and NRPa-308 represents a relevant hit.
Berberine Suppresses Bladder Cancer Cell Proliferation by Inhibiting JAK1-STAT3 Signaling via Upregulation of miR-17-5p
Authors: Xia Yangyang , Chen Shouzhen , Cui Jianfeng , Wang Yong , Liu Xiaochen , Shen Yangli , Gong Li , Jiang Xuewen , Wang Wenfu , Zhu Yaofeng , Sun Shuna , Li Jiaxiang , Zou Yongxin , Shi Benkang 
Published: December 2020

Abstract
Background: Berberine (BBR), an active component extracted from Coptis chinensis, has shown anti-tumor effects in multiple tumors. However, the underlying mechanisms haven’t been fully elucidated. In this study, the effects of BBR on bladder cancer (BCa) cells and the underlying mechanisms were investigated both in vivo and vitro. Methods: MTT, colony formation, EdU incorporation assays and xenograft tumor models were performed to evaluate the anti-proliferation effects of BBR on BCa cells in vivo and vitro. The roles of BRR in migration and invasion of BCa cells were investigated by wound-healing, transwell migration and invasion assays. The apoptosis and senescence induced by BBR were determined by flow cytometry, tunel assay and senescence-associated β-galactosidase (SA-β-gal) activity assay. Potential candidate targets were screened using western blot. The relationships between miR-17-5p and JAK1-STAT3 pathway were then predicted using in-silico analysis and identified by dual-luciferase reporter assay. The regulatory mechanism of miR-17-5p mediated suppression of JAK1-STAT3 pathway caused by BBR treatment was validated by qRT-PCR and western blot.Results: We found that BBR showed significant cytotoxic effects against bladder cancer (BCa) cell lines both in vivo and vitro, with much lower cytotoxic effects on human normal urothelial cell line SV-HUC-1. BBR treatment induced DNA replication defects and cycle cell arrest, resulting in apoptosis or cell senescence, depending on p53 status, in BCa cells. Mechanically, BBR exerted anti-tumor effects on BCa cells through inhibiting JAK1-STAT3 signaling via promoting expression of miR-17-5p, which directly bound to 3’ UTR of JAK1 and STAT3 and downregulated their expressions. Conclusion: Our results demonstrate that BBR exerts anti-tumor effects through perturbing JAK1-STAT3 signaling via upregulating expression of miR-17-5p in BCa cells, and BBR may serve as a potential therapeutic option for BCa treatment.
WITHDRAWN: GCC2 is a New Biomarker for Diagnosis of Early Non-Small Cell Lung Cancer and A Potential Target to Reverse Epithelial to Mesenchymal Transition
Authors: Jeong Hyesun , Choi Byeong Hyeon , Jung Jik-han , Shin Hyunku , Park JinA , Kang Ka-Won , Quan Yu Hua , Yu Jewon , Park Ji-Ho , Park Yong , Choi Yeonho , Kim Hyun Koo , Hong Sunghoi 
Published: December 2020

Abstract
Background: Nano-sized exosomes (30–150 nm) are cell membrane-encapsulated vesicles that contain nucleic acids and proteins. Specific markers detecting non-small cell lung cancer (NSCLC) cell-derived exosomes in the blood circulation remain unidentified. Here, we report a new biomarker distinguishing cancer from non-cancer exosomes that also involved in epithelial to mesenchymal transition for cancer treatment.Methods: Exosomes were isolated from plasma of patients with various pathological stages of NSCLC and NSCLC cell lines, human pulmonary alveolar epithelial cells by size exclusion chromatography and characterized by Nanoparticle Tracking Analysis and western-blotting. The exosomes were lysed and applied to proteomic analysis. The expression levels of the GCC2 proteins from NSCLC patients were analyzed by ELISA assays, and the effects by GCC2 shRNA were analyzed by real-time RT-PCR, cell migration and colony formation assays.Results: A protein GRIP and coiled-coil domain-containing 2 (GCC2), which is involved in endosome-to-Golgi transport, was identified by the proteomics analysis of exosomes isolated from NSCLC cell lines. The GCC2 protein expression levels were increased in the exosomes derived from patients with early-stage NSCLC compared with healthy controls. The receiver operating characteristic curve of exosomal GCC2 revealed 94.74% sensitivity and 75.00% specificity, and AUC of 0.875. GCC2 knockdown experiments by GCC2 shRNA showed reduced exosome secretion in cancer cell lines, which altered the molecular and cellular properties, such as the expression levels of mesenchymal-to-epithelial genes, and cellular growth and motility.Conclusion: GCC2 represents a promising biomarker for early diagnosis of NSCLC and a therapeutic target for future cancer treatment.
The Significance of Prognostic m6A RNA Methylation Regulators in Tumor Immune Environment and Immune Therapy of Hepatocellular Carcinoma
Authors: Xu Qianhui , Xu Hao , Deng Rongshan , Li Nanjun , Mu Ruiqi , Qi Zhixuan , Shen Yunuo , Wang Zijie , Wen Jingchao , Zhao Jiaxin , Weng Di , Huang Wen 
Published: December 2020

Abstract
Background: Hepatocellular carcinoma (HCC) ranks the sixth prevalent tumors with high mortality in the world. N6-methyladenosine (m6A) might act an important regulatory factor in tumorigenesis and progression. Here, we aimed to elucidate the potential player of m6A RNA methylation regulators in tumor immune microenvironment (TIME) and immune checkpoint blockade (ICB) therapy of HCC.Methods: Transcriptome data as well as corresponding patient clinical data obtained from publicly TCGA-LIHC databank were integrative analyzed. To reveal the landscape of TIME in HCC, ESTIMATE algorithm, ssGSEA method and CIBERSORT analysis were conducted. And the correlations of m6A regulators with ICB-related genes was analyzed. Taking advantage of consensus clustering, two different HCC categories were screened. We analyzed the correlation of clustering result with TIME and ICB treatment. Then we yielded a robust signature of six m6A regulators by employing univariate proportional hazards and LASSO analysis. Survival analysis (Kaplan-Meier method), ROC curve analysis and Cox regression analysis were further performed. Then, these results were validated in ICGC-LIRI cohort. Subsequently, the relationship of prognostic risk signature with immune infiltration and ICB therapy were analyzed. Finally, the impact of ZC3H13 upon TIME and ICB immunotherapy was uncovered. Results: We identified that 19 out of 21 m6A key regulators significantly overexpressed in tumor tissue relative to paired normal sample. The m6A regulators-based case clusters were significantly correlated with overall survival (OS), immune score, immunological signature, tumor infiltrating immune cells, and ICB-associated genes expression level. Six m6A-related genes signature (YTHDF1, YTHDF2, IGF2BP3, KIAA1429, METTL3, and ZC3H13) were generated, which possess robust and stable prognostic validity and could serve as an independent prognosis predictive factor. Besides, risk score significantly correlated with immune score, immune-related signature, infiltrating immune cells (i.e., B cells, etc.,) and ICB molecules (i.e., CTLA4, etc.,). Finally, we corroborated ZC3H13 had intimate relationship with TIME and ICB therapy in HCC. Conclusion: Collectively, we herein identified two distinct HCC subgroups and established m6A regulators-based signature as a robust prognostic indicator and elucidated the crucial role of m6A regulators (ZC3H13) in immune cell infiltration and immunotherapy, which might contribute to clinical management and prognosis prediction of HCC.
Bioreduction of Cr(VI) by Viable Cells and Cell-Free Extract of a Moderate Halophile, Halomonas Smyrnensis KS802 and Evaluation of Their in Vitro Efficacy in Tannery Effluent
Authors: Biswas Jhuma , Paul AK 
Published: December 2020

Abstract
The present study was aimed to characterize the chromate reducing ability of cells and cell-free extract (CFE) of Halomonas smyrnensis KS802 (GenBank Accession No. KU982965) and evaluate their effectiveness in tannery effluents. Viable cells of the strain reduced 200 µM Cr(VI) in basal medium for halophiles (MH) in 10 h and was inversely proportional to Cr(VI) concentrations. The rapid reduction by cells (10⁹ cells/mL) was achieved with 7.5% NaCl, at pH 7 and 37°C which increased with increasing cell density (10¹° cells/mL). While acetate, Cu³⁺, Fe³⁺, SO₄²⁻, and CO₃²⁻ were stimulating the reduction, the inhibitors retarded the process significantly. The NADH-dependent chromate reduction of the CFE was found to be constitutive with Km and Vmax values of 56.58 µM and 3.37 µM/min/mg protein respectively. The optimal reductase activity of the CFE was evident at 200 µM Cr(VI), 10% NaCl, pH 8.0 and at 45°C. A higher concentration of CFE and electron donors increased the enzyme activity but was impacted negatively by toxic metals and anions. Both the cells and CFE were capable of reducing Cr(VI) remarkably from tannery effluent. FTIR and XRD spectra of chromate reducing cells confirmed possible complexation of reduced Cr-species with functional groups on cell surface.
An Access Control Model for the Internet of Things Based on Zero-Knowledge Token and Blockchain
Authors: Song Lihua , Ju Xinran , Zhu Zongke , Li Mengchen 
Published: December 2020

Abstract
Information security has become the focus problem in the Internet of Things, and the traditional centralized access control model is faced with threats such as single point failure, internal attack, and central leak. In this paper, we proposed a model to improve the access control security of the Internet of Things, which is based on zero-knowledge proof and smart contract technology in the blockchain. Firstly, we deployed the attribute information of access control in the blockchain, which relieves the pressure and credibility problem brought by the third-party information concentration; Secondly, the encrypted access control token is used to gain the access permission of the resources, which makes the user's identity invisible and effectively avoids the attribute ownership exposure problem; Besides, the use of smart contracts solves the problem of low computing efficiency of Internet of Things devices and the waste of blockchain computing power resources; Finally, a prototype of Internet of Things access control system based on blockchain and zero-knowledge proof technology is implemented. The test analysis results show that the model achieves effective attribute privacy protection, compared with the Attribute-Based Access Control model of the same security level, the access efficiency increases linearly with the increase of access scale.
Long Bone Fracture Reduction and Deformity Correction Using the Hexapod External Fixator With a New Method: a Feasible Study and Preliminary Results
Authors: Liu Yanshi , Li Hong , Liu Jialin , Zhang Xingpeng , Yushan Maimaiaili , Liu Zhenhui , Ma Chuang , Yusufu Aihemaitijiang 
Published: December 2020

Abstract
Background: The hexapod external fixator (HEF), such as the Taylor spatial frame (TSF), offering the ability of simultaneous correction of the multidirectional deformities without frame modification, whereas there are so many parameters for surgeons to measure and subjective errors will occur inevitably. The purpose of this study was to evaluate the effectiveness of a new method based on computer-assisted three-dimensional (3D) reconstruction and hexapod external fixator for long bone fracture reduction and deformity correction without calculating the parameters needed by the computer program.Methods: This retrospective study consists of 25 patients with high-energy tibial diaphyseal fractures treated by the HEF at our institution from January 2016 to June 2018, including 22 males and 3 females with a mean age of 42 years (range 14-63 years). Hexapod external fixator treatments were performed due to primary and definitive management of multiplanar posttraumatic deformity and/or severe soft-tissue damage that were not suitable for internal fixation in the tibia. Computer-assisted 3D reconstruction and trajectory planning of the reduction by Mimics were applied to perform virtual fracture reduction and deformity correction. The electronic prescription derived from the length changes of the six struts were calculated by SolidWorks. Fracture reduction was conducted by adjusting the lengths of the six struts according to the electronic prescription. The standard anteroposterior (AP) and lateral X-rays after reduction were taken to evaluate the effectiveness.Results: All patients acquired excellent functional reduction (most cases achieved anatomical reduction) in our study. The mean coronal plane translation (1.0±1.1 mm), coronal plane angulation (0.8±1.2°), sagittal plane translation (0.8±1.0 mm) and sagittal plane angulation (0.3±0.8°) after correction were all less than those (6.1±4.9 mm, 5.2±3.2°, 4.2±3.5 mm, 4.0±2.5°) before correction (P<0.05).Conclusion: The computer-assisted three-dimensional reconstruction and hexapod external fixator-based method allows surgeons to conduct long bone fracture reduction and deformity correction without calculating the parameters needed by the computer program. Considering the radiologic exposure, this method is suggested to apply in those unusually complex cases with extensive soft tissue damage and internal fixation is impossible or inadvisable.