bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and Validation of a Unique Gignature of Cancer Stemness-related Genes for Predicting the Overall survival of Colorectal Cancer Patients
Authors: Wei Ran , Quan Jichuan , Li Shuofeng , Lu Zhao , Guan Xu , Jiang Zheng , Wang Xishan 
Published: December 2020

Abstract
Background: Cancer stem cells (CSCs), which are characterized by self-renewal and plasticity, are highly correlated with tumor metastasis and drug resistance. To fully understand the role of CSCs in colorectal cancer (CRC), we evaluated the stemness traits and prognostic value of stemness-related genes in CRC.Methods: In this study, the data from 616 CRC patients from The Cancer Genome Atlas (TCGA) were assessed and subtyped based on the mRNA expression-based stemness index (mRNAsi). The correlations of cancer stemness with the immune microenvironment, tumor mutational burden (TMB) and N6-methyladenosine (m6A) RNA methylation regulators were analyzed. Weighted gene co-expression network analysis (WGCNA) was performed to identify the crucial stemness-related genes and modules. Furthermore, a prognostic expression signature was constructed using Lasso-penalized Cox regression analysis. The signature was validated via multiplex immunofluorescence staining of tissue samples in an independent cohort of 48 CRC patients.Results: This study suggests that high mRNAsi scores are associated with poor overall survival in stage Ⅳ CRC patients. Moreover, the levels of TMB and m6A RNA methylation regulators were positively correlated with mRNAsi scores, and low mRNAsi scores were characterized by increased immune activity in CRC. The analysis identified 2 key modules and 34 key genes as prognosis-related candidate biomarkers. Finally, a 3-gene prognostic signature (PARPBP, KNSTRN and KIF2C) was explored together with specific clinical features to construct a nomogram, which was successfully validated in an external cohort. Conclusions: There is a unique correlation between CSCs and the prognosis of CRC patients, and the novel biomarkers related to cell stemness could accurately predict the clinical outcomes of these patients.
Therapeutic Potential of CUDC-907 (Fimepinostat) for Hepatocarcinoma Treatment Revealed by Tumor Spheroids-based Drug Screening
Authors: Liao Wei , Yang Wanren , Zhang Yue , Zeng Fanhong , Xu Jiecheng , Yan Zhengming , Pan Mingxin , Xu Xiaoping , Zhou Shuqin , Zeng Min , Weng Jun , Han Xu , Li Shao , Li Yang , Liang Kangyan , Peng Qing , Gao Yi 
Published: December 2020

Abstract
Background: Cancer is the second leading cause of death globally. However, most of the new anti-cancer agents screened by traditional drug screening methods fail in the clinic because of lack of efficacy. One of the reasons for this dilemma is that the two-dimensional (2D) culture cancer cell lines could not represent the in vivo cancer cells well. Fortunately, the development of a three-dimensional (3D) culture technique helps in this problem. Methods: The high-throughput spheroid culture plate was fabricated by using 3D print technique and agarose. 4 hepatocarcinoma (HCC) cell lines were 3D cultured to screen 19 small molecular agents based on the spheroid culture plate. 3D cultured primary HCC cells and tumor-bearing mice model were established to verify the candidate anti-hepatocarcinoma agent. Cell function experiments and western blotting were conducted to explore the anti-hepatocarcinoma mechanism of the candidate agent. Results: Based on the previous study, we established an in vitro 3D drug screening method by using our invented spheroid culture device and found that CUDC-907 can serve as a potent anti-hepatocarcinoma agent. The study data show that CUDC-907 (fimepinostat), a novel dual acting inhibitor of phosphoinositide 3-kinase (PI3K) and histone deacetylase (HDAC), has potent inhibitory effects on HCC cell lines and primary HCC cells in vitro, Animal studies have shown that CUDC-907 can also suppress HCC cells in vivo. Furthermore, we investigated the antitumor mechanism of CUDC-907 in HCC cells. We found that it inhibits the PI3K/AKT/mTOR pathway and downregulates the expression of c-Myc, leading to the suppression of HCC cells. Conclusion: Our results suggest that CUDC-907 can be a candidate anti-HCC drug, and the 3D in vitro drug screening method based on our novel spheroid culture device is promising for drug screening.
Bi-specific Antibody Y111, Targeting PD-L1 and CD3 Considerably Enhances the Therapeutic Efficacy of Adoptive Transferred Vγ2Vδ2 T Cells
Authors: Yang Rui , Shen Susu , Gong Cheng , Wang Xin , Luo Fang , Luo Fengyan , Lei Yang , Wang Zili , Xu Shasha , Ni Qian , Xue Yan , Fu Zhen , Zeng Liang , Fang Lijuan , Yan Yongxiang , Zhang Jing , Gan Lu , Yi Jizu , Zhou Pengfei 
Published: December 2020

Abstract
Background: Anti-cancer immunotherapy based on the adoptive transfer of Vγ2Vδ2 T cells has benefited to some patients in clinical trials, but the overall responses are inconsistent. Therefore, new strategies are urgently needed to improve the current therapy.Methods: In this study, a designed bispecific antibody Y111, which binds to both CD3 and PD-L1, is applied to optimally potentiate Vγ2Vδ2 T cell-based killing of cancer cells. The binding activities of Y111 was determined by Flow cytometry. CFSE/PI-based flow cytometry was applied to check the re-directed killing ability induced by Y111 in the condition of using T cell subsets, or expanded- and purified- Vγ2Vδ2 T cells as effector cells. Moreover, expanded- and purified- Vγ2Vδ2 T cells were co-cultured with tumor cells in the presence/absence of Y111 to assess the activation, degranulation, and cytokine production by intracellular cytokine staining, and CBA method. Finally, NPG-based subcutaneous tumor mouse models were used to check the in vivo therapeutic efficacy of the combination of transfused Vγ2Vδ2 T cells and Y111.Results: Due to its binding activities, Y111 apparently prompts fresh αβ-mediated lysis of tumor cell line H358 cells, but spare the effect on the fresh enriched Vγ2Vδ2 T cells from the same donors. However, Y111 increases cytotoxicity of expanded and purified Vγ2Vδ2 T cells against various NSCLC-derived tumor cell lines in a tumor cell dependent fashion. Y111 also prompted the releases of granzyme B, IFNγ and TNFα. Supporting to these observations in vitro, a combination of adoptive transferring Vγ2Vδ2 T cell and Y111 into the tumor-bearing NPG mice inhibited the growth of the established tumors in the mice.Conclusions: Taken together, our data suggest clinical potential for adoptive transferring the bispecific antibody-armored Vγ2Vδ2 T cells to treat solid tumors, such as NSCLC.
LncRNA APOC1P1-3 Promoting Anoikis-resistance of Breast Cancer Cells
Authors: Lu Qi , Wang Li , Zhu Ping , Gao Yabiao , Li Luying , Wang Xue , Jin Youping , Zhi Xiuling , Yu Jerry , Li Xin , Qin Xingjun , Zhou Ping 
Published: December 2020

Abstract
Background: Anoikis resistance plays a critical role in the tumor metastasis by allowing survival of cancer cells in the systemic circulation. We previously showed that long non-coding RNAs APOC1P1-3 (lncRNA APOC1P1-3) inhibits breast cancer cell apoptosis. However, its role in the anoikis resistance remains unclear. Methods: We induced anoikis resistance in two breast cancer cell lines (MCF-7 and MDA-MB-231) under anchorage-independent culture condition and studied the effects of lncRNA APOC1P1-3 on the apoptosis. The Dual-Luciferase activity assay were used to whether miRNA-188-3P can specifically bind to lncRNA APOC1P1-3. We further explored the role of APOC1P1-3 in the lung metastasis by injecting MDA-MB-231 and MDA-MB-231-APOC1P1-3-knock-down cells in the female BALB/c nude mice.Results: We found that it suppressed early apoptosis of these cells by gain or loss of their function, respectively. We further explored its mechanism related to anoikis resistance, and found this molecule promoted the resistance via activating Caspase 3, 8, 9 and PARP. Moreover, it was specifically binding to the target miRNA-188-3p to block its inhibition of Bcl-2 (an anti-apoptosis protein). These findings suggest that lncRNA APOC1P1-3 plays an important role in the development of breast cancer metastasis via anoikis resistance. Conclusions: This study demonstrates that lncRNA APOC1P1-3 can promote the anoikis resistance of breast cancer cells and specifically bind to miRNA-188-3p acting as a “sponge” to block the inhibition of anti-apoptotic protein Bcl-2.
Generation of heritable double muscle buttocks rabbits via myostatin mutation with CRISPR/Cas9 system
Authors: Zhang Yu , Zheng Yalin , Wu Liyan , Li Zhipeng , Xiao Ning , Li Hongli , An Lei , Shi Deshun , Liu Qingyou , Cui Kuiqing 
Published: December 2020

Abstract
Background

Myostatin (MSTN) is a member of the transforming growth factor (TGF-β) superfamily and is considered to be a negative regulator that inhibits muscle development and regeneration, inactivity of MSTN gene may affect the development and regeneration of muscle in a few of animals.
Results

In the present study, the muscle mass negative regulator gene myostatin (MSTN) was knocked out at two novel sits in exon3, and the function of these mutation was determined in the offspring rabbits. The typical double muscle phenotype with hyperplasia and hypertrophy of muscle fiber was observed in the MSTN KO rabbits, and similar phenotype was confirmed in the F1 generation rabbits. The body weight of MSTN-KO+/− rabbits 3708 ± 43.06 g were significant heavier at 180 days than that of control WT rabbit 3224 ± 48.64 g (P < 0.001). Fourteen litters of F1 generation rabbits were produced, and the mutation of MSTN could be stably inherited in the MSTN KO rabbits.
Conclusions

Heritable double muscle buttocks rabbits via myostatin mutation with CRISPR/Cas9 system were generated, which will be valuable in meat rabbits breeding and a useful animal model for the study of human muscle development related diseases.
Improving Biomedical Named Entity Recognition with Label Re-correction and Knowledge Distillation
Authors: Zhou Huiwei , Liu Zhe , Lang Chengkun , Lin Yingyu , Hou Junjie 
Published: December 2020

Abstract
Background: Biomedical named entities recognition is one of the most essential tasks in biomedical information extraction. Previous studies suffer from inadequate annotation datasets, especially the limited knowledge contained in them. Methods: To remedy the above issue, we propose a novel Chemical and Disease Named Entity Recognition (CDNER) framework with label re-correction and knowledge distillation strategies, which could not only create large and high-quality datasets but also obtain a high-performance entity recognition model. Our framework is inspired by two points: 1) named entity recognition should be considered from the perspective of both coverage and accuracy; 2) trustable annotations should be yielded by iterative correction. Firstly, for coverage, we annotate chemical and disease entities in a large unlabeled dataset by PubTator to generate a weakly labeled dataset. For accuracy, we then filter it by utilizing multiple knowledge bases to generate another dataset. Next, the two datasets are revised by a label re-correction strategy to construct two high-quality datasets, which are used to train two CDNER models, respectively. Finally, we compress the knowledge in the two models into a single model with knowledge distillation. Results: Experiments on the BioCreative V chemical-disease relation corpus show that knowledge from large datasets significantly improves CDNER performance, leading to new state-of-the-art results.Conclusions: We propose a framework with label re-correction and knowledge distillation strategies. Comparison results show that the two perspectives of knowledge in the two re-corrected datasets respectively are complementary and both effective for biomedical named entity recognition.
Evaluation of a Clinical Decision Support System for Rare Diseases - A Qualitative Study
Authors: Schaaf Jannik , Sedlmayr Martin , Sedlmayr Brita , Prokosch Hans-Ulrich , Storf Holger 
Published: December 2020

Abstract
BackgroundRare Diseases (RDs) are difficult to diagnose. Clinical Decision Support Systems (CDSS) could support the diagnosis for RDs. The MIRACUM (Medical Informatics in Research and Medicine) consortium developed a CDSS for RDs based on distributed clinical data from ten German university hospitals. To support the diagnosis for difficult patient cases, the CDSS uses data from the different hospitals to perform a patient similarity analysis in order to obtain an indication of a diagnosis. To optimize our CDSS, we conducted this qualitative study to investigate the usability of the CDSS with its functionality and information included. Methods A Thinking Aloud Test (TA-Test) was performed with RDs experts recruited from Rare Diseases Centres (RDCs) at the MIRACUM locations which were specialized in the diagnosis and treatment of RDs.An instruction sheet with tasks was prepared that the participants should perform with the CDSS during the study. Participants were asked to share any thoughts about the CDSS. The TA-Test was recorded on audio and video. A questionnaire was handed out at the end of the study including the System Usability Scale (SUS). Afterwards, the data was analysed with the qualitative content analysis according to Mayring, which includes a category-guided deductive approach.ResultsA total of eight experts were included in the study since eight MIRACUM locations have established an RDC.The results show that more detailed information about the patients, such as descriptive attributes or findings, are needed. The given functionality of the CDSS was rated positively, such as the function for the overview of similar patients and medical history. However, there is a lack of transparency regarding the results of the CDSS patient similarity analysis. The participants stated that the system should present exactly which symptoms, diagnosis etc. have matched. Regarding usability, the CDSS received a score of 73.21 points according to the SUS, which is ranked as a good usability.ConclusionsThis qualitative study investigated the usability of a CDSS of RDs. Despite the promising results, the CDSS still needs some revisions before use in clinical practice, e.g. by improving the transparency of the patient similarity analysis.
Role of Sequential Functional Echocardiography in Predicting Clinically Apparent Patent Ductus Arteriosus in Preterm Very Low Birth Weight Newborns-An Observational Study
Authors: Bhardwaj Anchala , SAILI ARVIND , Yadav Dinesh Kumar , Kumar Ajay 
Published: December 2020

Abstract
Background The management of patent ductus arteriosus in preterm neonates continues to be a topic of discussion and controversy. Prolonged ductal patency in preterm neonates has been associated with significant short and long term morbidities and with increased mortality however, policy of routine treatment of all during neonatal period has failed to show significant improvement in long term outcome. Echocardiography has emerged as a promising modality to screen the newborns at risk of adverse effects of ductal shunting. This helps in identifying PDAs that require treatment to ultimately prevent unnecessary therapy or delay of necessary therapy. There are multitude of studies that have evaluated large number of echocardiographic markers for their predictive utility but only few have included all ductal markers together in a single study. The reported sensitivity (26-100%) and specificity (6-100%) of echocardiographic markers vary over a wide range. Thus, this study was planned with an aim to assess the predictive utility of all available ductal markers and their added advantage of having all over few ones in clinically apparent PDA in preterm VLBW newborns.Methods It was an observational prospective study conducted in tertiary care NICU at Lady Hardinge Medical College, Delhi. Fifty preterm very low birth weight (VLBW) newborns underwent four sequential Echo scans within first 72 hrs; first scan within 12 hours then at 24 hrs ,48 hrs and 72 hrs of age and were monitored clinically for the signs of PDA up to two weeks of life or discharge whichever comes later.Results The Ductal diameter, pulsatile ductal flow pattern, Left pulmonary artery (LPA) velocity, Left atrial to aortic width (La/Ao) ratio, Left atrial volume index (LAVI), Left ventricle to aortic width (Lv/Ao) ratio, E/A ratio and Left ventricular output/superior vena caval (LVO/SVC) flow ratio predicted clinically apparent PDA during first 72 hours of life.Conclusion This study provides insights into the predictive utility of other ductal echo markers along with the routinely measured conventional ones during first 72 hours of life in preterm VLBW newborns.
A modified intrafocal pinning technique with three-dimensional planning to facilitate volar plating in dorsally comminuted AO/OTA C2 and C3 distal radius fractures
Authors: Gui Xue-yang , Shi Hong-fei , Xiong Jin , Chen Yi-xin , Wang Jun-fei , Huang Jie , Qiu Xu-sheng , Wang Yin-he 
Published: December 2020

Abstract
Backgrounds: The aim of this study was to assess the efficacy of a modified intrafocal pinning technique with three-dimensional (3D) planning to facilitate volar plating in dorsally comminuted intra-articular distal radius fractures.Methods: In total 35 AO/OTA type C2 and C3 fractures were finally included. The 3D digital model of the fracture was reconstructed based on preoperative computed tomographic (CT) images, with the displacement of the comminuted dorsal fragment and the intra-articular fragment analyzed for preoperative planning. During operation, a modified intrafocal pinning technique was applied percutaneously from the dorsal aspect of the radius to reduce the collapsed intra-articular fragment following volar plating. Adequate reduction was confirmed in all of patients considering radial height, radial inclination and volar tilt in postoperative radiographs.Results: No significant fracture re-displacement was observed in most of the cases during a mean follow-up period of 17.4 months, except for two patients with the C3 fracture. All of the patients achieved adequate clinical ROMs at 12 months postoperatively, with a mean DASH score of 12.0. Most of the patients achieved an excellent (n = 21) or good (n = 12) Gartland and Werley wrist score.Conclusions: Our modified intrafocal pinning technique with 3D planning contributes to a satisfactory clinical and radiological outcome in dorsally comminuted intra-articular distal radius fractures fixed with a volar locking plate.Trial registration: Not applicable because the design of the study is retrospective.
An Improved AODV&nbsp;Routing Security Algorithm Based on Blockchain in Ad Hoc&nbsp;Network
Authors: Ran Conglin , Yan Shuailing , Huang Liang , Zhang Lei 
Published: December 2020

Abstract
Ad Hoc network is a special network with no center and dynamic topology changes. Due to the free mobility of nodes, routing security has always been a bottleneck problem that plagues network development. Therefore, this paper proposes a multi-path QoS (Quality of Service) routing security algorithm based on blockchain by improving the traditional AODV (Ad hoc On-Demand Distance Vector) protocol (AODV-MQS). The algorithm first establishes a blockchain network and saves the state of all nodes by making the intermediate nodes on the chain. Then the smart contract in the blockchain is set to filter out the nodes that meet the QoS constraints. Finally, two largest unrelated communication paths are found in the blockchain network through smart contract, one of which is the main path and the other is the standby path. Simulation experiments show that this algorithm has better performance than other algorithms in an unsafe environment.
Quality Blues: Indigenous Knowledge of Natural Indigo Identification in Southern China
Authors: Shi Yuru , Zhang Libin , Wang Lu , Li Shan , Qiu Zuchuan , Ding Xiaoyong , Wang Yuhua 
Published: December 2020

Abstract
Background: As one of the oldest traditional dyes, natural indigo is commonly used for centuries by the people worldwide. In the process of indigo production, indigenous people have formed unique knowledge of indigo identification because the indigo identification is crucial for indigo quality control and the dyeing effects. However, such indigenous knowledge is rarely documented and explained. Therefore, the aims of this study were to i) document and assess the indigenous knowledge of local people identifying the natural indigo paste and ii) to explore the characteristics and material basis of such indigenous knowledge.Method: Three ethnobotanical studies were conducted in 2019 and 2020. A total of 283 traditional indigo-paste artisans were interviewed in Guizhou, Yunnan, and Fujian Provinces. Frequency of citation, Mention index, and Fidelity level of each indigo-paste quality criterion were calculated to determine the most commonly used, most recognized, and most important quality criterion. To explore the characteristics and material basis of such traditional knowledge, we analyzed 21 samples we collected by using HPLC, pH and particle size analysis methods.Results: Local people possess unique knowledge to identify natural indigo. After thousands of years, they finally chose four criteria (color, taste, touch, and dyeing ability) and based on this, the nature indigo was divided into five quality grades. The best folk criterion was as following: dark blue with purple-red luster, smooth and difficult to wipe off; it should have a "sweet" or "spicy" taste, and dye cloth easily. It found that the higher the indigo and indirubin contents, especially indirubin content, the better the quality of the indigo paste. Within the 9-12 range, pH of high quality indigo-paste was lower. However, there was no significance difference between particle size and quality.Conclusion: The ancient methods used by the local people for identifying natural indigo are comprehensive and unique. This study revealed the importance of indirubin and pH for assessing the quality of indigo paste by documenting the various folk quality criteria and quantitative experiments. These findings differ from existing synthetic indigo-quality standards. Amid rapid modernization, traditional knowledge remains invaluable in world heritage of humanity that warrants preservation.