bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toehold Switch-Based Genetic Modulator for Tuning of Riboswitch Sensor
Authors: Hwang Yunhee , Kim Seong Gyeong , Jang Sungho , Kim Jongmin , Jung Gyoo Yeol 
Published: April 2020

Abstract
BackgroundSynthetic biological circuits are widely utilized to control microbial cell functions. Natural and synthetic riboswitches are attractive classes of sensor modules for use in synthetic biological applications. However, tuning the dose-response parameters of riboswitch circuits is challenging because considerable understanding of riboswitch mechanism and screening of mutant libraries are generally required. Therefore, novel molecular parts and strategies for controlling the dose-response parameters of riboswitch circuits are needed.ResultsHere, we developed a toehold switch-based genetic modulator that combines a previously reported hybrid input construct, which consists of riboswitch and transcriptional repressor, and de-novo-designed riboregulators named as toehold switches. First, the introduction of a pair of toehold switch and trigger as a downstream signal-processing module resulted in a functional riboswitch circuit. Next, several optimization strategies that focused on the stoichiometric ratio of RNA components greatly improved the fold-change. Finally, further characterizations confirmed low leakiness and high orthogonality for multiple toehold switches, indicating its applicability in riboswitch circuits in a seamless manner.ConclusionsThe toehold switch-based genetic modulator improved the dynamic range and dramatically shifted the operational range compared to the previous sensors only with hybrid input construct. The programmable RNA-RNA interactions amenable to in silico design and optimization can facilitate further development of RNA-based genetic modulators for flexible tuning of riboswitch circuitry and synthetic biosensors.
Enhanced Sensitivity of VEGF Detection Using Catalase-Mediated Chemiluminescence Immunoassay Based on CdTe QD/H2O2 System
Authors: Ghavamipour Fahimeh , Rahmani Hossein , Shanehsaz Maryam , Khajeh Khosro , Mirshahi Manouchehr , Sajedi Reza 
Published: April 2020

Abstract
Background
Since vascular endothelial growth factor (VEGF) is a major regulator of cancer angiogenesis, it is essential to develop a technology for its sensitive detection. Herein, we sensitized a chemiluminescence (CL) immunoassay through the combination of H2O2-sensitive TGA-CdTe quantum dot (QD) as signal transduction, dextran system as a cross-linker to prepare enzyme-labeled antigen and the ultrahigh bioactivity of catalase (CAT) as reporter enzyme.
Results
Under the optimized experimental conditions, the CL-ELISA method can detect VEGF in the excellent linear range of 2–35000 pg mL− 1, with a detection limit (S/N = 3) of 0.5 pg mL− 1 which was approximately 10 times lower than the commercial colorimetric immunoassay. This proposed method has been successfully applied to the clinical determination of VEGF in the human serum samples and the results illustrated the excellent correlation with the conventional ELISA method (R2 = 0.997). The suitable recovery rate of the method in the serum ranged from 97–107%, with a relative standard deviation of 1.2–13.4%.
Conclusions
The novel immunoassay proposes a highly sensitive, specific and stable method for very low levels detection of VEGF that can be used in primary diagnosis of tumor. With the well-designed sensing platform, this approach has a broad potential to be applied for quantitative analysis of numerous disease-related protein biomarkers for which antibodies are available.
Analysis of differential gene expression between right-sided and left-sided colon cancer by bioinformatics analysis
Authors: Chi Qiangwei , Chen Shizuan , Li Shaotang 
Published: April 2020

Abstract
Background

Colon cancer is a common tumor of the digestive tract worldwide. Recent researches have revealed that colon cancer exhibits distinct differences in clinical and biological characteristics depending on the location of the tumor. However, the underlying genetic and molecular mechanism of the differences between right-sided colon cancer (RCC) and left-sided colon cancer (LCC) are not fully understood. This study aimed to identify molecular potential biomarkers and therapeutic targets for precise treatment of right-sided and left-sided colon cancer using bioinformatics analysis.
Methods

The gene microarray profile, named GSE44076, from the Gene Expression Omnibus (GEO) public database was downloaded and processed to then select differentially expressed genes (DEGs) on the base of two sample groups of RCC and LCC. Also, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, protein–protein interaction (PPI) network construction, module analysis, validation of hub genes, and survival analysis.
Results

Finally, we obtained 2259 DEGs between RCC and LCC, 1300 of which were upregulated in RCC and 945 of which were upregulated in LCC. The results of GO and KEGG analysis of the DEGs indicated that the biological functions of DEGs in RCC and LCC were significantly different. CTLA4, IL10, IL2RB, IFNG, NCAM1, EGFR, MYC, SRC, CUL3, and NCBP2 were identified from the PPI networks as the hub genes of RCC and LCC. Among the hub genes, the log-rank tests for overall survival (OS) and disease free survival (DFS) were applied. Moreover, all hub genes, except CUL3, had differential expression levels of miRNA between tumor group and normal group.
Conclusion

These hub genes and pathways identified based on bioinformatics analysis might conduce to explain the differences between RCC and LCC, and most of the hub genes were specific to the malignant tissues. Notably, these hub genes, especially the genes associated with immunotherapy such as CTLA4, might be potential specific targets or prognostic markers for precise treatment of colon cancer.
Identification of potential significant genes in HBV related hepatocellular carcinoma via bioinformatical analysis
Authors: Zhuang Yuan , Guan Yuanyue , Sun Bin , Ouyang Yabo , Liu Xiaoni , Chen Dexi , Wang Yanjun 
Published: April 2020

Abstract
Background: The mortality rate of hepatocellular carcinoma（HCC）is the third highest worldwide. Infection with hepatitis B virus (HBV）is an important risk factor for the development of HCC. The fact that there is no available target drug for the HCC highlights the necessity to further explore its underlying mechanism.Methods: Gene expression profiles of GSE121248, GSE55092 and GSE62232 were accessible from GEO database. From 129 HCC tissues and 138 normal tissues in the three profile datasets, we picked out differentially expressed genes (DEGs) using GEO2R and Venn diagram software，analyzed Gene and Genome (KEGG) pathway and gene ontology (GO) in DEGs through DAVID software, and simulated the interactions between DEGs using the plotting function of STRING database, as well as constructed a protein-protein interaction (PPI) network by Cytoscape software Consequently significant genes with potential poor prognosis were selected using UALCAN and validated in Gene Expression Profiling Interactive Analysis.Results: In total of 103 DEGs in the three datasets, there were 26 up-regulated genes rich in regulation of attachment of spindle microtubules to kinetochore, protein localization to kinetochore, mitotic cytokinesis, cytokinesis, positive regulation of cytokinesis, Cell cycle and p53 signaling pathway while 77 down-regulated genes enriched in Retinol metabolism, Caffeine metabolism, Drug metabolism - cytochrome P450, Metabolism of xenobiotics by cytochrome P450, Chemical carcinogenesis, oxidation-reduction process, exogenous drug catabolic process, xenobiotic metabolic process, monocarboxylic acid metabolic process, epoxygenase P450 pathway and drug metabolic process. PPI network analyzed by Molecular Complex Detection (MCODE) plug-in, we found 14 hub genes including TOP2A, CCNB1, RACGAP1, DTL, PBK, NEK2, PRC1, CDK1, RRM2, BUB1B, ECT2, ANLN, HMMR, ASPM, among which demonstrated 13 genes (except PRC1) had a significantly worse prognosis based on UALCAN analysis. All of the 13 genes were highly expressed in HBV related HCC tissues compared to normal tissues through GEPIA analysis. Conclusion: The significant up-regulated DEGs found by using integrated bioinformatical methods could be potential therapeutic targets for HBV related HCC patients.
Impact of postoperative complications on long-term survival of gastric cancer patients: results from a high-volume institution in China
Authors: Pang Hua-Yang , Wang Hui , Zhao Lin-Yong , Chen Xiao-Long , Liu Kai , Zhang Wei-Han , Yang Kun , Chen Xin-Zu , Hu Jian-Kun 
Published: April 2020

Abstract
BackgroundThis study was aimed to evaluate the impact of postoperative complications (POCs) on long-term survival for gastric cancer (GC) patients with curative resection.MethodsFrom January 2009 to December 2014, a total of 1667 GC patients with curative gastrectomy were analyzed. Patients with any complications Clavien–Dindo (CD) grade II or higher were divided into complication group. Independent risk factors for the development of POCs and the relationship between POCs and long-term survival (excluding death within 90 days after surgery) were analyzed.ResultsOverall POCs CD ≥ 2 were diagnosed in 285 (17.10%) patients including infectious complications (ICs) in 231 (13.9%) and noninfectious complications (NICs) in 78 (4.68%) patients. Age ≥ 65 (P = 0.003), presence of comorbidity (P = 0.019), extensive lymphadenectomy (P = 0.027) and perioperative blood transfusion (P = 0.040) were independent risk factors of POCs. Multivariate analysis identified that presence of POCs (P < 0.001) was an independent prognostic factor and further analysis by complication type demonstrated that the deteriorated overall survival was mainly caused by ICs (P = 0.007) rather than NICs (P = 0.075), moreover, among all complications, pulmonary infection (P < 0.001) was the only significant prognostic factor.ConclusionPOCs may be an independent prognostic factor for long-term survival of GC patients and the risk is mainly driven by ICs, particular pulmonary infection.
A Unet-based Research on the Multi-Output Convolution Neural Network's Ability of Decreasing Mis-identification: Automatic Segmentation of Organs at Risk in Thorax
Authors: Zhang Jie , Yang Yiwei , Shao Kainan , Bai Xue , Fang Min , Shan Guoping , Chen Ming 
Published: April 2020

Abstract
Background

To study a multi-output convolution neural network (CNN)’s capability of reducing mis-identification.
Material and Methods

To guarantee that the CNN’s output number was the only experiment variable, we used Unet as research object. By modifying it into a multi-output (MO) one, we got a MO-Unet and the conventional single-output Unet (SO-Uent) as a comparing object. All images involved in this study were computed tomography (CT) scans coming from 105 patients with thoracic tumor. 3 organs at risk (OARs), i.e. lung, heart and spinal cord, were delineated by experienced radiation oncologists and were used as ground truth. The two models were both trained with 1240 CTs (856 images for learning and 384 images for monitor) and under the same learning settings. They were both tested on other 886 images. Dice and mis-identification pixels’ number(n) were 2 metrics for evaluation.
Results

MO-Unet and SO-Unet achieved Dice of 0.9400 ± 0.0612 (average ± standard deviation) and 0.9451 ± 0.0618 for lung, 0.9143 ± 0.1119 and 0.9160 ± 0.1071 for heart, 0.8988 ± 0.0657 and 0.9020 ± 0.0624 for spinal cord respectively. The two models’ all average Dices were ≤ 0.005. For the normalized number of cases with n = 0, MO-Unet and SO-Unet had 97.29% and 96.84% for spinal cord, 88.49% and 90.86% for heart, 81.26% and 77.09% for lung respectively. Compared to SO-Unet, the mis-identification cases of MO-Unet mainly felled in the range of small n.
Conclusions

The Dice results showed that the two models had comparable overlap. The n results suggested that the MO-Unet was better in decreasing mis-identification. Besides, a MO network is light-weighted to implement more delineation under the same computing source. Therefore, a MO network is promising in segmenting OARs and has the potential for a widespread application in China.
DAB2IP predicts treatment response and prognosis of ESCC patients and modulates its radiosensitivity through enhancing IR-induced activation of the ASK1-JNK pathway
Authors: Li Yue , Xu Meng , Fang Weiyang , Chen Xiangcun , Xu Jifei , Xiao Liang , Pan Shuhao , Sheng Lei , Pan Huaguang , Chai Huiping , Zha Tianqi , Zhao Lei , Wang Fan , Xie Dan , Liang Chaozhao , Tong Zhuting 
Published: April 2020

Abstract
Background: Disabled homolog 2 interacting protein (DAB2IP) plays a tumor-suppressive role in several types of human cancers. However, the molecular status and function of the DAB2IP gene in esophageal squamous cell carcinoma (ESCC) is rarely reported. Methods: We examined the expression dynamics of DAB2IP by immunohistochemistry (IHC) in 140 ESCC patients treated with definite chemoradiotherapy. A series of in vivo and in vitro experiments were performed to elucidate the effect of DAB2IP on the chemoradiotherapy (CRT) response and its underlying mechanisms in ESCC. Results: Decreased expression of DAB2IP in ESCCs correlated positively with ESCC resistance to CRT and was a strong and independent predictor for short disease-specific survival (DSS) of ESCC patients. Furthermore, the therapeutic sensitivity of CRT was substantially increased by ectopic overexpression of DAB2IP in ESCC cells. In addition, knockdown of DAB2IP dramatically enhanced resistance to CRT in ESCC. Finally, we demonstrated that DAB2IP regulates ESCC cell radiosensitivity through enhancing ionizing radiation (IR)-induced activation of the ASK1-JNK signaling pathway. Conclusions: Our data highlight the molecular etiology and clinical significance of DAB2IP in ESCC, which may represent a new therapeutic strategy to improve therapy and survival for ESCC patients. Keywords: Esophageal squamous cell carcinoma; DAB2IP; chemoradiosensitivity; ASK1; JNK
Clinical analysis of 17 deaths associated with the 2019 novel coronavirus
Authors: zhang cheng , Hong Dandan , Chen Wenyue , Ren Qingling , Guan Qun 
Published: April 2020

Abstract
Background Since the end of December 2019, a pneumonia outbreak has occurred in Wuhan, Hubei Province, China. An epidemiological survey showed that the pneumovirus infection was closely related to the Huanan Seafood Wholesale Market in Wuhan, causing great panic among the general population. Through the isolation and whole-genome sequencing of the pneumovirus, an infection model of the pneumovirus in human airway epithelial cells was established, and the pneumovirus was identified as the 2019 novel coronavirus (2019-nCoV), which belongs to the β-coronavirus genus. This study focus on lethiferous processes of infections associated with the new virus.Methods The data of 17 deaths from 13 hospitals in Wuhan were obtained, and the initial symptoms, clinical features during the progression of the disease, and treatment processes were well analyzed. Results At the early phase of the outbreak of 2019-nCoV, the lack of effective drugs for pneumonia caused by the new coronavirus has led to lethal results in people who are often elderly with multiple diseases. Males were affected more than females. Fever, dry coughing, shortness of breath are the primary presentations, but not all. Chest images showed viral pneumonia. Symptomatic supportive treatment did not improve respiratory distress, leading to a sudden deterioration in the condition. The development of diseases are different from the other two cronoviruses.Conclusions Older people are at high risk of death due to 2019-nCoV infection, and protecting high-risk groups is an effective way to reduce the number of deaths. A large number of viral pneumonia in Wuhan within a short period of time suggest the outbreak caused by a new virus, virus nucleic acid test will make accurate diagnosis, and the diagnosis based on clinical manifestations and imaging results provides a basis for early treatments.
Overexpression of AGAMOUS-like gene PfAG5 promote early flowering in Polypogon fugax
Authors: Zhou Fengyan , Yu Qin , Zhang Yong , Yao Chuan-Chun , Han Yun-Jing , Shen Yan 
Published: April 2020

Abstract
Background: Herbicides are the major tool for controlling large populations of yield depleting weeds. However, overreliance on herbicides has resulted in weed adaptation and herbicide resistance. In recent years, early flowering weed species related to herbicide resistance is emerging, which may cause seed loss before crop harvest, creating a new problem for non-chemical weed management. However, mechanisms regulating early flowering in weedy species is rarely investigated. Results: The MADS-box gene family plays an important role in flowering time regulation and floral organogenesis. In this study, a homolog gene of AGAMOUS sub-family (referred to as PfAG5) of the MADS-box family was cloned from plants of an early flowering Polypogon fugax population resistant to the ACCase inhibitor herbicide (clodinafop-propargyl). The PfAG5 gene was functionally characterized in Arabidopsis thaliana. Over-expression of the PfAG5 gene in Arabidopsis resulted in early flowering with abnormal flowers (e.g. small petals, short plants and reduced seed set) compared to the wild type. The expression of the PfAG5 gene was high in leaves and flowers, but low in pods in transgenic Arabidopsis. The PfAG5 gene was earlier and higher expressed in the resistant (R) than the susceptible (S) P. fugax plants. Furthermore, one protein (FRIGIDA-like protein) interacting with PfAG5 in R P. fugax was identified by the yeast two-hybrid system with relevance to flowering time regulation. Conclusions: These results suggest that the PfAG5 gene is prominently involved in modulating early flowering in P. fugax. This study provides the first evidence for the regulation mechanism of early flowering in an herbicide resistant weed species.
Musculoskeletal pain management in the emergency department
Authors: Seremeti Kyriaki , Vasilopoulos Georgios , Toylia Georgia , Kadda Olga , Kourousi Evangelia , Karimali Dimitra , Kalogianni Antonia 
Published: April 2020

Abstract
Introduction: The intensity of acute musculoskeletal pain is underestimated by health providers. Analgesia in adults that receive treatment for acute musculoskeletal pain varies from 11-29%. The timely and effective treatment of pain should become priority for the adequate pain management.Aim: The aim of the present study was to explore musculoskeletal pain management in the emergency department (ED).Material and Method: This is a descriptive study. The studied sample consisted of 82 patients, who admitted in the ED of Athen’s general hospital, due to acute musculoskeletal pain. For data collection, a special designed registration form was used. Related measurements were completed at two time points; the first time point was during patients’ admission to ED and the second one, 30 minutes post treatment or post ED discharge.Results: Patients average pain score was 7.25 ± 1.85 (first time point) and 3.76 ± 2.66 (second time point). Analgesia was provided to 51.2% of the sample and non-invasive methods were used in 51.2%. As for the frequency of the administrated drugs, analgesics were mostly preferred (29.3%), nonsteroidal anti-inflammatory drugs (NSAIDs) at 25.6% and opioids were used only at 9.8%. The mean time to first anministrated analgesic therapy was 16.56 ± 32.89 min.Conclusions: In spite of the extensive research and international guidelines for pain management, the fulfillment of the patients’ expectations for adequate and timely relief remains a challenge. The key for successful pain management lies to further education of medical stuff.
A proteomic model of SARS-COV2 infection by comparing the interactomes of BRD4 with BET-inhibition and SARS-COV2 viral proteins – implications for re-purposing approved drugs or ubiquitin-mediated degradation of select candidates
Authors: NALLUR GIRISH 
Published: April 2020

Abstract
The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected 2,029,930 people worldwide and caused 136,320 deaths. Consequently, the hunt for drugs showing efficacy against this deadly disease, or vaccines for prevention, are being intensely investigated. Unfortunately, there is a scarcity of research data on the molecular mechanisms of SARS-CoV-2 infection for quickly finding effective therapies, or repurposing existing drugs approved by the US FDA. This report models existing knowledge of SARS-COV2 viral proteins and the cellular proteins they interact with by comparisons with BRD4 interacting proteins identified from B cells, with or without BET inhibition. The E protein of SARS-COV2 interacts with BRD4, and the Spike (S) protein with CANX. Extensive similarities were observed with published cellular interactants of 13 SARS-COV2 proteins resulting in 47 BRD4-interacting protein candidates, with or without BET inhibition. 61 cellular protein targets and 132 FDA approved drugs which use these proteins as targets are proposed, which can be investigated for efficacy against SARS-COV2 infections. The implications to SARS-COV2 disease diagnosis, therapy and vaccine creation are discussed.
A SARS-CoV-2 surrogate virus neutralization test (sVNT) based on antibody-mediated blockage of ACE2-spike (RBD) protein-protein interaction
Authors: Tan Chee Wah , Chia Wan Ni , Chen Mark I-C , Hu Zhiliang , Young Barnaby E. , Tan Yee-Joo , Yi Yongxiang , Lye David C. , Anderson Danielle E. , Wang Lin-Fa 
Published: April 2020

Abstract
At this critical moment of the international response to the COVID-19 outbreak, there is an urgent need for a robust serological test to detect neutralizing antibodies to SARS-CoV-2. Such a test is not only important for contact tracing, but for determining infection rate, herd immunity and predicted humoral protection. The current gold standard is a virus neuralization test (VNT) requiring live virus and a biosafety level 3 (BSL3) laboratory. On the other hand, the ELISA- or lateral flow-based assays are for the detection of binding antibodies, which does not directly correlate with their neutralizing ability. Here we report a SARS-CoV-2 surrogate virus neutralization test (sVNT) that is designed to detect total neutralizing antibodies in an isotype- and species-independent manner. Our simple and rapid test is based on antibody-mediated blockage of virus-host interaction between the ACE2 receptor protein and the receptor binding domain (RBD) of the viral spike protein. The test has been validated with two COVID-19 patient cohorts in two different countries, achieving 100% specificity and 95-100% sensitivity and is capable of differentiating antibody responses from other known human coronaviruses. Importantly, the sVNT does not require BSL3 containment, thereby making the test immediately accessible to the global community.