bluuebunny/crossref_metadata_2025 huggingface dataset:
BRAF mutant colorectal cancer: ErbB2 expression levels as predictive factor for the response to combined BRAFi/ErbB1 inhibitors
Authors: Miele Evelina , Abballe Luana , Spinelli Gian Paolo , Besharat Zein Mersini , Catanzaro Giuseppina , Chiacchiarini Martina , Vacca Alessandra , Po Agnese , Capalbo Carlo , Ferretti Elisabetta
Published: December 2019

Background: Colorectal cancer (CRC) is a heterogeneous disease with a complex biology and has a wide number of altered genes such as BRAF, KRAS and PIK3CA. Advances with new-targeted therapies have been achieved and available treating options have prolonged patient’s survival. However, BRAF-mutated CRC patients remain unresponsive to available therapies with RAF inhibitors (RAFi) alone or combined with ErbB inhibitors (ErbBi). These unmet needs require further exploitation of oncogenic signaling in order to set up individualized treatments. Methods: To this end, we tested the efficacy of single agent or combined treatments using the BRAFi, vemurafenib and two different ErbBi: panitumumab and afatinib in CRC cells characterized by different molecular phenotypes. Results: Combination strategies with BRAFi and ErbBi achieved a better response in BRAF V600E mutated cells expressing high levels of ErbB2. Conclusions: In conclusion our findings allow us to indicate that high ErbB2 expression levels is a positive predictor factor since those patients are responsive to BRAFi/ErbBi combination.
Progression of Endothelial Dysfunction, Atherosclerosis, and Arterial Stiffness in Stable Kidney Transplant Patients: A Pilot Study
Authors: Junarta Joey , Hojs Nina , Ramphul Robin , Lowe-Jones Racquel , Kaski Juan C , Banerjee Debasish
Published: December 2019

Background: Kidney transplant patients suffer from vascular abnormalities and high cardiovascular event rates, despite initial improvements post-transplantation. The nature of the progression of vascular abnormalities in the longer term is unknown. This pilot study investigated changes in vascular abnormalities over time in stable kidney transplant patients long after transplantation. Methods: Brachial artery flow-mediated dilation (FMD), nitroglycerin-mediated dilation, carotid-femoral pulse wave velocity (cf-PWV), ankle-brachial pressure index, and common carotid artery intima-media thickness (CCA-IMT) were assessed in 18 kidney transplant patients and 17 controls at baseline and 3-6 months after. Results: There was no difference in age (51±13 vs. 46±11; P=0.19), body mass index (26±5 vs. 25±3; P=0.49), serum cholesterol (4.54±0.96 vs. 5.14±1.13; P=0.10), systolic blood pressure (BP) (132±12 vs. 126±12; P=0.13), diastolic BP (82±9 vs. 77±8; P=0.10), or diabetes status (3 vs. 0; P=0.08) between transplant patients and controls. No difference existed in vascular markers between patients and controls at baseline. In transplant patients, FMD decreased (-1.52±2.74; P=0.03), cf-PWV increased (0.62±1.06; P=0.03), and CCA-IMT increased (0.35±0.53; P=0.02). No changes were observed in controls. Conclusion: Markers of vascular structure and function worsen in the post-transplant period on long-term follow-up, which may explain the continued high cardiovascular event rates in this population. Key words: Endothelial function, arterial stiffness, atherosclerosis, kidney transplantation
Preferences for HIV testing services among young people in Nigeria
Authors: Nwaozuru Ucheoma , juliet iwelunmor , Ong Jason J. , Salah Sawsan , Obiezu-Umeh Chisom , Ezechi Oliver , Tucker Joseph D.
Published: December 2019

Background Despite high HIV incidence rates among young people in Nigeria, less than 24% of this population have ever tested for HIV. These low HIV testing rates suggest that current testing services may not align with their testing preferences. To address this gap, the objective of this study was to assess preferences for HIV testing options among young people in Nigeria.Methods We conducted a cross-sectional study using survey to assess preferences for HIV testing options among 113 youth aged 14-24 years residing in Nigeria. The survey included a series of hypothetical HIV testing options, comprised of six characteristics centered around HIV testing service (i.e. location of testing, test administrator, mode of pre-test, mode of post-test counseling, type of HIV test, and cost of HIV test). For each characteristic, participants were asked to select one of the options that they prefer or indicate none of the above. A descriptive analysis of the preferences made by participants was conducted, summarizing proportions of participants who selected different options for HIV testing.Results The mean age of study participants was 19.5 years old (SD=2.7). Most youth (73, 64.6%) had at least a secondary school degree. There was pronounced heterogeneity in HIV testing preferences among young people. Although most youth preferred free HIV testing, 14 (16.7%) reported preferring paying a small amount compared to free testing. More youth preferred blood-based HIV self-testing 39(48.8%) compared to facility-based HIV testing and oral HIV self-testing.Conclusions Our finding suggest that young people have a range of HIV testing preferences in Nigeria. This suggests that a “one-size-fits-all” approach to delivering services to youth may be challenging in this context. HIV testing services can be optimized to reach young people if a variety options are provided to meet their unique preferences.
Regional differences in reasons for consultation and general practitioners’ spectrum of services in Northern Germany – Results of a cross-sectional observational study
Authors: Schäfer Ingmar , Hansen Heike , Ruppel Thomas , Lühmann Dagmar , Wagner Hans-Otto , Kazek Agata , Scherer Martin
Published: December 2019

Background
Among other factors, the patients’ consultation reasons and GPs’ spectrum of services determine the process and outcome of the medical treatment. So far, however, there has been little information on differences in reasons for consultation and GPs’ services between urban and rural areas. Our study’s goal was thus to investigate these factors in relation to the regional location of GPs’ practices.

Methods
We conducted a cross-sectional observational study based on standardised GP interviews in a quota sampling design. All counties and independent cities within a radius of 120 km around Hamburg were divided into three regional categories (urban area, environs, rural area) and stratified proportionally to the population size. Differences in the number of reasons for consultation and services were analysed by multivariate linear regressions in mixed models adjusted for random effects on the levels of the German federal states and administrative districts. Differences in individual consultation reasons and services were identified by logistic regression via stepwise forward and backward selection.

Results
Primary care practices in 34 of the 37 selected administrative districts (91.9%) were represented in the dataset. In total, 211 GPs were personally interviewed. On average, GPs saw 344 patients per month with a slightly higher number of patients in rural areas. They reported 59.1 ± 15.4 different reasons for consultation and 30.3 + 3.9 different services. There was no statistically significant regional variation in the number of different consultation reasons, but there was a broader service spectrum by rural GPs (ß=-1.42; 95% confidence interval -2.75/-0.08; p=0.038) which was statistically explained by a higher level of medical training. Additionally, there were differences in the frequency of individual consultation reasons and services between rural and urban areas.

Conclusion
GPs in rural areas performed more frequently services usually provided by medical specialists in urban areas. This might be caused by a low availability of specialists in rural areas. The association between medical training and service spectrum might imply that GPs compensate the specific needs of their patients by completing advanced medical training before or after setting up a medical practice.

Trial registration
The study was registered in ClinicalTrials.gov (NCT02558322).
Ubiquitin-specific protease 44 inhibits cell proliferation and migration via inhibition of JNK pathway in clear cell renal cell cancer
Authors: Zhou Jiangqiao , Wang Tianyu , Qiu Tao , Chen Zhongbao , Ma Xiaoxiong , Zhang Long , Zou Jilin
Published: December 2019

Background: Clear cell renal cell carcinoma (ccRCC) is the most common form of adult kidney cancer. USP44 has been reported to be involved in various cancers. This study aimed to investigate the function role and molecular mechanism of USP44 in ccRCC. Methods: Data obtained from TCGA data portal and GSO database were analyzed to uncover the clinical relevance of USP44 expression and tumor development. The function of USP44 in cell proliferation and migration was assessed by cellular and molecular analysis. Results: USP44 was lowly expressed in the ccRCC cancer tissues compared to the normal tissue. Further, USP44 expression was negatively correlated with tumor stage, tumor grade, and patient survival . USP44 overexpression significantly inhibited tumor cell proliferation and migration of 786-O cell as well as Caki-1 cell. In addition, USP44 overexpression also prohibited cell proliferation by up-regulating P21, down-regulating Cyclin D1 expression, and inhibited cell migration by up-regulating MMP2 and MMP9 expression. In contrast, USP44 knockdown enhances ccRCC cell proliferation and migration. Furthermore, the USP44 function in inhibiting ccRCC cell proliferation and migration is associated with the phosphorylation level of JNK. Conclusion: In summary, this study showed that USP44 may be a marker in predicting the ccRCC progression and USP44 inhibits ccRCC cell proliferation and migration dependent on the JNK pathway.
The association between individual perceptions of PM2.5 pollution and pulmonary function in Chinese middle-aged and elderly residents
Authors: Chen Qi , Zhang Jiayao , Xu Yan , Sun Hong , Ding Zhen
Published: December 2019

Background: PM2.5 pollution has become a major public health concern in urban China. Understanding the residents’ individual perceptions toward haze pollution is critical for policymaking and risk communication. However, the perceptions of middle-aged and elderly residents, who particularly vulnerable to haze pollution, are poorly understood. In this study, we aimed to explore their risk perception of haze pollution, and investigating the relationship between health status and pulmonary function parameters and risk perception. Methods: A cross-sectional study of 400 randomly sampled individuals (aged 40 to 90 years) was conducted in Wuxi, a typical PM2.5-polluted city (daily average PM2.5 concentration was 52.73 μg/m3 between 2015-2017). Each participant’s demographic and health information, individual perception and pulmonary function outcomes were collected, and linear models were employed to explore the relationship between personal characteristics and pulmonary function parameters and perception factors. Results: We found that the mean values for controllability (4.99 ± 2.78) and dread of self-risk (6.90 ± 2.45) were the lowest and the highest values, respectively, in our study. Education and average family income were positively related with all individual perception factors, while age was negatively associated. A history of respiratory disease was positively associated with all individual perception factors except controllability. Significant positive associations were observed between PEF (coefficients ranged from 0.18 to 0.22) and FEF75% (coefficients ranged from 0.18 to 0.29) with a variety of individual perception factors. Conclusions: There was a lack of concern and knowledge, weak self-protection consciousness and a strong dread of PM2.5 pollution among the middle-aged and elderly residents in Wuxi. Their individual perceptions were associated with age, education levels, average family income, history of respiratory disease and pulmonary function indexes PEF and FEF75%. Our findings may help policymakers develop effective policies and communication strategies to mitigate the hazards of haze among older residents.
Yellow nutsedge WRI3/4-like gene improves drought tolerance in Arabidopsis thaliana by promoting cuticular wax biosynthesis
Authors: Cheng Chao , Hu Shutong , Han Yun , Xia Di , Huang Bang-Lian , Wu Wenhua , Hussain Jamshaid , Zhang Xuekun , Huang Bangquan
Published: December 2019

Using RACE PCR, full length WRI1-like gene was amplified from yellow nutsedge. Conserved domain and phylogenetic analyses suggested it as WRI3/4-like gene. Tissue-specific expression data showed the highest expression in leaves, followed by roots while the lowest expression was detected in tuber. Transgenic Arabidopsis plants expressing nutsedge WRI3/4-like gene showed significantly improved tolerance to both PEG-simulated drought stress and real dehydration, compared with the wild type (WT). Under normal growth conditions, the expressions of key fatty acid biosynthesis genes was not significantly different between WT and transgenic lines, while the expressions of genes involved in cuticular wax biosynthesis was significantly higher in transgenic lines compared with the WT. The PEG-simulated drought stress did not induce any significant change in the expression of fatty acid and wax biosynthesis genes in WT plants, while the expression of fatty acid and wax biosynthesis genes was significantly increased in transgenic lines compared with WT as well as unstressed transgenic control. The expression of TAG1, the gene involved in triacylglycerol (TAG) accumulation, was significantly lower in the transgenic lines than that in the WT in normal growth conditions. Drought stress slightly decreased the expression of TAG1 in the WT, but significantly lowered it in transgenic lines compared with its unstressed transgenic control and WT. Consistent with gene expression data, the cuticular wax content in Arabidopsis leaves was significantly higher in the transgenic lines than in the WT, while the oil content was not significantly different. Our results indicated that WRI3/4-like gene from Cyperus esculentus improves drought tolerance in Arabidopsis probably by promoting cuticular wax biosynthesis and, hence, could be a valuable target for improving drought tolerance in crops through recombinant DNA technology.
Inhibition of PAR1 attenuates meningeal macrophage activation and vascular inflammation in a rat model of thrombin-induced hydrocephalus
Authors: Hao Xiaodi , Ye Xianghua , Shen Dan , Li Jiawen , Le Chensheng , Tong Lu-sha , Gao Feng
Published: December 2019

BackgroundOur previous studies demonstrated that intraventricular injection of thrombin could induce hydrocephalus. The inflammation of subarachnoid space plays a key role in hydrocephalus. As thrombin, inducing coagulation, could contribute to inflammation, its effects on subarachnoid space have not been well studied. Macrophagic dysfunction may contribute to this course. However, the mechanisms that how thrombin affects macrophage in subarachnoid space have not been illustrated. Our aim was to explore the possible role that macrophage played in thrombin-induced meningeal inflammation, and to furtherly understand its contribution during thrombin-induced hydrocephalus.MethodsThere were two parts in this study. Firstly, rats had an intraventricular injection of saline or thrombin. Secondly, rats received thrombin injection with vehicle or PAR1 antagonist treatment. Immunofluorescence staining was applied to observe the activation of meningeal macrophage and the expression of NeuN in the cortex. Meanwhile, the expression of intercellular adhesion molecule 1 (ICAM1) in meningeal vessels were tested to detect the vascular inflammation. Western blot was applied to measure the secretion of pro-inflammatory cytokines (IL-1β and IFNγ).ResultsOur results demonstrated that intraventricular injection of thrombin caused significant activation of meningeal macrophages, vascular inflammation, and neuron loss. Inhibition of PAR1 pathway attenuated the M1 polarization of meningeal macrophage, reduced the inflammatory infiltrations and prevented the neuron loss, as well as hydrocephalus after thrombin injection.ConclusionsClinically available PAR1 antagonists may offer a novel therapeutic approach candidate for the prevention or the management of inflammation in hemorrhage-induced hydrocephalus.
Food consumption frequency and perceived stress and depressive symptoms among female university students in the UAE: A cross-sectional study
Authors: Ahmad Ohoud , Sabbah Haleama Al , Smail Linda , Hermena Ehab , Ghali Rola Al
Published: December 2019

Background College students lack experience and ability to cope and adapt with their new life events which make them more prone to experience stress or depression that could affect their dietary behavior. There may be an increase or a decrease in the consumption of a certain food group under stress or depression, and the amount of food ingested in general may differ as well. These changes in eating behavior could lead to lifestyle behaviors affecting the overall health and well-being of a population. This study assessed whether perceived stress and depressive symptoms predict the frequency of consumption of specific food groups among female university students.Methods A cross-sectional study was conducted among female university students using a simple random sampling method. The response rate was 97% yielded a total number of 385 participants. The associations between stress levels and the most/least consumed food groups, and between depressive symptoms levels and the most/least consumed food groups were assessed. The questionnaire included a 12-item self-administered food frequency questionnaire, Cohen’s Perceived Stress Scale, and Beck Depression Inventory-II. The study was approved by the University Ethical Committee before data collection. One-way Analysis of Variance (ANOVA) or the independent-sample t-test were carried out to test the equality of population means across the categories of each independent variable (predictor) depending on the independent variable number of categories.Results Overall, this group of female university students fell under the mild mood disturbance category (depressive symptoms) (BDI-II) and had moderate perceived stress (PSS). Perceived stress was associated with more frequent consumption of salad/raw vegetables and cooked vegetables, and less frequent consumption of cake/cookies and meat/sausage products (p<.05). Additionally, depressive symptoms were associated with less frequent consumption of fresh fruits and more consumption of fast food/canned food and soft drinks (p<.05).Conclusions The data showed that stress and depression predicted different dietary preferences consistent with distinctions between stress and depression on human behavior. Specifically, the results revealed associations between soft drinks consumption and higher depressive symptoms, and between frequent consumption of salad/raw vegetables and cooked vegetables and higher perceived stress among this group of female university students.
Efficacy and safety of Acupuncture for Gastrointestinal Dysfunction after Laparoscopy: study protocol for a randomized controlled trial
Authors: LIU LISHA , YUAN XIULI , JIANG QUANMIN , YANG LEI , HUANG GUANGQIANG , ZHANG JINGYUAN , JING LUO , LIU XIAOYING , HUO JIAN
Published: December 2019

Background: Postoperative gastrointestinal dysfunction is one of the common complications after surgery. At present, there has no internationally recognized acupuncture program although it has a positive effect on the recovery of postoperative gastrointestinal function. In this report, we have designed a scientific trial protocol to analyze the feasibility of applying acupuncture to gastrointestinal dysfunction after laparoscopic surgery. We intend to conduct a randomized controlled trial based on this protocol to evaluate the efficacy and safety of the acupuncture for postoperative gastrointestinal dysfunction. Method / design: This study is a randomized, evaluator blinded, controlled, multi-center clinical trial, which has been designed according to the Consolidated Standards of Reporting Trials (CONSORT 2010) and the standard for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA). The subjects will be chosen from the inpatients who have undergone laparoscopic surgery of Mianyang Hospital Affiliated to Chengdu University of traditional Chinese medicine, Mianyang Third People's Hospital and Mianyang Anzhou District People's Hospital. According to the random number generated by SPSS 25.0 software, the qualified subjects will be randomly assigned to the experimental group, the control group, and the blank group. Therapies will be performed 30 minutes after operation, the experimental group will be treated with acupuncture, the control group will be treated with intravenous injection of granisetron, and the blank group will be treated with intravenous injection of physiological saline. The main outcome is the first time of flatus after operation, and the secondary outcomes are abdominal pain, abdominal distention, nausea, vomiting times, gastrointestinal hormone level, and mental state. We will also evaluate the efficacy and safety of acupuncture on the basis of the principle of good clinical practice (GCP). Discuss: This is a standardized and scientific clinical trial to evaluate the efficacy and safety of acupuncture for gastrointestinal dysfunction after laparoscopic surgery. Our goal is to provide objective evidence and improve the acupoint prescription in clinical practice, so as to promote the clinical application of this technology. Trial registration China clinical trial registration ID: CHICTR -1800016991. Registered on 6 July 2018.Discussion
A novel method based on Adaptive Periodic Segment Matrix and Singular Value Decomposition for removing EMG artifact in ECG signal
Authors: chen xieqi , Lin Jianhui , Huang Chenguang , Huang Yan , He Liu
Published: December 2019

Background: The Electrocardiogram (ECG) signals are usually used to detect and monitor human health. However, the Electromyogram (EMG) artifact also can be obtained during measurement, these make difficult for doctors in correct diagnosis. In general, the ECG signal is periodic while EMG artifact is non-stationary and has overlapped with it under the frequency domain. According to these characteristics, it is necessary to extract clean ECG signals from noisy EMG artifact signals by using the periodic separation method. Method: A novel Adaptive Periodic Segment Matrix (APSM) based on Singular Value Decomposition (SVD) is proposed for extracting clean ECG from EMG artifact. Firstly a periodic segment estimation method is proposed by obtaining an average periodic length and RR intervals constraint via envelope spectrum of the measured signal. Secondly, the R wave peaks and its position of the ECG signals are detected by these. After that, APSM with rank one is formed using R wave peaks and the calculated RR intervals constraint, Then SVD is processed on this matrix, the restructured ECG signals will be obtained by the first maximum singular value of the formed matrix. The validation of proposed method is made by applying the algorithm to ECG records from the MIT-BIH Arrhythmia Database. The zero-mean percent root-mean-square difference (PRD 1 ), Cross-correlation coefficient and output signal to noise ratio (SNR output ) have been calculated for presenting the algorithm performance by comparison with other methods. Finally two heart disease cases have been studied for P wave and ST segment detection under noisy ECG with EMG artifact.Results: The proposed methods achieved significant improvement in output signal-to-noise ratio, percentage root-mean-square differences and lead to the higher value of cross-correlation coefficient between the original (clean) ECG and the denoised ECG signal. Also, the reconstructed ECG signal can be better able to follow the trend of original (clean) ECG signal under the EMG noise. Conclusion: The proposed periodic segment estimation method can adaptively find the periodic length in ECG signal by using envelope spectrum. Also, the more strict rank one trajectory matrix has been formed in APSM by using R wave peaks and RR intervals constraint. The results show that the proposed APSM-SVD method is effective for EMG artifact removal and extracting the clean ECG signal. The R peak, P wave, QRS complex and ST segment can be preserved in the reconstructed ECG signal.
Predicting the potential distribution of the parasitic Cuscuta chinensis under global warming
Authors: Ren Zichun , Zagorchev Lyuben , Ma Junxia , Yan Ming , Li Junmin
Published: December 2019

Background: The climate is the dominant factor that affects the distribution of plants. Cusucta chinensis is a stem holoparasitic plant without leaves or roots, which develops a haustorium and sucks nutrients from host plants. The potential distribution of the parasitic plant C . chinensis has not been predicted to date. This study used Maxent modeling to predict the potential distribution of C. chinensis, based on the following six main bioclimatic variables: annual mean temperature, isothermality, temperature seasonality, precipitation seasonality, precipitation of the warmest quarter, and precipitation of the coldest quarter. Results: The optimal annual average temperature and isothermality of C. chinensis ranged from 4 to 37°C and less than 45, respectively, while the optimal temperature seasonality and precipitation seasonality ranged from 4000 to 25000 and from 50 to 130, respectively. The optimal precipitation of the warmest season ranged from 300 to 1000 mm and from 2500 to 3500 mm, while that of the coldest season was less than 20000 mm. In Asia, C. chinensis is mainly distributed at latitudes ranging from 20° to 50°. During three specific historical periods (last glacial maximum, mid-Holocene, and 1960–1990) the habitats suitable for C. chinensis were concentrated in the central, northern, southern, and eastern parts of China. From the last glacial maximum to the mid-Holocene, the total area with suitability of 0.5-1 increased by 0.0875 million km 2 ; however, from the mid-Holocene to 1960–1990, the total area with suitability of 0.5-1 decreased by 0.0759 million km 2 . The simulation results of habitat suitability in the two representative concentration pathways (RCP) 2.6 (i.e., the low greenhouse gas emissions pathway) and 8.5 (i.e., the high greenhouse gas emissions pathway) indicate that the habitat suitability of C. chinensis decreased in response to the warming climate. Compared with RCP2.6, areas with averaged suitability and highsuitability for survival (RCP8.5) decreased by 0.18 million km 2 . Conclusion: Suitable habitats of C. chinensis are situated in central, northern, southern, and eastern China. The habitat suitability of C. chinensis decreased in response to the warming climate. These results provide a reference for the management of C. chinensis.
Novel Variations at Three Different Positions of Prion Protein Coding Gene in Ethiopian Sheep Breeds and the Resistance/Susceptible Status to Classical and Atypical Scrapie
Authors: Teferedegn Eden Yitna , Yaman Yalcin , Un Cemal
Published: December 2019

Background: Classical Scrapie susceptibility in sheep has been linked to three polymorphisms at positions 136, 154, and 171 in the PRNP gene whereas atypical scrapie susceptibility is related to a polymorphism at position 141. Many other variants over the length of the prion protein coding gene were reported. Since infectious prion protein itself seems to be polymorphic, the identified novel PRNP gene variations may play a crucial role in fighting against the emergence of a new form of scrapie disease. Many studies conducted around the world to identify disease resistant status and new variants of PRNP gene in different breeds. However, such in-depth studies have never addressed the African continent’s sheep breeds. Therefore, genotyping native Ethiopian sheep breeds PRNP gene provides essential information to the current knowledge. This study aimed to identify potential novel variations in the Ethiopian sheep PRNP gene, thereby determine the uniqueness of the native breeds and predict scrapie status of sheep population based on the genotypes distribution. Results : Five novel variants were identified in the PRNP gene of native Ethiopian sheep. Four non-synonymous heterozygous substitutions at H99Q (CAC-->CAA), H99L (CAC-->CTA), A116E (GCA-->GAA), A116T (GCA-->ACA), and one synonymous N103N (AAC-->AAT) variants were detected. In addition to the novel variations, polymorphisms at 126,127,138,142,146,231, and 237 positions were also identified. The haplotype ARR was observed only in Menz and Afar breeds with frequencies 0.02 and 0.05 respectively. However, neither ARR/ARR nor VRQ/VRQ genotypes were identified in all of the breeds. Conclusion: Two of the novel variations at position 99 and 103 that are placed closer to the cleavage site and variant at 116 spotted in the palindrome region along with variants at position 127 in Glycine repeat domain may influence the conformational flexibility of prion protein. The low frequency of ARR haplotype and the sole variant 141L demonstrated that Ethiopian sheep are susceptible to classical scrapie and resistant to atypical scrapie. This study provides a valuable dataset that can be potentially integrated into selective breeding strategies against scrapie during inbreeding, crossbreeding and help to take precautious measures.
Prognostic value of an immune long non-coding RNA signature in liver hepatocellular carcinoma
Authors: kong rui , Wang Nan , Han Wei , Zheng Yuejuan , Lu Jie
Published: December 2019

Background: In recent years, long non-coding RNAs (lncRNAs) are emerging as crucial regulators in the immunological process of liver hepatocellular carcinoma (LIHC). Increasing studies have found that some lncRNAs could be used as a diagnostic or therapeutic target for clinical management, but little research has investigated the role of immune-related lncRNA in tumor prognosis. In this study, we aimed to develop an immune lncRNA signature for the precise diagnosis and prognosis of liver hepatocellular carcinoma. Methods: Gene expression profiles of LIHC samples obtained from TCGA were screened for immune-related genes using two reference gene sets. The optimal immune-related lncRNA signature was built via correlational analysis, univariate and multivariate cox analysis. Then the Kaplan-Meier plot, ROC curve, clinical analysis, gene set enrichment analysis, and principal component analysis were carried out to evaluate the capability of immune lncRNA signature as a prognostic indicator. Results: Six long non-coding RNA MSC−AS1, AC009005.1, AL117336.3, AL031985.3, AL365203.2, AC099850.3 were identified via correlation analysis and cox regression analysis considering their interactions with immune genes. Next, tumor samples were separated into two risk groups by the signature with different clinical outcomes. Stratification analysis showed the prognostic ability of this signature acted as an independent factor. The AUC value of ROC curve was 0.779. The Kaplan-Meier method was used in survival analysis and results showed a statistical difference between the two risk groups. The predictive performance of this signature was validated by principal component analysis (PCA). Data from gene set enrichment analysis (GSEA) further unveiled several potential biological processes of these biomarkers may involve in. Conclusion: In summary, the study demonstrated the potential role of the six-lncRNA signature served as an independent prognostic factor for LIHC patients.
Fusion transcript detection using spatial transcriptomics
Authors: Friedrich Stefanie , Sonnhammer Erik LL
Published: December 2019

Background: Fusion transcripts are involved in tumourigenesis and play a crucial role in tumour heterogeneity, tumour evolution and cancer treatment resistance. However, fusion transcripts have not been studied at high spatial resolution in tissue sections due to the lack of full-length transcripts with spatial information. New high-throughput technologies like spatial transcriptomics measure the transcriptome of tissue sections on almost single-cell level. While this technique does not allow for direct detection of fusion transcripts, we show that they can be inferred using the relative poly(A) tail abundance of the involved parental genes. Method: We present a new method STfusion, which uses spatial transcriptomics to infer the presence and absence of poly(A) tails. A fusion transcript lacks a poly(A) tail for the 5´ gene and has an elevated number of poly(A) tails for the 3´ gene. Its expression level is defined by the upstream promoter of the 5´ gene. STfusion measures the difference between the observed and expected number of poly(A) tails with a novel C-score. Results: We verified the STfusion ability to predict fusion transcripts on HeLa cells with known fusions. STfusion and C-sore applied to clinical prostate cancer data revealed the spatial distribution of the cis-SAGe SLC45A3-ELK4 in 12 tissue sections with almost single-cell resolution. The cis-SAGe occured in the centre or periphery of inflamed, prostatic intraepithelial neoplastic, or cancerous areas, and occasionally in normal glands. Conclusions: STfusion detects fusion transcripts in cancer cell lines and clinical data, and distinguishes chimeric transcripts from chimeras caused by trans-splicing events. With STfusion and the use of C-scores, fusion transcripts can be localised in clinical tissue sections on almost single cell level.
Metformin and endometrial cancer risk: A Meta-analysis
Authors: Xie Weimin , Wen Dan
Published: December 2019

Objective: To assess the association between metformin and endometrial cancer risk by conducting a meta-analysis.Methods: A comprehensive search of electronic databases, conference abstracts, and clinical trial registers was performed to identify available evidence. Studies that evaluated the association between metformin use and endometrial cancer risk were considered. We pooled relative risk (RR) estimates with 95% confidence intervals (CIs) by using either a fixed-effects or a random-effects model.Results: Nine studies (1 randomized controlled trial, 5 cohort studies, and 3 case-control studies) involving more than 1.20 million participants and 7,762 cases of endometrial cancer met eligibility criteria. There was no evidence of an association between metformin use and endometrial cancer risk (RR, 0.96; 95% CI, 0.80 to 1.16). Similarly, the pooled data showed that metformin use was not significantly associated with endometrial cancer risk in patients with diabetes (RR, 0.93; 95% CI, 0.78 to 1.11). In subgroup analyses, the results were stable across different study designs and comparisons, and remained unchanged after adjusting for age and BMI or obesity.Conclusions: The current meta-analysis suggests that metformin has no chemopreventive effect against endometrial cancer.
The Promise of Whole-Exome Sequencing in Detecting Novel Variants of the MYO15A Gene in Two Iranian Pedigrees with Non-Syndromic Hearing Loss, A descriptive experimental study
Authors: khatami somayeh , Askari Masomeh , Bahreini Fatemeh , Chaleshtori Morteza Hashemzadeh , Asgharzadeh Samira
Published: December 2019

Background: Clinical genetic diagnosis of non-syndromic hearing loss (NSHL) is quite challenging. With regard to its high heterogeneity as well as large size of some genes, it is also really difficult to detect causative mutations using traditional approaches. One of the recent technologies called whole-exome sequencing (WES) has been thus developed in this domain to remove the limitations of conventional methods.Methods: This study was a report on two unrelated pedigrees with multiple affected cases of hearing loss (HL). Accordingly, clinical evaluations and genetic analysis were performed in both families.Results: The implementation of WES to uncover autosomal recessive non-syndromic hearing loss (ARNSHL) and its related variants was reported in the present study. Two novel variants of MYO15A i.e. c.T6442A:p.W2148R and c.10504dupT:p.C3502Lfs*15 were correspondingly identified and then segregations were confirmed using Sanger sequencing. According to online prediction tools, both identified variants seemed to have damaging effects.Conclusion: This study further supported the effectiveness of WES for genetic diagnosis of ARNSHL as a first approach.
Association analysis of miRNA-related genetic polymorphisms in miR-143/145 and KRAS with colorectal cancer susceptibility and survival
Authors: Wang Danyang , Liu Qingmin , Ren Yanjun , Zhang Yan , Wang Xin , LIU BING
Published: December 2019

Background MicroRNAs have important roles in tumorigenesis. There is accumulating evidence of aberrant expression of miR-143 and miR-145 and their target gene KRAS has been described in colorectal cancer (CRC). We hypothesize that single nucleotide polymorphisms (SNPs) within or near mRNA-miRNA binding sites may affect miRNA/target gene interaction, resulting in differential mRNA/protein expression and promoting the development and progression of CRC.Methods We conducted a case-control study of 507 CRC cases recruited from a tertiary hospital and 497 population-based controls to assess the association of genetic polymorphisms in miR-143/145 and the KRAS 3′ untranslated region (3′ UTR) with CRC susceptibility and survival. Deaths and causes of death among the CRC cases were identified using the Hangzhou Cancer Registration System and Death Surveillance System. Genetic variations of genomic regions located from 500 bp upstream to 500 bp downstream of the miR-143/miR-145 gene and the 3′ UTR of KRAS were selected using the Haploview and HaploReg software. Results Using publicly available expression profiling data, we found that miR-143/145 and KRAS expression were all reduced in rectal cancer tissue compared with adjacent normal mucosa. The Rs74693964 C/T variant located 65 bp downstream of miR-145 genomic regions was observed to be associated with CRC susceptibility (adjusted odds ratio 2.414, 95% CI: 1.385–4.206). Among non-smokers, the miR-143 rs41291957 GA genotype and miR-145 rs74693964 CT genotype were borderline significantly associated with an increased risk of rectal cancer. However, there was no interaction effect between selected SNPs and smoking status. Cumulative effects of miR-143 and miR-145 on CRC risk were observed (Ptrend=0.03). CRC cases carrying variant genotype TT of KRAS rs712 had poorer survival (log-rank P=0.044, adjusted hazard ratio 4.328, 95% CI: 1.236–15.147). Conclusions Our results indicate that miRNA-related polymorphisms in miR-143/145 and KRAS are likely to be deleterious and represent potential biomarkers for CRC susceptibility and survival.
Precise annotation of tick mitochondrial genomes reveals multiple copy number variation of short tandem repeats and one transposon-like element
Authors: Chen Ze , Xu Xiaofeng , Yang Xiaolong , Yu Zhijun , Barker Stephen C. , Kelava Samuel , Chen Defu , Bu Wenjun , Liu Jingze , Gao Shan
Published: December 2019

Background: Annotation of mitochondrial (mt) genomes is indispensable for fundamental research in many fields, including mt biochemistry, physiology, and the molecular phylogenetics and evolution of animals. Moreover, high-resolution annotation of animal mt genomes can be used to investigate RNA processing, maturation, degradation, and even the regulation of gene expression. In this study, we used long-PCR amplification combined with Next-Generation Sequencing (NGS) to obtain complete mt genomes of individual ticks and performed precise annotation of these mt genomes. We aimed to: (1) develop a simple, cost-effective and accurate method for the study of extremely high AT-content mt genomes within an individual animal containing miniscule DNA; (2) provide a high-quality reference genome for D. silvarum with precise annotation and also for future studies of other tick mt genomes; and (3) use these mt genomes containing two Control Regions (CRs) to confirm our previous findings from those containing one CR. Results: Based on these mt genome annotations, most of our findings were consistent with those from previous studies. Moreover, two new and important findings were reported for the first time, contributing fundamental knowledge to mt biology. The first was the discovery of a transposon-like element that may eventually reveal much about mechanisms of gene rearrangements in mt genomes. Another finding was that Copy Number Variation (CNV) of Short Tandem Repeats (STRs) account for mitochondrial sequence diversity (heterogeneity) within an individual tick, insect, mouse or human. All the detected DNA variations within a single human cell were CNV of STRs, whereas SNPs were not detected. The CNV of STRs in the protein-coding genes resulted in frameshift mutations in the proteins, which can cause deleterious effects. Mitochondria containing these deleterious STR mutations accumulate in cells and could produce deleterious proteins. Conclusions: We proposed that the accumulation of CNV of STRs in mitochondria causes aging or diseases. Our study will lead to the reconsideration of the importance of STRs and a unified study of CNV of STRs with longer and shorter repeat units (particularly polynucleotides) in both nuclear and mt genomes.
Genome-wide association study (GWAS) reveals genetic loci of lead (Pb) tolerance during seedling establishment in rapeseed (Brassica napus L.)
Authors: Zhang Fugui , Xiao Xin , Xu Kun , Cheng Xi , Xie Ting , Hu Jihong , Wu Xiaoming
Published: December 2019

Background Lead (Pb) pollution in soil has become one of the major environmental threats to plant growth and human health. Safe utilization of Pb contaminated soil by phytoremediation require Pb tolerant rapeseed ( Brassica napus L.) accessions. However, breeding of new B. napus cultivars tolerance to Pb stress has been restricted by limited knowledge on molecular mechanisms involved in Pb tolerance. This work was carried out to identify genetic loci related to Pb tolerance during seedling establishment in rapeseed.Results Pb tolerance, which was assessed by quantifying radicle length (RL) under 0 or 100 mg/L Pb stress condition, shown an extensive variation in 472 worldwide-collected rapeseed accessions. Based on the criterion of relative RL>80%, six Pb tolerant genotypes were selected. Four quantitative trait loci (QTL) associated with Pb tolerance were identified by Genome-wide association study. The expression level of nine promising candidate genes, including GSTUs , BCATs , UBP13 , TBR and HIPP01 , located in these four QTL regions, were significantly higher or induced by Pb in Pb tolerant accessions in comparison to Pb sensitive accessions.Conclusion To our knowledge, this is the first study on Pb tolerant germplasms and genomic loci in B. napus . The findings can provide valuable genetic resources for the breeding of Pb tolerant B. napus cultivar and understanding of Pb tolerance mechanism in Brassica species.
Evaluation of antioxidant and antimicrobial activities of chloroformic and methanolic extracts of 6 important medicinal plants collected from Northern of Iran
Authors: Ghahari Somayeh , Hadadi Zahra , Nematzadeh Ghorban Ali
Published: December 2019

Background: The plant essential oils and extracts are possible sources of natural bioactive molecules and have been selected globally for new antimicrobial compounds, food preservatives, and alternatives to treat infectious disease.Methods: In this research, antimicrobial activities of chloroformic and methanolic extracts of Sophora flavescens, Rhaponticum repens, Alhagi maurorum, Melia azedarach, Peganum harmala, and Juncus conglomeratus were evaluated against 8 bacteria (S. aureus, B. subtilis, R. toxicus, P. aeruginosa, E. coli, P. syringae, X. campestris, P. viridiflava) and 3 fungi (Pyricularia oryzae, Fusarium oxysporum and Botrytis cinerea) through disc diffusion method. Furthermore, the essential oil of plants with the highest antibacterial activity was analyzed utilizing GC/MS. Moreover, tested plants were exposed to screening for possible antioxidant effect utilizing DPPH test, guaiacol peroxidas, and catalase enzymes. Besides, the amount of total phenol and flavonoid of these plants was measured. Results: Among tested plants, methanolic and chloroformic extracts of P. harmala fruits showed the highest antibacterial activity against tested bacteria. Also, the investigation of free radical scavenging effects of the tested plants indicated the highest DPPH, protein, guaiacol peroxidase, and catalase in P. harmala, M. azedarach, J. conglomeratus fruits, and J. conglomeratus fruits, respectively. In addition, the phytochemical analysis demonstrated the greatest amounts of total phenolic, and flavonoid compositions in J. conglomeratus and P. harmala. Conclusion: The results indicated that these plants can act as a promising antimicrobial agent due to its short killing time.
Safety assessment of cerium oxide nanoparticles: Combined repeated-dose toxicity with reproductive/developmental toxicity screening and biodistribution in rats
Authors: Lee Jinsoo , Jeong Ji-Seong , Kim Sang Yun , Lee Seung-Jin , Shin Young-Jun , Im Wan-Jung , Kim Sung-Hwan , Park Kwangsik , Jeong Eun Ju , Nam Sang-Yoon , Yu Wook-Joon
Published: December 2019

Background Cerium oxide nanoparticles (CeO 2 NPs) are widely used in various commercial applications because of their characteristic properties. CeO 2 NPs can be easily exposed to humans in real life, but the safety assessment of CeO 2 NPs has not been fully investigated. Therefore, in this study, we conducted a combined repeated-dose and reproductive/developmental toxicity screening study to investigate the potential effects on general health hazards, including reproductive/developmental functions, after repeated CeO 2 NPs oral exposure. In addition, tissues from parental animals and their pups were collected to analyze the internal accumulation of cerium. CeO 2 NPs were orally administered to Sprague-Dawley rats at doses of 0, 100, 300 and 1000 mg/kg during their pre-mating, mating, gestation and early lactation periods. Results In the general systemic and reproductive/developmental examinations, no marked toxicities were observed in any of in-life and terminal observation parameters in this study. In the biodistribution analysis, cerium was not detected in either parental or pup tissues (blood, liver, lungs and kidneys). Conclusion Repeated oral exposure of CeO 2 NPs did not induce marked toxicities affecting general systemic and reproductive/developmental functions up to the dose level of 1000 mg/kg and the CeO 2 NPs were not systemically absorbed in parental animals or their pups. This result could be used to risk assessment for human, and additional toxicity studies with CeO 2 NPs will be necessary considering various physicochemical properties and exposure probabilities of this nanoparticles.