bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the Autof MS1000 mass spectrometer in the identification of clinical isolates
Authors: ma qiong , Zhang Qi , Yuan Youhua , Yan Wenjuan , Wang Shanmei , Xu Junhong , Zhang Jiangfeng , Wang Yuming , Li Yi
Published: October 2020

Background: To evaluate the accuracy and performance of the Autof MS1000 mass spectrometer in bacteria and yeast identification, 2,342 isolates were obtained from microbial cultures of clinical specimens (e.g., blood, cerebrospinal fluid, respiratory tract samples, lumbar puncture fluid, wound samples, stool, and urine) collected in 2019 in Henan Provincial People’s Hospital. Repetitive strains from the same patient were excluded. We tested the Autof MS1000 and Bruker Biotyper mass spectrometry systems and the classical biochemical identification system VITEK 2/API 20C AUX. Inconsistencies in strain identification among the three systems were identified by 16S rDNA and gene sequencing.Results: At the species level, the Autof MS1000 and Bruker Biotyper systems had isolate identification accuracies of 98.9% and 98.5%, respectively. At the genus level, the Autof MS1000 and Bruker Biotyper systems were 99.7% and 99.4% accurate, respectively. The instruments did not significantly differ in identification accuracy at either taxonomic level. The frequencies of unreliable identification were 1.1% (26/2,342) for the Autof MS1000 and 1.5% (34/2,342) for the Bruker Biotyper. In vitro experiments demonstrated that the coincidence rate of the Autof MS1000 mass spectrometer in the identification of five types of bacteria was >93%, the identification error rate was <3%, and the no identification rate was 0. This indicates that the Autof MS1000 system is acceptable for identification.Conclusions: The Autof MS1000 mass spectrometer can be utilised to identify clinical isolates. However, an upgradation of the database is recommended to correctly identify rare strains.
Maternal syphilis treatment and pregnancy outcomes: a retrospective study in Jiangxi Province, China
Authors: Wan Zhihua , Zhang Huan , Xu Haigang , Hu Yang , Tan Cai , Tao Yuling
Published: October 2020

BackgroundStudies investigating the associations of maternal syphilis treatment with birth outcomes mainly concentrated in economically developed areas. Limited data are available in economically underdeveloped areas, such as Jiangxi Province. The study aims to investigate the impact of maternal treatment on birth outcomes in Jiangxi Province, China.MethodsData were obtained from the China’s Information System of Prevention of Mother-to-Child Transmission in Jiangxi Province. All syphilis infected pregnant women who delivered ≥28 gestational weeks and were registered in this system between 1 January 2013 and 31 December 2019 were enrolled. Pregnancy outcomes were evaluated by group-specific analyses according to their treatment status, adequacy and initiation time.Results4210 syphilis infected pregnant women were included in the analyses. Infants born to untreated mothers (n = 1364) were at significantly higher risk for stillbirth (adjusted odds ratio (aOR) = 1.74, 95% CI, 1.01-3.00, P = 0.045), preterm birth (aOR = 1.27, 95% CI, 1.02-1.59, P = 0.034) and low birth weight (LBW) (aOR = 1.44; 95% CI, 1.11-1.86, P = 0.006) than those born to treated mothers (n = 2846) after adjustment for confounding factors. A significantly higher risk of stillbirth (aOR = 3.68; 95% CI, 1.62-8.34, P = 0.002), preterm birth (aOR = 2.26; 95% CI, 1.71-3.00, P < 0.001), LBW (aOR = 2.23; 95% CI, 1.59-3.14, P < 0.001) and congenital syphilis (CS) (aOR = 3.63; 95% CI, 1.80-7.31, P < 0.001) was found in infants exposed to mothers treated inadequately (n = 1299) than those treated adequately (n = 1547). No pregnant women who initiated the treatment in the first trimester (n = 682) delivered a neonatal CS case. Compared with mothers who initiated treatment in the first trimester (n = 682), those initiated in the third trimester (n = 1234) suffered an increased risk of stillbirth (aOR = 4.48; 95% CI, 1.31-15.30, P = 0.017), preterm birth (aOR = 2.34; 95% CI, 1.61-3.40, P < 0.001) and LBW (aOR = 3.25; 95% CI, 1.97-5.37, P < 0.001). ConclusionsMaternal treatment, especially early and adequate treatment, plays a crucial role in mitigating adverse pregnancy outcomes among syphilis infected women.
­­­­­­Genomic analysis of worldwide sheep breeds reveals PDGFD as a major target of fat-tail selection in sheep
Authors: Dong Kunzhe , Yang Min , Han Jiangang , Ma Qing , Han Jilong , Song Ziyi , Luosang Cuicheng , Gorkhali Neena Amatya , Yang Bohui , He Xiaohong , Ma Yuehui , Jiang Lin
Published: October 2020

Background: Fat tail is a unique trait in sheep acquired during domestication. Several genomic analyses have been conducted in sheep breeds from limited geographic origins to identify the genetic factors underlying this trait. Nevertheless, these studies obtained different candidates. The results of these regional studies were easily biased by the breed structures. Results: To minimize the bias and distinguish the true candidates, we used an extended data set of 968 sheep representing 18 fat-tailed breeds and 14 thin-tailed breeds from around the world, and integrated two statistical tests to detect selection signatures, including Genetic Fixation Index (FST) and difference of derived allele frequency (ΔDAF). The results showed that platelet derived growth factor D (PDGFD) exhibited the highest genetic differentiation between fat- and thin-tailed sheep breeds. Analysis of sequence variation identified that a 6.8-kb region within the first intron of PDGFD is likely the target of positive selection and contains regulatory mutation(s) in fat-tailed sheep. Histological and gene expression analyses demonstrated that PDGFD expression is associated with maturation and hemostasis of adipocytes. Further retrospective analysis of public transcriptomic datasets revealed that PDGFD expression is down-regulated during adipogenesis in both human and mouse, and is higher in fat tissues of obese individuals than that in lean individuals. Conclusions: These results reveal that PDGFD is the predominant factor for the fat tail phenotype in sheep by contributing to adiopogenesis and maintaining the hemostasis of mature adipocytes. This study provides insights into the selection of fat-tailed sheep and has important application to animal breeding, as well as obesity-related human diseases.
Bioelectrical Impedance Analysis-derived Phase Angle as a Determinant of Protein-energy Wasting and Frailty in Maintenance Hemodialysis Patients: retrospective cohort study
Authors: Saitoh Masakazu , Ogawa Masumi , Kondo Hisae , Suga Kiichi , Takahashi Tetsuya , Itoh Haruki , Tabata Yoichiro
Published: October 2020

Background: Phase angle (PA), measured by bioelectrical impedance analysis (BIA) has been studied as indicator of nutritional status or muscle function in hemodialysis (HD) patients. It remains unclear if the phase angle is associated protein-energy wasting (PEW) or frailty, which are common complication in hemodialysis patients. The aim of this study is to determine whether BIA-derived PA is a marker of PEW or frailty in HD patients.Methods: This retrospective observational study included 116 adult HD patients (35% female, 64 ± 12 years of age) in a single dialysis center. Patients were classified according to the PA quartiles into four groups; 1) first quartile: PA<3.7°, 2) second quartile: PA 3.7-4.1°, 3) third quartile: PA 4.2-4.9°and 4) forth quartile: PA ≥ 5.0°. International Society of Renal Nutrition and Metabolism (ISRNM) criteria and Japanese version of Cardiovascular Health Study (J-CHS) criteria were used to identify PEW and frailty.Results: The lower PA group was associated with a greater risk of PEW (35% vs. 24% vs. 21% vs. 3%; p=0.032), frailty (59% vs. 40% vs. 21% vs. 3%; p<0.001). In multivariate logistic regression analysis, the first quartile group was at a significantly greater risk of both PEW and frailty compared with the fourth quartile group after adjusting for other confounding factors. Conclusions: Lower PA was associated with a greater risk of PEW and frailty in HD patients.
Pegylated liposomal doxorubicin in patients with epithelial ovarian cancer
Authors: Yuan Zhen , Zhang Ying , Cao Dongyan , Shen Keng , Li Qingshui , Zhang Guonan , Wu Xiaohua , Cui Manhua , Yue Ying , Cheng Wenjun , Wang Li , Qu Pengpeng , Tao Guangshi , Hou Jianqing , Sun Lixin , Meng Yuanguang , Li Guiling , Li Changzhong , Shi Huirong , Chen Yaqing
Published: October 2020

Objective: To evaluate the efficacy and safety of PLD in treating of in patients who experience epithelial ovarian, fallopian tubal, and peritoneal cancer progression within 12 months after the first-line platinum-based therapy. Methods: This was an open-label, single-arm and multicenter clinical trial. The ORR was the interim primary objective, and the DCR, AEs and QOL were the secondary objectives. The impact of factors on efficacy outcomes, the change trend of CA125 and the artificial platinum-free interval were exploratory endpoints. Results: Totally, 115 patients were enrolled in this study and included in the ITT population. Moreover, 101 patients were included in the safety population. The median follow-up time was 4 months (IQR 2–6). In the ITT population, the confirmed ORR was 37.4% (95% CI, 28.4%-46.4%), and the DCR was 65.2% (95% CI, 56.4%-74.1%). The previous response status to platinum-based chemotherapy and baseline CA125 levels were significantly correlated with the ORR. The ORR was significantly higher in patients with a CA125 decrease after the first cycle than in the patients with a CA125 increase. The most common grade 3 or higher AE was hand-foot syndrome (3 [3.0%] of 101 patients). No statistically significant differences existed between the baseline and the postbaseline questionnaires. Conclusions: For patients who experience platinum-resistant and platinum-refractory relapse, the use of PLD may be acceptable because of the associated satisfactory efficacy, low frequency of AEs and high patient QOL. Moreover, a low CA125 level at baseline and a reduction in CA125 after the first cycle are predictive factors for satisfactory efficacy.
Nonlinear ridge regression improves robustness of cell-type-specific differential expression analysis
Authors: Takeuchi Fumihiko , Kato Norihiro
Published: October 2020

Background: Epigenome-wide association studies (EWAS) and differential gene expression analyses are generally performed on tissue samples, which consist of multiple cell types. Cell-type-specific effects of a trait, such as disease, on the omics expression are of interest but difficult or costly to measure experimentally. By measuring omics data for the bulk tissue, cell type composition of a sample can be inferred statistically. Subsequently, cell-type-specific effects are estimated by linear regression that includes terms representing the interaction between the cell type proportions and the trait. This approach involves two issues, scaling and multicollinearity.Results: First, although cell composition is analyzed in linear scale, differential methylation/expression is analyzed suitably in the logit/log scale. To simultaneously analyze two scales, we applied nonlinear regression. Second, we show that the interaction terms are highly collinear, which is obstructive to ordinary regression. To cope with the multicollinearity, we applied ridge regularization. In simulated data, nonlinear ridge regression attained well-balanced sensitivity, specificity and precision. In real data, nonlinear ridge regression detected signals consistently over the examined cases.Conclusion: Nonlinear ridge regression performed cell-type-specific association test on bulk omics data more robustly than previous methods. The omicwas package for R implements nonlinear ridge regression for cell-type-specific EWAS, differential gene expression and QTL analyses. The software is freely available from https://github.com/fumi-github/omicwas
A nomogram based on pretreatment CT radiomics features for predicting complete response to chemoradiotherapy in patients with esophageal squamous cell cancer
Authors: Luo Hesan , Huang Shao-Fu , Xu Hong-Yao , Li Xu-Yuan , Wu Sheng-Xi , Wu De-Hua
Published: October 2020

Purpose: To develop and validate a nomogram model to predict complete response (CR) after concurrent chemoradiotherapy (CCRT) in esophageal squamous cell carcinoma (ESCC) patients using pretreatment CT radiomic features. Methods: Data of patients diagnosed as ESCC and treated with CCRT in Shantou Central Hospital during the period from January 2013 to December 2015 were retrospectively collected. Eligible patients were included in this study and randomize divided into a training set and a validation set after successive screening. The least absolute shrinkage and selection operator (LASSO) with logistic regression to select radiomics features calculating Rad-score in the training set. The logistic regression analysis was performed to identify the predictive clinical factors for developing a nomogram model. The area under the receiver operating characteristic curves (AUC) was used to assess the performance of the predictive nomogram model and decision curve was used to analyze the impact of the nomogram model on clinical treatment decisions. Results: A total of 226 patients were included and randomly divided into two groups, 160 patients in training set and 66 patients in validation set. After LASSO analysis, seven radiomics features were screened out to develop a radiomics signature Rad-score. The AUC of Rad-score was 0.812 (95%CI: 0.742-0.869, p<0.001) in the training set and 0.744 (95%CI: 0.632-0.851, p=0.003) in the validation set. Multivariate analysis showed that Rad-score and clinical staging were independent predictors of CR status, with P values of 0.035 and 0.023, respectively. A nomogram model incorporating Rad-socre and clinical staging was developed and validated, with an AUC of 0.844 (95％CI: 0.779-0.897) in the training set and 0.807 (95％CI: 0.691-0.894) in the validation set．Delong test showed that the nomogram model was significantly superior to the clinical staging, with P<0.001 in the training set and P=0.026 in the validation set. The decision curve showed that the nomogram model was superior to the clinical staging when the risk threshold was greater than 25%. Conclusion: We developed and validated a nomogram model for predicting CR status of ESCC patients after CCRT. The nomogram model was combined radiomics signature Rad-score and clinical staging. This model provided us with an economical and simple method for evaluating the response of chemoradiotherapy for patients with ESCC.
Use of traditional medicine for dental care by different ethnic groups in New Zealand
Authors: Guo Jun , Low Karson , Mei Li , Li JiaHui , Qu Wenwen , Guan Guangzhao
Published: October 2020

Background: There is an increasing public interest in the use of TM internationally, yet there is a paucity of research on the use of TM by the public in the dental setting. This study aimed to explore the views, use of and access to TM in dentistry among different ethnic groups residing in New Zealand.Methods: Qualitative study and in-depth interviews were used. An individual semi-structured questionnaire was used to collect data. Interviews were recorded, transcribed, and analysed using an inductive approach to identify the main themes. Results: Three main themes were extracted from interviews with 14 participants from diverse cultural backgrounds: (1) the perspectives of TM varied among different ethnic groups and included the involvement of spirituality, the environment, knowledge and usage of TM. (2) The TM that was used by different ethnic groups included plants, herbs, massage, and other forms of healing. Reasons for choosing traditional or western medicines generally included family tradition, access to TM, and finding a competent traditional healer. (3) The barriers in accessing TM included the paucity of traditional healers, difficulty accessing plants and cost, therefore most would look for a substitution or alternative treatment. Conclusion: Even though the access to these TM in New Zealand was a challenge for the majority of the participants, they are still considered the first-line treatment for the majority. This study provided dental practitioners an insight into the different sort of TM used by the population. By understanding and acknowledging the use of TM, dental practitioners could create a supportive environment for patients to disclose their use of TM and allow them to educate patients on the use of TM.
Deep learning based DNA:RNA triplex forming potential prediction
Authors: ZHANG Yu , Long Yahui , Kwoh Chee Keong
Published: October 2020

Background: Long non-coding RNAs (lncRNAs) can exert functions via forming triplex with DNA. The current methods in predicting the triplex formation mainly rely on mathematic statistic according to the base paring rules. However, these methods have two main limitations: i) they identify a large number of triplex-forming lncRNAs, but the limited number of experimentally verified triplex-forming lncRNA indicates that maybe not all of them can form triplex in practice, and ii) their predictions only consider the theoretical relationship while lacking the features from the experimentally verified data.Results: In this work, we develop an integrated program named TriplexFPP (Triplex Forming Potential Prediction), which is the first machine learning model in DNA:RNA triplex prediction. TriplexFPP predicts the most likely triplex-forming lncRNAs and DNA sites based on the experimentally verified data, where the high-level features are learned by the convolutional neural networks. In the 5-fold cross validation, the average values of Area Under the ROC curves and PRC curves for removed redundancy triplex-forming lncRNA dataset with threshold 0.8 are 0.9649 and 0.9996, and these two values for triplex DNA sites prediction are 0.8705 and 0.9671, respectively. Besides, we also briefly summarize the cis and trans targeting of triplexes lncRNAs. Conclusions: The TriplexFPP is able to predict the most likely triplex-forming lncRNAs from all the lncRNAs with computationally defined triplex forming capacities and the potential of a DNA site to become a triplex. It may provide insights to the exploration of lncRNA functions.
LAMP: disease classification derived from layered assessment on modules and pathways in the human gene network
Authors: Mi Zhilong , Guo Binghui , Yang Xiaobo , Yin Ziqiao , Zheng Zhiming
Published: October 2020

Background: Classification of diseases based on genetic information is of great significance as the basis for precision medicine, increasing the understanding of disease etiology and revolutionizing personalized medicine. Much effort has been directed at understanding disease associations by constructing disease networks, and classifying patient samples according to gene expression data. Integrating human gene networks overcomes limited coverage of genes. Incorporating pathway information into disease classification procedure addresses the challenge of cellular heterogeneity across patients.
Results: In this work, we propose a disease classification model LAMP, which concentrates on the layered assessment on modules and pathways. Directed human gene interactions are the foundation of constructing the human gene network, where the significant roles of disease and pathway genes are recognized. The fast unfolding algorithm identifies 11 modules in the largest connected component. Then layered networks are introduced to distinguish positions of genes in propagating information from sources to targets. After gene screening, hierarchical clustering and refined process, 1726 diseases from KEGG are classified into 18 categories. Also, it is expounded that diseases with overlapping genes may not belong to the same category in LAMP. Within each category, entropy is applied to measure the compositional complexity, and to evaluate the prospects for combination diagnosis and gene-targeted therapy for diseases.
Conclusions: In this work, by collecting data from BioGRID and KEGG, we develop a disease classification model LAMP, to support people to view diseases from the perspective of commonalities in etiology and pathology. Comprehensive research on existing diseases can help meet the challenges of unknown diseases. The results provide suggestions for combination diagnosis and gene-targeted therapy, which motivates clinicians and researchers to reposition the understanding of diseases and explore diagnosis and therapy strategies.
Value of Biopsy in a Cohort of Children with High-Titer Celiac Serologies: Observation of Dynamic Policy Differences between Europe and North America
Authors: Badizadegan Kamran , Vanlandingham David M. , Hampton Wesley , Thompson Kimberly M.
Published: October 2020

Background : Healthcare systems implement change at different rates because of differences in incentives, organizational processes, key influencers, and management styles. A comparable set of forces may play out at the national and international levels as demonstrated in significant differences in the diagnostic management of pediatric Celiac Disease (CD) between European and North American practitioners. Methods : We use retrospective clinical cohorts of 27,868 serum tissue transglutaminase (tTG) immunoglobulin A levels and 7,907 upper gastrointestinal endoscopy pathology reports to create a dataset of 793 pathology reports with matching tTG results between July 1 of 2014 and July 1 of 2018. We use this dataset to characterize histopathological findings in the duodenum, stomach and esophagus of patients as a function of serum tTG levels. In addition, we use the dataset to estimate the local and national cost of endoscopies performed in patients with serum tTG levels greater than 10 times the upper limit of normal. Results : Using evidence from a US tertiary care center, we show that in the cohort of pediatric patients with high pre-test probability of CD as determined by serum tTG levels, biopsy provides no additional diagnostic value for CD, and that it counter-intuitively introduces diagnostic uncertainty in a number of patients. We estimate that using the European diagnostic algorithms could avoid between 4,891 and 7,738 pediatric endoscopies per year in the US for evaluation of CD. Conclusions : This study considers the North American and European management guidelines for the diagnosis of pediatric CD and highlights the slow adoption in North America of evidence-based algorithms developed and applied in Europe for triage of endoscopy and biopsy. We suggest that system dynamics influences that help maintain the status quo in North America include a variety of social and economic factors in addition to medical evidence. This work contributes to the growing body of evidence that the dynamics that largely favor maintaining status quo management policies in a variety of systems extend to clinical medicine and potentially influence clinical decisions at the level of individual patients and the population.
Reproductive fluids, used for the in vitro production of pig embryos, result in healthy offspring and avoid aberrant placental expression of PEG3 and LUM.
Authors: Paris-Oller Evelynne , Navarro-Serna Sergio , Soriano-Úbeda Cristina , Lopes Jordana Sena , Matas Carmen , Ruiz Salvador , Latorre Rafael , López-Albors Octavio , Romar Raquel , Cánovas Sebastián , Coy Pilar
Published: October 2020

Background: In vitro embryo production (IVP) and embryo transfer (ET) are two very common assisted reproductive technologies (ART) in human and cattle. However, in pig, the combination of either procedures, or even their use separately, is still considered suboptimal due to the low efficiency of IVP plus the difficulty of performing ET in the long and contorted uterus of the sow. In addition, the potential impact of these two ART on the health of the offspring is unknown. We investigated here if the use of a modified IVP system, with natural reproductive fluids (RF) as supplements to the culture media, combined with a minimally invasive surgery to perform ET, affects the output of the own IVP system as well as the reproductive performance of the mother and placental molecular traits.Results: The blastocyst rates obtained by both in vitro systems, conventional (C-IVP) and modified (RF-IVP), were similar. Pregnancy and farrowing rates were also similar. However, when compared to in vivo control (artificial insemination, AI), litter sizes of both IVP groups were lower, while placental efficiency was higher in AI than in RF-IVP. Gene expression studies revealed aberrant expression levels for PEG3 and LUM in placental tissue for C-IVP group when compared to AI, but not for RF-IVP group.Conclusions: The use of reproductive fluids as additives for the culture media in pig IVP does not improve reproductive performance of recipient mothers but could mitigate the impact of artificial procedures in the offspring.
First report on molecular basis of potato leaf roll virus (PLRV) aggravation by combined effect of tuber and prevailing aphid
Authors: Kumar Ravi Ranjan , Ansar Mohammad , Rajani Kumari , Kumar Jitesh , Ranjan Tushar
Published: October 2020

Objective: The Potato Leaf Roll Virus (PLRV) is one of the most devastating virus causing severe yield losses worldwide in potato. The comprehensive observations were made to study the PLRV infestation in major potato growing areas of Bihar (India) and further detailed molecular basis of PLRV aggravation was established. Results: Although aphids population were found comparatively lower with maximum symptomatic plants, our molecular data further confirms the presence of PLRV in all possible symptomatic tissues such as tubers, shoots and leaves. For the first time, we have proposed molecular basis of aggravation of PLRV, where tuber acts as a reservoir during off-season and further transmitted by aphids.
Factors impacting the implementation of a psychoeducation intervention within the Mental Health System: a multisite study using the Consolidation Framework for Implementation Research
Authors: Higgins Agnes , Murphy Rebecca , Downes Carmel , Barry Jennifer , Monahan Mark , Hevey David , Kroll Thilo , Doyle Louise , Gibbons Patrick
Published: October 2020

Background Despite a strong evidence base and policy recommendation supporting the implementation of psychoeducation interventions within the mental health system, equitable access for many service users and family members has not been achieved. To enhance translation, developing an evidence-base around the factors that influence implementation of interventions is critical. Methods The aim of the study was to explore the factors influencing implementation of a group cofacilitated recovery focused psychoeducation intervention. The study design was explorative qualitative descriptive, involving the collection of data through individual and focus group interviews with key stakeholders (n=75) involved with the implementation within 14 mental health sites in the Republic of Ireland. The Consolidation Framework for Implementation Research (CFIR) was used as a conceptual framework to guide data collection and analysis. Results Key enablers and barriers were identified across all CFIR domains of the framework with some factors (depending on context) being both an enabler and a barrier. National policy; structural stability with national systems; leadership at all levels; peer payment system; local champions and support from multidisciplinary team members; evidence strength and quality of the programme design; availability of resources; referral pathways; knowledge, beliefs and self-efficacy of facilitators, as well as local culture influenced implementation. While some were specific to the programme, many barriers reflected systemic and structural challenges within health services more generally. Conclusion: Findings from this study provide an enhanced understanding of the different layers of determinants to implementation of an intervention. Overcoming challenges will involve positive and ongoing engagement and collaboration across the full range of stakeholders that are active within each domain, including policy and operational levels. The quality of leadership at each domain level is of crucial importance to successful implementation.
The circular RNA circZFR phosphorylates Rb promoting cervical cancer progression by regulating the SSBP1/CDK2/cyclin E1 complex
Authors: Zhou Mingyi , Yang Zhuo , Wang Danbo , Chen Peng , Zhang Yong
Published: October 2020

Background: As a novel type of non-coding RNA, circular RNAs (circRNAs) play a critical role in the initiation and development of various diseases, including cancer. However, the exact function of circRNAs in human cervical cancer remains largely unknown.Methods: We identified the circRNA signature of upregulated circRNAs between cervical cancer and paired adjacent normal tissues. Using two different cohorts and GEO database, a total of six upregulated circRNAs were identified with a fold change >2, and P <0.05. Among these six circRNAs, hsa_circ_0072088 (circZFR) was the only exonic circRNA significantly overexpressed in cervical cancer. Functional experiments were performed to investigate the biological function of circZFR. CircRNA pull-down, circRNA immunoprecipitation (circRIP) and Co-immunoprecipitation (Co-IP) assays were executed to investigate the molecular mechanism underlying the function of circZFR.Results: Functionally, circZFR knockdown represses the proliferation, invasion, and tumor growth. Furthermore, circRNA pull-down experiments combined with mass spectrometry unveil the interactions of circZFR with Single-Stranded DNA Binding Protein 1 (SSBP1). Mechanistically, circZFR bound with SSBP1, thereby promoting the assembly of CDK2/cyclin E1 complexes. The activation of CDK2/cyclin E1 complexes induced p-Rb phosphorylation, thus releasing activated E2F1 leading to cell cycle progression and cell proliferation.Conclusion: Our findings provide the first evidence that circZFR is a novel onco-circRNA and might be a potential biomarker and therapeutic target for cervical cancer patients.
Genome-wide identification of microRNAs associated with the somatic embryogenesis in Eucalyptus
Authors: Qin Zihai , Li Junji , Zhang Ye , Xiao Yufei , Zhang Xiaoning , Liu Hailong , Chen Bowen
Published: October 2020

Background: MicroRNAs (miRNAs) are a class of small noncoding RNAs with 18-24 nucleotides in length and function in many biological processes in plant. Although Eucalyptus trees are widely planted across the world, our understanding of the miRNA regulation in the somatic embryogenesis of Eucalyptus is still poor. Here we reported for the first time the miRNA profiles of differentiated and dedifferentiated tissues of two Eucalyptus cultivars and identified miRNAs involved in the somatic embryogenesis of Eucalyptus.Results: Stem and tissue-culture induced callus were obtained from the subculture seedlings of E. camaldulensis and E. grandis x urophylla, and were used as differentiated and dedifferentiated samples, respectively. We generated 346.4 million reads for 12 samples (n=3) and identified 888 miRNA precursors (197 known and 691 novel) which can produce 1,067 mature miRNAs. These miRNAs were mainly distributed in chromosomes Chr03, Chr05 and Chr08, and can produce 46 miRNA clusters. In these samples we detected 998 miRNAs with TPM (transcripts per million reads) > 5 and found that highly expressed miRNAs varied across samples. We identified 327 and 343 differentially expressed miRNAs in the dedifferentiation process of E. camaldulensis and E. grandis x urophylla, respectively. Dysregulated miRNAs shared by the two cultivars might be involved in the development of embryonic callus of Eucalyptus, such as MIR156, MIR159, MIR160, MIR164, MIR166, MIR169, MIR171, MIR399 and MIR482. We also identified 81 up-regulated (e.g., miR159c-3p, miR167a-5p, miR397a-3p, miR397c-5p, miR397d-3p, miR397d-5p, N-miR1-5p and N-miR5-5p) and 67 down-regulated (e.g., miR482b-3p, N-miR3-3p, miR156a-3p, N-miR40-3p and N-miR18-5p) miRNAs specific to E. camaldulensis. Target prediction and functional analysis showed they might be involved in longevity regulating and plant hormone signal transduction pathways. Then, the expression patterns of these miRNAs were confirmed by qRT-PCR. Conclusions: This is the first time to study the miRNAs profiles in the dedifferentiation process of Eucalyptus and it will provide a valuable resource for future studies. More importantly, our findings will improve our understanding of miRNA regulation and molecular mechanisms during the somatic embryogenesis of Eucalyptus, and the output of this study will benefit the Eucalyptus breeding program.
Genomic survey sequencing, development and characterization of single- and multi-locus genomic SSR markers of Elymus sibiricus L.
Authors: Xiong Yi , Lei Xiong , Bai Shiqie , Xiong Yanli , Liu Wenhui , Wu Wendan , Yu Qingqing , Dong Zhixiao , Yang Jian , Ma Xiao
Published: October 2020

Background: Siberian wildrye (Elymus sibiricus L.) attracts considerable interest for grassland establishment and pasture recovery in the Qinghai-Tibet Plateau (QTP) due to its excellence in strong stress tolerance, high nutritional value and ease to cultivate. However, the lack of genomic information of E. sibiricus hampers its genetics study and breeding process.Results: In this study, we performed a genome survey and developed a set of SSR markers for E. sibiricus based on Next-generation sequencing (NGS). We generated 469.17 Gb clean sequence which is 58.64× of the 6.86 Gb estimated genome size. We assembled a draft genome of 4.34 Gb which has 73.23% repetitive elements, a heterozygosity ratio of 0.01% and GC content of 45.68%. Based on the gnomic sequences we identified 67,833 SSR loci and from which four hundred were randomly selected to develop markers. Finally, 30 markers exhibited polymorphism between accessions and ten were identified as single-locus SSR. These newly developed markers along with previously reported 30 ones were applied to analyze genetic polymorphism among 27 wild E. sibiricus accessions. We found that single-locus SSRs are superior to multi-loci SSRs in effectiveness.Conclusions: This study provided insights into further whole genome sequencing of E. sibiricus in strategy selection. The novel developed SSR markers will facilitate genetics study and breeding for Elymus species.
Financial Inclusion and the Growth of Small Medium Enterprises in Uganda: Empirical Evidence from Selected Districts in Lango Sub Region
Authors: Eton Marus , Mwosi Fabian , Okello-Obura Constant , Turyehebwa Abanis , Uwonda Gilbert
Published: October 2020

The growth and failure of small and medium enterprises has been a topic of discussions world over amongst policy makers and researchers. This study was guided by the following objectives: To examine the contributions of Small Medium Enterprises (SMEs), to determine the challenges affecting Small Medium Enterprises, to examine how financial inclusiveness supports the growth of Small medium enterprises and to establish the relationship between financial inclusion and Small Medium Enterprises. The study used a cross sectional research design. Descriptive design was used and supplemented by inferential statistics. Correlation and regression analysis were adopted. The study revealed that financial inclusion is significant in supporting SMEs growth. The study also revealed that cost of acquiring and servicing financial services are high, there is also difficulty in using some of the financial services, and the way financial providers treat financial users, some lacked some degree of respect and dignity. The study recommends that financial providers should continue sensitizing the public on the available financial services beyond credit services, which are common and known. Digital financial service providers should encourage their clientele to use digitalized financial services which are cheap, secure and risk averse. Cost of capital should also be reduced to encourage borrowing while SMEs should innovatively produce goods that can be competitive at both domestic and international markets.
Sleep quality and athletic performance according to chronotype
Authors: Lim Seung-Taek , Kim Do-Yoon , Kwon Hyeong-Tae , Lee Eunjae
Published: October 2020

Background: When studying the quality of sleep in relation to athletic performance, the athlete's chronotype and habitual time consider important factors. We aim to investigate the sleep quality and athletes’ performance according to chronotype in elite athletes. Methods: Three hundred forty elite athletes (males = 261, females = 79) were recruited for the present study. All participants were screening for chronotype by the Korean versions of the Morningness - Eveningness Questionnaire (MEQ-K). The Pittsburgh Sleep Quality Index (PSQI) and Wingate Anaerobic Test (WAnT) were measurement after screening.Results: PSQI global score, PSQI sleep quality, PSQI sleep onset latency, PSQI sleep disturbance, and PSQI daytime dysfunction were significant differences among the groups. WAnT mean power (W), mean power (W/kg), peak power (W), and peak power (W/kg) were significant differences among the groups. A negative correlation coefficient was found between PSQI score and WAnT mean power (W), mean power (W/kg), peak power (W), and peak power (W/kg).Conclusions: This study indicates that related poor sleep quality and late-type chronotype may reduce the athletes’ performance in elite athletes. In addition, the sleep quality is much better in the early-type chronotype than in the late-type chronotype. Moreover, it also the athletic performance was better in the early-type chronotype than in the late-type chronotype.
Psychometric validation of the Laval Developmental Benchmarks Scale for Family Medicine
Authors: Renaud Jean-Sebastien , Lacasse Miriam , Côté Luc , Théorêt Johanne , Rheault Christian , Simard Caroline
Published: October 2020

Background: With the implementation of competency-based education in family medicine, there is a need for summative end-of-rotation assessments that are criterion-referenced rather than normative. Laval University’s family residency program therefore developed the Laval Developmental Benchmarks Scale for Family Medicine (DBS-FM), based on competency milestones. This psychometric validation study investigates its internal structure and its relation to another variable, two sources of validity evidence. Methods: We used assessment data from a cohort of residents (n=1 432 assessments) and the Rasch Rating Scale Model to investigate its reliability, dimensionality, rating scale functioning, targeting of items to residents’ competency levels, biases (differential item functioning), items hierarchy (adequacy of milestones ordering), and score responsiveness. Convergent validity was estimated by its correlation with the clinical rotation decision (pass, in difficulty/fail). Results: The DBS-FM can be considered as a unidimensional scale with good reliability for non-extreme scores (.83). The correlation between expected and empirical items hierarchies was of .78, p < .0001.Year 2 residents achieved higher scores than year 1 residents. It was associated with the clinical rotation decision. ﻿Conclusion: Advancing its validation, this study found that the DBS-FM has a sound internal structure and demonstrates convergent validity.
Early detection of non-invasive ventilation failure among acute respiratory failure patients in the Emergency Department
Authors: liengswangwong Wijittra , Yuksen Chaiyaporn Mahidol , Thepkong Tipanun , Nakasint Pornita , Jenpanitpong Chetsadakon
Published: October 2020

Background Non-invasive mechanical ventilation (NIV) has become an alternative to an invasive artificial airway for the management of acute respiratory failure (ARF). NIV failure causes delayed intubation, which eventually has been associated with increased morbidity and mortality. This study aimed to develop the clinical scoring system of NIV failure in ARF patients. Methods This study was a diagnostic, retrospectively cross-sectional, and exploratory model at the Emergency Medicine Department in Ramathibodi Hospital between February 2017 and December 2017. We included all of the acute respiratory failure patients aged >18 years and received non-invasive ventilation (NIV). Clinical factors associated with NIV failure were recorded. The predictive model and prediction score for NIV failure were developed by multivariable logistic regression analysis.Result A total of 329 acute respiratory failure patients have received NIV success (N = 237) and failure (N = 92). This study showed that NIV failure was associated with heart rate > 110 bpm, systolic BP < 110 mmHg, SpO2 < 90 %, arterial pH < 7.30 and serum lactate. The clinical scores were classified into three groups: low, moderate, and high.Conclusion We suggested that the novel clinical scoring of the NIV failure in this study may use as a good predictor for NIV failure in the emergency room.
The Immediate Effect of COVID-19 Pandemic on Children and Adolescents with Obsessive Compulsive Disorder
Authors: Nissen Judith Becker , Højgaard David , Thomsen Per Hove
Published: October 2020

Background Obsessive compulsive disorder (OCD) is a distressing psychiatric disorder. Traumas may trigger or aggravate OCD symptoms. COVID-19 pandemic has coursed a global crisis and has been associated with onset of psychiatric disorders in adults. Little is known about children/adolescents with OCD. The present study aimed to examine how children/adolescents with OCD react towards COVID-19 crisis. Methods A questionnaire was distributed to two separate groups of children/adolescents. One group was a clinical group newly diagnosed at a specialized OCD clinic. All the children/adolescents had a current close contact to a therapist or doctor. The other group was a survey group identified through the Danish OCD Association. Most of these children/adolescents were diagnosed years ago, and their primary treatment was completed. For the clinical group, data from patient files was available. Results In both groups, but most pronounced in the survey group, participants experienced a worsening of their OCD, anxiety, and depressive symptoms. The aggravation of OCD correlated with the worsening of anxiety, depressive symptoms, and the extent of avoidance behavior. For both groups, OCD aggressive symptoms predicted a significant worsening. Poor baseline insight showed a trend to predict a symptom worsening. The worsening was most pronounced in children with early age of onset and a family history of attention deficit hyperactivity disorder. Conclusions To our knowledge, this is one of the first studies examining the effect of COVID-19 in children/adolescents with OCD. The effect was examined in two separate populations strengthening the findings. The study points towards an influence of the OCD phenotype, baseline insight suggesting a continued vulnerability, and a family history of psychiatric disorders. Trial registration The study is approved by the Danish Data Protection Agency (1-16-02-147-20) registered 1 st of April 2020. Oral and written information was given to parents and patients and written consent from patients over 15 years and parents were received.
Unveiling role of Sphingosine-1-phosphate receptor 2 as a brake of epithelial stem cell proliferation and a tumor suppressor in colorectal cancer
Authors: Petti Luciana , Rizzo Giulia , Rubbino Federica , Elangovan Sudharshan , Colombo Piergiuseppe , Silvia Restelli , Piontini Andrea , Arena Vincenzo , Carvello Michele , Romano Barbara , Cavalleri Tommaso , Anselmo Achille , Ungaro Federica , D’Alessio Silvia , Spinelli Antonino , Stifter Sanja , Grizzi Fabio , Sgambato Alessandro , Danese Silvio , Laghi Luigi , Malesci Alberto , VETRANO STEFANIA
Published: October 2020

Background. Sphingosine-1-phosphate receptor 2 (S1PR2) mediates pleiotropic functions encompassing cell proliferation, survival, and migration, which become collectively de-regulated in cancer. Information on whether S1PR2 participates in colorectal carcinogenesis/cancer is scanty, and we set out to fill the gap.Methods. We screened expression changes of S1PR2 in human CRC and matched normal mucosa specimens [N=76]. We compared CRC arising in inflammation-driven and genetically engineered models in wild-type (S1PR2+/+) and S1PR2 deficient (S1PR2-/-) mice. We reconstituted S1PR2 expression in RKO cells and assessed their growth in xenografts. Functionally, we mimicked the ablation of S1PR2 in normal mucosa by treating S1PR2+/+ organoids with JTE013 and characterized intestinal epithelial stem cells isolated from S1PR2-/-Lgr5-EGFP- mice.Results. S1PR2 expression was lost in 33% of CRC; in 55%, it was significantly decreased, only 12% retaining expression comparable to normal mucosa. Both colitis-induced and genetic Apc+/min mouse models of CRC showed a higher incidence in size and number of carcinomas and/or high-grade adenomas, with increased cell proliferation in S1PR2-/- mice compared to S1PR2+/+ controls. Loss of S1PR2 impaired mucosal regeneration, ultimately promoting the expansion of intestinal stem cells. Whereas its overexpression attenuated cell cycle progression, it reduced the phosphorylation of AKT and augmented the levels of PTEN.Conclusions. In normal colonic crypts, S1PR2 gains expression along with intestinal epithelial cells differentiation, but not in intestinal stem cells, and contrasts intestinal tumorigenesis by promoting epithelial differentiation, preventing the expansion of stem cells and braking their malignant transformation. Targeting of S1PR2 may be of therapeutic benefit for CRC expressing high Lgr5.
Individual-based dengue virus surveillance in Aedes aegypti mosquitoes collected concurrently with suspected patients in Tarlac City, Philippines
Authors: Balingit Jean Claude , Carvajal Thaddeus M. , Saito-Obata Mariko , Gamboa Maribet , Nicolasora Amalea Dulcene , Sy Ava Kristy , Oshitani Hitoshi , Watanabe Kozo
Published: October 2020

Background: Vector control measures are critical in the prevention and reduction of dengue virus (DENV) transmission. In this context, effective vector control is reliant not only on knowledge of mosquito abundance, but also on the timely and accurate detection of mosquito infection. Mosquito-based virus surveillance programs commonly rely on pool-based mosquito testing, but whether individual-based mosquito testing could represent a feasible alternative is not largely studied. Applying an individual-based mosquito testing approach, we conducted a one-month DENV surveillance of adult Aedes aegypti mosquitoes around households of suspected dengue patients during the 2015 dengue peak season in Tarlac City, Philippines to more accurately assess the mosquito infection rate, and to identify the DENV serotypes and genotypes concurrently co-circulating in mosquitoes and patients. Methods: We performed a one-step multiplex real-time RT-PCR assay for the simultaneous detection and serotyping of DENV in patients and in individual female Ae. aegypti mosquito. Additionally, we performed sequencing and phylogenetic analyses to further characterize the detected DENVs in mosquitoes and patients at the genotype level. Results: We collected a total of 583 adult Ae. aegypti mosquitoes, of which we tested 359 female mosquitoes individually for the presence of the DENV. Ten mosquitoes (2.8%) from amongst 359 female mosquitoes were confirmed to be positive for the presence of the DENV. We detected DENV-1, DENV-2, and DENV-4 in the field-collected mosquitoes, which were consistent with the serotypes concurrently infecting patients. Sequencing and phylogenetic analyses of the detected DENVs based on the partial envelope (E) gene revealed three genotypes concurrently present in the sampled mosquitoes and patients during the study period, namely: DENV-1 genotype IV, DENV-2 Cosmopolitan genotype and DENV-4 genotype II. Conclusions: In this study, we demonstrate the utility of a one-step multiplex real-time RT-PCR assay in individual-based DENV surveillance of mosquitoes. Our findings reinforce the importance of detecting and monitoring virus activity in local mosquito populations, which is critical for dengue prevention and control activities.