bluuebunny/crossref_metadata_2025 huggingface dataset:
Experiential learning for children's dental anxiety: a cluster randomized trial
Authors: Zhu Minmin , Yu Hongbing , Xie Bo , Li Hongwen , He Qian , Li Huimin , Su Jing , Li Xueqi
Published: June 2020

Background: Dental anxiety (DA) has an impact on the quality of dental treatment and may have long-lasting implications for children. A recent study introducing experiential learning (EL) into children’s oral health promotion resulted in better oral hygiene. The purpose of the study is to evaluate whether EL can reduce children's DA. Methods: In September 2018, we recruited 988 children aged 7-8 years from 24 classes to participate in a cluster-randomized trial. Classes were randomly assigned to EL (in which children received a lively presentation on oral health and participated in a role play in a simulated dental clinic in the classroom) or the Tell-Show-Do (TSD) group (in which children received a conventional TSD behavior management). The primary outcome was the prevalence of DA after the procedure of pit and fissure sealant (PFS), assessed by a modified children's fear survey schedule-dental subscale. Secondary outcomes were changes in blood pressures (BP) and pulse rates (PR) before and after the PFS procedure. The intervention effects were estimated by means of mixed effect models, which included covariates of gender and school (and baseline value for BP and PR only), and a random cluster effect.Results: In 396 children of the EL group who received the PFS treatment, the prevalence of DA (score ≥ 38) was 18.5%, compared with 24.3% in 391 children of the TSD group (OR=0.65; 95% confidence interval, 0.46-0.93; P=0.019). The increases in BP and PR after the PFS were also significantly less in the EL group. Conclusions: School-based experiential learning intervention before a dental visit is feasible and effective in lowering children’s dental anxiety during PFS.Trial registration: The trial was registered in Chinese Clinical Trial Registry on 5 January 2020 (No.: ChiCTR2000028878, retrospectively registered), http://www.chictr.org.cn/edit.aspx?pid=47970&htm=4.
Contextual Effects of Social Integration and Disintegration on Health Status: Evidence from South Korea
Authors: Jo Eun-Bi , Kwon Rang Hee , Jung Minsoo
Published: June 2020

Background : Many studies have shown that various social integration variables represented by social capital are beneficial to communities, including collective health. However, the rapid decline in fertility rates and the breakup of familyism in developed countries require a new approach to social disintegration, but the literature is insufficient. Here, we explored the contextual effects of social integration and social disintegration on the health of individuals.

Methods : The research data consist of merged datasets of 6909 respondents who were quota-sampled by approximately 30 people from 229 local governments in Korea. The individual-level independent variable is a social integration measure consisting of 26 questions in four areas. The community-level independent variables are five integral and aggregate variables extracted from 81 indicators. The dependent variable is self-rated health status. Potential confounders are gender, age, annual income, educational attainment, district type, and the number of beds in medical institutions per 1,000 people.

Results : The results showed that at the individual level, the higher the inclusive attitude of in- and out-of-networks, after adjusting for potential confounders, the less likely the respondent belongs to the unhealthy group (p <0.001). At the community level, the higher the proportion of single-person households in a community after adjusting for potential confounders, the less likely the respondent belongs to the unhealthy group (p <0.05). The effect size was 0.22.

Conclusion : Thus far, social integration has been preferred, with the positive aspects of social capital being emphasized. However, this study shows that in some cases, social disintegration can instead positively influence an individual's health. Therefore, further studies of the various conditions of social context effects on health are necessary.
Cyclin H predicts a poor prognosis and promotes the proliferation in ovarian cancer
Authors: Peng Chen , Yang Yansong , Ji Li , Yang Panpan , Yang Xiaoqing , Zhang Yuquan
Published: June 2020

Background: Cell cycle dysregulation plays a key role in the pathogenesis of malignant tumor. As a part of CDK-activating kinase (CAK) trimeric complex, Cyclin H is necessary for the regulation of the cell cycle and proliferation. The objective of this investigation was to characterize the clinical significance and biological functions of cyclin H in ovarian cancer.Methods: Immunohistochemical staining was performed on 60 cases of ovarian cancer and the correlation between cyclin H expression and clinical characteristics was analyzed. The function of cyclin H in ovarian cancers was further explored using HO8910 cells and subcutaneous xenograft model of nude mice. Results: Cyclin H was slightly expressed in grade 1 ovarian cancer and highly expressed in high grade 2 and grade 3 tissues. The result of spearman rank correlation analysis showed that the expression of cyclin H positively correlated with tumor grade, the FIGO stage, histologic grade and peritoneal metastasis of ovarian cancer. Cyclin H was positively correlates with Ki67 and p-CDK2 in ovarian cancer. In addition, we found the five-year survival rate of cyclin H low expressed patients was higher than that in the cyclin H high expressed patients. Furthermore, knockdown of cyclin H was then achieved using a shRNA in HO8910 ovarian cancer cell line. Silencing of cyclin H resulted in G1/S cell cycle arrest of ovarian cancer cells and suppressed the growth of ovarian cancer. The expression of Ki67 was decreased in cyclin H silenced ovarian cancer. Conclusions: These results suggest that high expression of cyclin H predicts a poor prognosis and promotes the growth of ovarian cancer via regulating cell cycle.
Non-active implantable device treating acid reflux with a new dynamic treatment approach: 1-year results
Authors: Bjelović Miloš , Harsányi László , Altorjay Áron , Kincses Zsolt , Forsell Peter
Published: June 2020

BACKGROUND RefluxStop™ is an implantable, non-active, single use device used in the laparoscopic treatment of GERD. RefluxStop™ aims to block the movement of the LES up into the thorax and keep the angle of His in its original, anatomically correct position. This new device restores normal anatomy, leaving the food passageway unaffected. METHODS In a prospective, single arm, multicentric clinical investigation analyzing safety and effectiveness of the RefluxStop™ device to treat GERD, 50 subjects with chronic GERD were operated using a standardized surgical technique between December 2016 and September 2017. They were followed up for one year (CE-mark investigation 6-months). Primary safety outcome was prevalence of serious adverse events related to the device, and primary effectiveness outcome reduction of GERD symptoms based on GERD-HRQL score. Secondary outcomes were prevalence of adverse events other than serious adverse events, reduction of total acid exposure time in 24-hour pH monitoring, and reduction in average daily PPI usage and subject satisfaction. RESULTS There were no serious adverse events related to the device. Average GERD-HRQL total score at 1 year improved 86% from baseline (p<0.001). 24-hour pH monitoring compared to baseline showed a mean reduction percentage of overall time with pH<4 from 16.35% to 0.80% at the 6-month visit (p<0.001), with 98% of subjects showing normal 24-hour pH. At 1 year: No new cases of dysphagia were recorded, present in 2 subjects, which existed already at baseline. Regular daily PPI usage occurred in all 50 subjects at baseline. At 1-year follow-up, only 1 subject took regular daily PPIs due to a too low placement of the device thereby prohibiting its function. None or minimal occasional episodes of regurgitation occurred in 97.8% of evaluable subjects. Gas bloating disappeared in 30 subjects and improved in 7 subjects.CONCLUSION The new principle of RefluxStop™ is safe and effective to treat GERD according to investigation results. At 1-year follow-up, both the GERD-HRQL score and 24-h pH monitoring results indicate success for the new treatment principle. In addition, with the dynamic treatment for acid reflux, which avoids compressing the food passageway, prevalence of dysphagia and gas bloating are significantly reduced.
Classification and morphology of middle mesial canals of mandibular first molars in a Southern Chinese subpopulation: a cone-beam computed tomographic study
Authors: Yang Yeqing , Chen Ming , Zeng Junkai , Wu Buling
Published: June 2020

Background: Cone-beam computed tomography (CBCT) was employed to study the morphology and curvature of middle mesial canals (MMCs) of mandibular first molars (MFMs).Methods: CBCT scanning was performed on MFMs of 1100 patients. Patients' images that met the inclusion criteria were divided into group A (<40 years old) and group B (≥40 years old) for further study. The images were used to study the incidence of MMCs at different ages, measure the curvature of MMCs in the mesiodistal and buccolingual directions using the Schneider method, and observe the anatomical morphology of the mesial root canal system.Results: In 875 patients, 1750 MFM images met the inclusion criteria. Among these cases, 158 MFMs contained an MMC, yielding an incidence rate of 9.03%. The incidence rate of MMCs was 11.22% in group A and 6.61% in group B, and this difference was statistically significant (P<0.05). The curvature in the mesiodistal direction was 29.39±8.53º in group A and 26.06±8.50º in group B, and this difference was also significant (P<0.05). The curved regions in groups A and B were often located in the middle 1/3 of canal. No significant difference in the distance between MMC orifices and mesiobuccal canal orifices or mesiolingual canal orifices was noted (P>0.05). The most common mesial root canal morphological type was type II (3-2) (53.80%). Conclusion: The incidence of MMCs in MFMs declined as age increased. The canal systems of MMCs were varied and complex, mainly exhibiting an obvious mesiodistal curve. CBCT is an outstanding method to help guide root canal therapy.
Transposable element abundance correlates with mode of transmission in microsporidian parasites
Authors: de Albuquerque Nathalia Rammé Medeiros , Ebert Dieter , Haag Karen Luisa
Published: June 2020

The extreme genome reduction and physiological simplicity of some microsporidia has been attributed to their intracellular, obligate parasitic lifestyle. Although not all microsporidian genomes are small (size range from about 2 to 50 MB), it is suggested that the size of their genomes has been streamlined by natural selection. We explore the hypothesis that vertical transmission in microsporidia produces population bottlenecks, and thus reduces the effectiveness of natural selection. Here we compare the transposable element (TE) content of 47 microsporidian genomes, and show that genome size is positively correlated with the amount of TEs, and that species that experience vertical transmission have larger genomes with higher proportion of TEs. Our findings are consistent with earlier studies inferring that nonadaptive processes play an important role in microsporidian evolution.
Electrochemical assessment of pigments-binding media interactions in oil paint deterioration: a case study on indigo and Prussian blue
Authors: Doménech-Carbó Antonio , Doménech-Carbó María Teresa , Osete-Cortina Laura , Donnici Margherita , Guasch-Ferré Nuria , Gasol-Fargas Rosa M. , Iglesias-Campos Manuel Ángel
Published: June 2020

The degradation of laboratory oil paint film specimens containing indigo and Prussian blue pigments and pictorial samples from the Sant Francesc de Paula painting exhibited in the Tomàs Balvey Arxiu Museum (Cardedeu (Catalonia), Spain) has been studied by voltammetry of immobilized particles. This technique, combined with light microscopy, scanning electron microscopy-energy dispersive X-ray analysis, nanoindentation-atomic force microscopy, attenuated total reflectance-Fourier-transform infrared spectroscopy and gas chromatography-mass spectroscopy techniques permits one to propose a dual scheme for the degradation of the pigments when naturally aged and submitted to accelerated UVA aging. Under conditions of moderate temperature, humidity and natural illumination, and low gradients of these parameters, Prussian blue acts as a radical scavenger moderating the production of reactive oxygen species produced in the oil binding medium by the action of ultraviolet radiation, resulting in the formation, in the solid state, of the solid-solution, {KFeIII[FeII(CN)6]}x{FeIII[FeIII(CN)6]}1–x, known as Berlin green, which then promotes the formation of indigo adducts with radicals. In the case of localized areas of the Sant Francesc de Paula paint, strong degradation occurs where Prussian blue acts as a promoter of the indigo oxidation to isatin, thus resulting in a considerable chromatic shift.
Prognostic significance of MYCN related genes in pediatric neuroblastoma: a study based on TARGET and GEO datasets
Authors: Wang Haiwei , Wang Xinrui , Xu Liangpu , Zhang Ji , Cao Hua
Published: June 2020

Background: Neuroblastoma patients with MYCN amplification are associated with poor prognosis. However, the prognostic relevance of MYCN associated genes in neuroblastoma is unclear. Methods: The expression profiles of MYCN associated genes were identified from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) datasets. Enriched transcription factors and signaling pathways were determined using gene set enrichment analysis (GSEA). Kaplan-Meier plotter was used to identify the prognostic relevance of MYCN associated genes. Multivariate cox regression and Spearman’s correlation were used to determine the correlation coefficients of MYCN associated genes.Results: In TARGET and GSE85047 datasets, neuroblastoma patients with MYCN amplification were associated with worse prognosis. Transcription factor MYC was positively associated with MYCN amplification in GSEA assay. We identified 13 MYC target genes which were increased in neuroblastoma patients with MYCN amplification in TARGET, GSE19274 and GSE85047 datasets. Moreover, six out of the 13 MYC target genes ARMC6, DCTPP1, EIF4G1, ELOVL6, FBL and PRMT1 were associated with adverse prognosis in TARGET and GSE85047 datasets. Transcription factor E2F1 was up-regulated by MYCN amplification and associated with the poor prognosis of neuroblastoma. Furthermore, RPS19 in ribosome signaling pathway was also associated with MYCN amplification and correlated with the poor prognosis of neuroblastoma. At last, we showed that most of MYCN target genes were correlated with each other. However, EIF4G1 was an independent prognostic marker. And the prognostic effects of the combination of MYCN amplification and EIF4G1 expression were more significant than MYCN or EIF4G1 alone.Conclusions: MYCN target genes ARMC6, DCTPP1, EIF4G1, ELOVL6, FBL, PRMT1, E2F1 and RPS19 had significant prognostic effects in pediatric neuroblastoma. And neuroblastoma patients without MYCN amplification and low EIF4G1 expression had best prognosis.
“Oil-soluble” Reversed Lipid Nanoparticles for Oral Insulin Delivery
Authors: Wang Tao , Shen Liao , Zhang Yadan , Li Haiyan , Wang Yongan , Quan Dongqin
Published: June 2020

Background: In this study, we aimed to design a novel oral insulin delivery system, named “oil-soluble” reversed lipid nanoparticles (ORLN), in which a hydrophilic insulin molecule is encapsulated by a phospholipid (PC) shell and dissolved in oil to prevent the enzymatic degradation of insulin. ORLN was characterized by transmission electron microscopy and dynamic light scattering. Results: In vitro enzymatic stability studies showed higher concentrations of insulin in cells incubated with ORLN-encapsulated insulin than in those incubated with free insulin solution in artificial intestinal fluid (pH 6.5). The protective effect of ORLN was attributed to its special release behavior and the formulation of the PC shell and oil barrier. Furthermore, an in vivo oral efficacy study confirmed that blood glucose levels were markedly decreased after ORLN administration in both healthy and diabetic mice. In vivo pharmacokinetic results showed that the bioavailability of ORLN-conjugated insulin was approximately 28.7% relative to that of the group subcutaneously administered with an aqueous solution of insulin, indicating enhanced oral absorption.Conclusions: In summary, the ORLN system developed here shows promise as a nanocarrier for improving the oral absorption of insulin.
Transcriptome analysis reveals underlying immune response mechanism of fungal disease in Gastrodia elata Bl. f. glauca S. Chow
Authors: Wang Yanhua , Gao Yugang , Zang Pu , Xu Yue
Published: June 2020

Background
Gastrodia elata Bl. f. glauca S. Chow is a rare medicinal plant. G. elata f. glauca is unavoidably infected by pathogens in their growth process, for they are usually grown in a semi-wild state. If it happens, that will seriously affect the yield and quality of their tubers. In previous work, we have successfully isolated and identified the pathogenic fungus from infected tubers in G. elata f. glauca. In this study, healthy and fungal diseased mature tubers of G. elata f. glauca from Changbai Mountain area were used as experimental materials.
Results
A total of 7540 differentially expressed Unigenes (DEGs) were identified (FDR < 0.01, log2FC > 2). Further analysis revealed that transcription factors (TFs) in plant hormone signal transduction pathway and plant pathogen interaction pathway, like WRKY22, GH3, TIFY/JAZ, ERF1, WRKY33, TGA, played vital role in fungal disease response. They mainly involved signal transduction, environmental adaptation, biosynthesis/metabolism of secondary metabolites. In addition, we found jasmonic acid/ethylene is the noteworthy signaling pathway in response to fungal disease in G. elata f. glauca.
Conclusions
The results reveal an underlying immune response mechanism of fungal disease in G. elata f. glauca and provide a novel insight into the breeding of disease resistant varieties of G. elata f. glauca.
Defining treatment strategy for uncomplicated appendicitis based on patient satisfaction feedback: A cross-sectional study
Authors: Tatsuta Kyota , Miyazaki Shinichiro , Ogiku Masahito , Harada Takashi , Yoshiro Nishiwaki
Published: June 2020

Background
Two surgical strategies are available for appendicitis: emergency laparoscopic appendectomy and interval laparoscopic appendectomy. However, timing of surgical intervention remains debatable. This study aimed to compare the surgical outcomes of emergency laparoscopic appendectomy (ELA) and interval laparoscopic appendectomy (ILA) and conduct a questionnaire survey to investigate the use of ELA and patient satisfaction with regard to treatment.
Methods
We included 162 patients who underwent laparoscopic appendectomy at our hospital. Outcomes were assessed by operation time, blood loss, postoperative fasting time, length of hospital stay, and complication rate. Patient satisfaction was measured by questionnaire addressing degree of satisfaction, pre-surgery anxiety, and length of hospital stay. Continuous variables were compared by Student’s t-test, and discrete variables, expressed as percentages, were analyzed via chi-squared test.
Results
Of 162 patients, 74 (46%) and 88 (54%) received emergency and ILA, respectively. No significant difference was observed in the operation time, blood loss, length of hospital stay, or complication rate. Among 66 patients who responded to the questionnaire (28 emergency, 38 interval), a significant difference was observed only in the degree of satisfaction regarding the timing of the surgical intervention (p = 0.04).
Conclusions
Surgical outcomes of emergency and interval appendectomy were equivalent; however, patient satisfaction favored emergency appendectomy, suggesting it is a preferable approach for the treatment of uncomplicated appendicitis.
Trial registration:
NA
Most colitis associated carcinomas lack expression of LGR5: implications for unique pathways of carcinogenesis compared to sporadic colorectal carcinoma
Authors: Iwaya Mai , Ota Hiroyoshi , Nakajima Tomoyuki , Uehara Takeshi , Riddell Robert , Conner James
Published: June 2020

BackgroundLeucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), a component of the Wnt receptor complex, is thought to lineage label gastric and intestinal stem cells. LGR5 expression is increased in colorectal carcinoma (CRC) compared to normal tissue. Colitis associated colorectal adenocarcinoma (CAC) often shows distinct morphologic and molecular phenotypes compared to sporadic cases. However, the expression profile of LGR5, and by extension the potential role of an intestinal stem cell phenotype, has not been well described in a series of human CAC. MethodRNA in situ hybridization (ISH) for LGR5 expression on 30 CACs (12 cases with conventional morphology and 18 cases with non-conventional type morphology) from 29 inflammatory bowel disease (IBD) patients was performed and compared the expression profile to a control group of 10 sporadic CRCs. ResultLGR5 was positive in 30% (9/30) of CAC cases and 90% (9/10) of sporadic CRCs (p=0.002). A large majority (89%) of LGR5 positive CACs were of the conventional histologic type, and conventional type CAC showed a significantly higher LGR5 score (median 3.0; interquartile range 1.75-3.25) than non-conventional type CAC (median 1.5; interquartile range 1.00-2.00) (p = 0.034). CAC with conventional morphology did have a lower level of LGR5 expression than sporadic CRC. Sporadic CRCs showed a significantly higher LGR5 level score than non-conventional type CACs (p <0.001). ConclusionThese findings suggest that the wider spectrum of tumor morphology in CAC may be associated with absence of a LGR5-expressing intestinal stem cell phenotype.
Analysis for interaction between interleukin-35 gene polymorphisms and risk factors on susceptibility to coronary heart disease in the Chinese Han population
Authors: LI Hu , LIU Ying-Xue , Huang Jin-Yan , Zhu Yu- Feng , Wang Kui
Published: June 2020

Objective
To explore the effect of single nucleotide polymorphisms (SNPs) of interleukin-35 (IL-35) gene and its relationship with environment on the risk of coronary heart disease (CHD).
Methods
Prior to the analysis, we performed hardy Weinberg equilibrium test on the control group. The relationship between the four SNPs of IL-35 gene and the risk of coronary heart disease was studied by multivariate logistic regression. The best interaction was identified with generalized multifactor dimensionality reduction (GMDR). Logistic regression was used for investigation on association between four SNPs and CHD risk.
Results
Logistic regression analysis showed that the C allele of rs428253 and the G allele of rs2243115 were independently correlated with increased risk of CHD, and adjusted ORs (95%CI) were 1.91 (1.28–2.64) and 1.80 (1.30–2.23), respectively. However, there was no significant association between CHD and rs4740 or rs568408. GMDR model, indicated the best model for CHD risk consisted of rs428253 and current smoking, which scored 10/10 for both the sign test and cross-validation consistency (P = 0.010). Therefore, this overall multi-dimensional model had the highest cross-validation consistency, regardless of how the data were divided. This provided an evidence of gene-environment interaction effects. We also found that current smokers with rs428253 - GC/ CC genotype have the highest CHD risk, compared to subjects with never smokers with rs428253 - GG genotype, OR (95%CI) = 3.04 (1.71–4.41), after adjustment for age, gender, hypertension, T2DM and alcohol consumption status.
Conclusions
In this study, the C allele of rs428253 and the G allele of rs2243115, and the interaction rs428253 and current smoking were correlated with increased risk of CHD.
Restless abdomen: a spectrum or a phenotype variant of restless legs syndrome?
Authors: Wang Xi-Xi , Zhu Xiao-Ying , Wang Zan , Dong Jian-Wei , Ondo William G. , Wu Yun-Cheng
Published: June 2020

Background
With the growing awareness of restless legs syndrome(RLS), sensory disorders similar to RLS initially confined to the arms, abdomen, and perineum are more and more being recognized. One of them is restless abdomen, which refers to a restless sensation in abdomen. Our study is designed to evaluate the clinical phenotype of restless abdomen and investigate its relationship with RLS.
Methods
We enrolled 10 patients with restless abdomen according to the RLS diagnostic criteria. Laboratory examinations were performed to exclude mimics and notable comorbidities.
Results
All 10 patients had RLS like symptoms in the abdomen and otherwise satisfied all other RLS diagnostic criteria, and responded to dopaminergic therapy.
Conclusions
Neurologists should be aware of the RLS-related restlessness that can occur in extra-leg anatomy in the absence of episodes of worsening or augmentation of restlessness.
The Effect of The Body Composition to Prognosis in Young Breast Cancer Patients
Authors: Beypinar Ismail , Kaya Furkan , Demir Hacer
Published: June 2020

Background In cancer patients, the effect of the body composition on prognosis is a new clinical area of interest. In patients with class 2 or 3 obesity (BMI > 35), survival found to be worse control groups in a pooled analysis. BMI category is not truly representing body composition and hard to use to determine the true muscle and fat quantity. Computed tomography (CT) is a frequent method to determine body composition precisely.Methods Axial CT images, including all abdominal muscles (psoas, erector spinae, quadratus lumborum) external and internal oblique and rectus abdominis) total skeletal muscle area (SMA), was calculated. Besides, axial CT images of the body fat subcutaneous adipose and visceral adipose tissue distribution (VAT, SAT) areas were calculated in cm2 using threshold values ​​of -30 to -190 for adipose tissue.Results Eighty-four women included in the study. Most of the patients were normal or over-weighted. Invasive ductal carcinoma was the dominant histological subtypes, with 94% of the study population. The count of the sarcopenic and non-sarcopenic patients was 11 and 68 respectively. Although the median OS cannot be reached at the end of the follow-up period for both sarcopenic and non-sarcopenic patients, the difference between groups statistically insignificant. The median OS was not reached for both groups, the difference between low and high VAT groups was statistically significant.Conclusion In this study, we demonstrate sarcopenia may be seen in patients with breast cancer under 40 years old, and it may not have a prognostic effect.
Exploration of the role of tumor mutation burden in clinical significance, immunotherapy response predictor and immune cell infiltration in colon cancer
Authors: Xu Zhengshui , Qu Chao , Guo Jing , Li Xiaopeng , Wu Yunhua , Wang Kai , Zheng Jianbao , Sun Xuejun , Yu Junhui
Published: June 2020

Backgroud:Tumor mutation burden has become a powerful bio-marker to predict prognosis and immunotherapy responsiveness to patients in various cancers, but the role of TMB in colon cancer is still unclear.Methods:The transcriptome profiling data of colon patients and the simple nucleotide variation data of colon cases were downloaded from the Cancer Genome Atlas (TCGA) database. The groups were divided into high TMB and low TMB group according to the median of TMB. Then we explored the relationship between immune checkpoints, immune cells and TMB, respectively. Results: ﻿Mutation profiles of 399 colon cancer samples were analyzed in TCGA database. The senior (age＞65) had a strong relationship with higher-TMB level(p=0.001). Low-TMB group correlated with advanced N stage (P＜0.001), M stage (P＜0.001), and pathologic stage(P＜0.001). High-TMB group had significantly higher mRNA level of PD-L1, TIGIT, HAVCR2, and LAG3 than low-TMB group, which indicated high-TMB referred to better immunotherapy responsiveness in colon cancer. And high-TMB level correlated with higher fractions of CD8T cells (p=0.021), higher CD4 memory T cells(p=0.039), follicular helper T cells (p=0.002)and M1 macrophages (p＜0.001), while the low-TMB groups correlated with higher regulator T cells (p=0.002). So high-TMB correlated with stronger immune cell infiltrationConclusions:The high TMB referred to better clinical pathologic features, better immunotherapy responsiveness and stronger immune cells infiltration in colon cancer. Hence TMB may be a very promising bio-marker to predict prognosis and immunotherapy responsiveness to patients in colon cancer.
Poor Physical Capacity in Bronchiectasis Patients Is Correlated with Poor Quality of Life
Authors: Mäntylä Jarkko , Mazur Witold , Törölä Tanja , Bergman Paula , Kauppi Paula
Published: June 2020

Background: Bronchiectasis (BE) is an increasing burden on healthcare systems, and there is an urgent need for improved treatments, better clinical care and for clinical and translational research on this condition. Reducing the number of exacerbations is one of the key goals in BE management. Patients who suffer from frequent exacerbations are likely to experience more exacerbations, which have negative effects on quality of life (QoL), healthcare utilisation and mortality. Thus, we aimed to investigate the risk factors associated with quality of life (QoL) in a cohort of Finnish non-cystic fibrosis BE patients.Methods: A cross-sectional study is part of the EMBARC. Recruitment occurred between August 2016 and March 2018 from three clinics in Helsinki University Central Hospital, Finland. The study included 95 adult patients (mean age was 69 (SD± 13) years). Seventy nine percent were women. A disease-specific quality of life-bronchiectasis (QoL-B) questionnaire was applied, and scores in the lowest quarter (24%) indicate poor QoL. The bronchiectasis severity index (BSI) and FACED score were used. The severity of dyspnoea was examined using the modified Medical Research Council (mMRC) dyspnoea scale. Results: Almost all (82%) presented with chronic sputum production and exacerbation, with a median rate of 1.7 (SD ±1.6). Exacerbations (OR 1.7), frequent exacerbations (OR 4.9, p < 0.01), high BSI score (OR 1.3, p < 0.01) and extensive disease (OR 3.7, p = 0.05) were predictive of poor QoL. Frequent exacerbations were associated with bronchial bacterial colonisation, low forced expiratory volume in one second (FEV1) and radiological disease severity. Based on the BSI, 34.1% of our cohort had severe disease, whereas 11.6% were classified as severe according to the FACED score. The mMRC dyspnoea score (r = -0.57) and BSI (r = -0.60) were negatively correlated with physical domain in QoL-B questionnaire. Conclusion: Frequent exacerbations, radiological disease severity and high BSI score were predictive of poor QoL. Reduced physical capacity was correlated with dyspnoea and severity of disease. Interventions to reduce bacterial colonisation and to maintain physical functioning should be used to minimize exacerbations and to improve QoL.Study registration: University of Helsinki, faculty of medicine; 148/16.08.2017; Registered 16 August 2017; https://researchportal.helsinki.fi/
Impact of short-read sequencing on the misassembly of a plant genome
Authors: Wang Peipei , Meng Fanrui , Moore Bethany M. , Shiu Shin-Han
Published: June 2020

Background
Availability of plant genome sequences has led to significant advances. However, with few exceptions, the great majority of existing genome assemblies are derived from short read sequencing technologies with highly uneven read coverages indicative of sequencing and assembly issues that could significantly impact any downstream analysis of plant genomes. In tomato for example, 0.6% (5.1 Mb) and 9.7% (79.6 Mb) of short-read based assembly had significantly higher and lower coverage compared to background, respectively.
Results
To understand what the causes may be for such uneven coverage, we first established machine learning models capable of predicting genomic regions with variable coverages and found that high coverage regions tend to have higher simple sequence repeat and tandem gene densities compared to background regions. To determine if the high coverage regions were misassembled, we examined a recently available tomato long-read based assembly and found that 27.8% (1.41 Mb) of high coverage regions were potentially misassembled of duplicate sequences, compared to 1.4% in background regions. In addition, using a predictive model that can distinguish correctly and incorrectly assembled high coverage regions, we found that misassembled, high coverage regions tend to be flanked by simple sequence repeats, pseudogenes, and transposon elements.
Conclusions
Our study provides insights on the causes of variable coverage regions and a quantitative assessment of factors contributing to plant genome misassembly when using short reads.
Strengthening Retina Eye Care Services in Nepal: Retina Eye Care of Nepal project
Authors: Shrestha Arjun , Shrestha Chunu , Karki Pratap , Gurung Hara Maya , Naito Takeshi
Published: June 2020

BackgroundRetinal diseases are very difficult to treat. So, early diagnoses and preventions are very important. But, few eye doctors can treat patients with retinal diseases in Nepal.PurposeTo strengthen retina eye care services in NepalMethodsRetina Eye Care of Nepal (RECON) project was implemented from May 2016 to February 2019 in Nepal. Four Master Eye Doctors (MED) received Training of Trainers (TOT) from Tokushima University, Japan. MEDs developed training materials for different cadres of ophthalmic human resources, enhanced retina eye care facilities, and conducted retina-screening camp in Nepal.ResultTwenty ophthalmologists, 16 optometrists, 48 ophthalmic assistants and 17 ophthalmic nurses, 76 physicians and 28 health workers were trained in retina care. Eight outreach retina camps were conducted.ConclusionThe project was a novel approach to strengthen retina services in Nepal. The aim of the project was accomplished with the ultimate benefits to the needy retina patients who otherwise were going to miss the retina services.
Genome-Wide Association Studies and Whole-Genome Prediction Reveal the Genetic Architecture of KRN in Maize
Authors: An Yixin , Chen Lin , Li Yongxiang , Li Chunhui , Shi Yunsu , Zhang Dengfeng , Li Yu , Wang Tianyu
Published: June 2020

Background: Kernel row number (KRN) is an important trait for the domestication and improvement of maize. To explore the genetic basis of KRN has great research significance and can provide the valuable information for molecular assisted selection.Results: In this study, one single-locus method (MLM) and six multi-locus methods (mrMLM, FASTmrMLM, FASTmrEMMA, pLARmEB, pKWmEB and ISIS EM-BLASSO) of genome-wide association studies (GWASs) were used to identify significant quantitative trait nucleotides (QTNs) for KRN in an association panel including 639 maize inbred lines that were genotyped by the MaizeSNP50 BeadChip. In three phenotyping environments and with best linear unbiased prediction (BLUP) values, seven GWAS methods revealed different numbers of KRN-associated QTNs, ranging from 11 to 177. Based on these results, seven important regions for KRN located on chromosomes 1, 2, 3, 5, 9, and 10 were identified by at least three methods and in at least two environments. Moreover, 49 genes from the seven regions were expressed in different maize tissues. Among the 49 genes, ARF29 (Zm00001d026540, encoding auxin response factor 29) and CKO4 (Zm00001d043293, encoding cytokinin oxidase protein) were significantly related to KRN based on expression analysis and candidate gene association mapping. Whole-genome prediction (WGP) for KRN was also performed, and we found that the KRN-associated tagSNPs achieved a high prediction accuracy. The best strategy was to integrate the total KRN-associated tagSNPs identified by all GWAS models.Conclusions: These results aid in our understanding of the genetic architecture of KRN and provide useful information for genomic selection for KRN in maize breeding.
Knowledge, Attitude And Practice Of Ethiopian Paediatricians On Childhood Eye Diseases
Authors: Regassa Tolosa Tufa , Mengesha Aemero Abateneh , Daba Kumale Tolesa
Published: June 2020

Background: Eye examination and vision assessment are vital for the detection of conditions that result in blindness. Childhood blindness has serious impact on development, education and future employment opportunities for the affected child. Pediatrician’s knowledge about eye disease is important in preventing blindness by early diagnosis, proper treatment and identifying conditions requiring referral to the ophthalmologist to preserve or restore vision. The aim of this study was to assess knowledge, attitude and practice of Ethiopian pediatricians’ on childhood eye diseases.Methods: A cross-sectional descriptive study was done on 79 pediatricians working in various hospitals and clinics in Ethiopia. Participants were determined using convenient sampling technique. Data was collected using both closed and opened ended semi-structured questionnaires. Their responses were entered into EpiData 3.1 and transferred to Statistical Package for the Social Sciences (SPSS) version 21.0 software for analysis.Results: The findings of the study showed that participants in this study had positive attitude (94.9%) towards childhood eye diseases, even though this was not reflected in actual knowledge and practice. Poor knowledge and low practice in the context of positive attitude may be due to various barriers like inadequate training during undergraduate, lack ophthalmology attachment during pediatric residency and unavailability of ophthalmic equipment.Conclusions: Participants’ attitude towards childhood eye disease was positive, but their knowledge of eye diseases made their practice poor.
FGL1 Regulates Acquired Resistance to Gefitinib by Inhibiting Apoptosis in Non-small Cell Lung Cancer
Authors: Sun Cuilan , Gao Weiwei , Liu Jiatao , Cheng Hao , Hao Jiqing
Published: June 2020

Background: This study investigated the role of fibrinogen-like protein 1 (FGL1) in regulating gefitinib resistance of PC9/GR non-small cell lung cancer (NSCLC). Methods: The effect of different concentrations of gefitinib on cell proliferation were evaluated using the CCK-8 assay. FGL1 expression in the normal human bronchial epithelial cell line Beas-2B, as well as four lung tumor cell lines, H1975, A549, PC9, and PC9/GR, was investigated by using western blotting and qRT-PCR. FGL1 was knocked down using small interfering RNA to evaluate the effects of FGL1 on PC9 and PC9/GR. The correlation between FGL1 expression and gefitinib resistance was determined in vitro via CCK-8 and colony formation assays, and flow cytometry and in vivo via flow cytometry and immunohistochemistry.7 Results: FGL1 expression was significantly upregulated in non-small cell lung cancer cells with EGFR mutation and higher in the gefitinib-resistant NSCLC cell line PC9/GR than in the gefitinib-sensitive NSCLC cell line PC9. Further, FGL1 expression in PC9 and PC9/GR cells increased in response to gefitinib treatment in a dose-dependent manner. Knockdown of FGL1 suppressed cell viability, reduced the gefitinib IC50 value, and enhanced apoptosis in PC9 and PC9/GR cells upon gefitinib treatment. Mouse xenograft experiments showed that FGL1 knockdown in PC9/GR tumor cells enhanced the inhibitory and apoptosis-inducing actions of gefitinib. The potential mechanism of gefitinib in inducing apoptosis of PC9/GR cells involves inhibition of PARP1 and caspase 3 expression via suppression of FGL1.Conclusions: FGL1 confers gefitinib resistance in the NSCLC cell line PC9/GR by regulating the PARP1/caspase 3 pathway. Hence, FGL1 is a potential therapeutic target to improve the treatment response of NSCLC patients with acquired resistance to gefitinib.
A preoperative nomogram predicts prognosis of patients with hepatocellular carcinoma after liver transplantation: A multicenter retrospective study
Authors: Huang Dabing , Shen Yinan , Zhang Wei , Guo Chengxiang , Bai Xueli , Liang Ting-Bo
Published: June 2020

Background
Although criteria for liver transplantation, such as the Milan criteria and Hangzhou experiences, have become popular, criteria to guide adjuvant therapy for patients with hepatocellular carcinoma after liver transplantation are lacking.
Methods
We collected data from all consecutive patients from 2012 to 2019 at three liver transplantation centers in China retrospectively. Univariate and multivariate analyses were used to analyze preoperative parameters, such as demographic and clinical data. Using data obtained in our center, calibration curves and the concordance Harrell’s C-indices were used to establish the final model. The validation cohort comprised the patients from the other centers.
Results
Data from 233 patients were used to construct the nomogram. The validation cohort comprised 36 patients. Independent predictors of overall survival (OS) were identified as HbeAg positive (P = 0.044), blood-type compatibility unmatched (P = 0.034), liver transplantation criteria (P = 0.003), and high MELD score (P = 0.037). For the validation cohort, to predict OS, the C-index of the nomogram was 0.874. Based on the model, patients could be assigned into low-risk (≥ 50%), intermediate-risk (30–50%), and high-risk (≤ 30%) groups to guide adjuvant therapy after surgery and to facilitate personalized management.
Conclusions
The OS in patients with hepatocellular carcinoma after liver transplantation could be accurately predicted using the developed nomogram.
The Effectiveness of Prolotherapy for Recalcitrant Medial Tibial Stress Syndrome: A Prospective Case Series
Authors: Padhiar Nat , Curtin Mark , Aweid Osama , Awied Bashaar , Morrissey Dylan , Chan Otto , Malliaras Peter , Crisp Tom
Published: June 2020

Background: Medial tibial stress syndrome (MTSS) is one of the most common lower leg injuries in sporting populations. It accounts for between 6%-16% of all running injuries, and up to 53% of lower leg injuries in military recruits. Various treatment modalities are available with varying degree of success. In recalcitrant cases, surgery is often the only option.Objective: To evaluate whether ultrasound-guided injection of 15% dextrose for treatment of recalcitrant Medial Tibial Stress Syndrome decreases pain and facilitates a return to desired activity levels for those who may otherwise be considering surgery or giving up sport.Design: Prospective case seriesSetting: Private specialist CentrePatients: Eighteen patients: fifteen male and three female; (mean age=31.2 years) with MTSS were referred from sports injury clinics across the UK, having failed all available conservative treatment.Intervention: An ultrasound-guided sub-periosteal injection of 15% dextrose was administered by the same clinician (NP) along the length of the symptomatic area. Typically, 1 mL of solution was injected per cm of symptomatic area. Main Outcome Measures: Pain was assessed using a 10-cm visual analogue scale (VAS) at baseline, short-term, medium-term (mean 18 weeks) and long-term (mean one year) follow-up. Symptom resolution and return to activity were measured using a Likert scale at medium and long-term follow-up. Results: Patients reported a significant (p<0.01) reduction in median VAS pain score at medium and long-term follow-up compared to baseline. Median improvement per patient was 4.5/10. Patients rated their condition as ‘much improved’ at medium-term follow-up and median return to sport score was ‘returned to desired but not pre-injury level’ at medium-term and long-term follow-up. No adverse events were reported.Conclusions: Ultrasound-guided 15% dextrose prolotherapy injection has a significant medium-term effect on pain in MTSS. This benefit may be maintained long-term. More robust trials are required to validate these findings.Clinical Relevance: Clinicians should consider the use of ultrasound-guided injection of 15% dextrose as a viable treatment option to reduce pain and aid return to activity for patients with recalcitrant Medial Tibial Stress Syndrome.
The First De Novo Transcriptome Assembly From the Gonads of a Scleractinian Coral Euphyllia Ancora: Molecular Mechanisms Underlying Scleractinian Gametogenesis
Authors: Chiu Yi-Ling , Shikina Shinya , Yoshioka Yuki , Shinzato Chuya , Chang Ching-Fong
Published: June 2020

Background: Sexual reproduction of scleractinians has captured the attention of researchers and the general public for decades. Although extensive ecological data has been acquired, underlying molecular and cellular mechanisms remain largely unknown. In this study, to better understand mechanisms underlying gametogenesis, we isolated ovaries and testes at different developmental phases from a gonochoric coral, Euphyllia ancora, and adopted a transcriptomic approach to reveal sex- and phase-specific gene expression profiles. In particular, we explored genes associated with oocyte development and maturation, spermiogenesis, sperm motility / capacitation, and fertilization.Results: 1.6 billion raw reads were obtained from 24 gonadal samples. De novo assembly of trimmed reads, and elimination of contigs derived from symbiotic algae (Symbiodiniaceae) and other organisms yielded a reference E. ancora gonadal transcriptome of 35,802 contigs. Differential gene expression analysis of 4 developmental phases of ovaries and testes identified 2,023 and 678 differentially expressed genes in oogenesis and spermatogenesis, respectively. In premature/mature ovaries, 631 genes were specifically upregulated, with 538 in mature testes. Upregulated genes included those involved in gametogenesis, gamete maturation, sperm motility / capacitation, and fertilization in other metazoans, including humans. Meanwhile, a large number of genes without homology to sequences in the SWISS-PROT database were also observed among upregulated genes in premature / mature ovaries and mature testes.Conclusions: Our findings show that scleractinian gametogenesis shares many molecular characteristics with that of other metazoans, but it also possesses unique characteristics developed during cnidarian and/or scleractinian evolution. To the best of our knowledge, this study is the first to create a gonadal transcriptome assembly from any scleractinian. This study and associated datasets provide a foundation for future studies regarding gametogenesis and differences between male and female colonies from molecular and cellular perspectives. Furthermore, our transcriptome assembly will be a useful reference for future development of sex-specific and/or stage-specific germ cell markers that can be used in coral aquaculture and ecological studies.