bluuebunny/crossref_metadata_2025 huggingface dataset:
Does ACL reconstruction have any influence in meniscal repair? Sports return, quality of life and failure rate. 2-12 years follow up.
Authors: Rodríguez-Roiz Juan Miguel , Sastre-Solsona Sergi , Aleu Andrés Combalia , Popescu Dragos , Burillo Jordi Montañana
Published: May 2020

Objective

few studies approach with long follow up meniscal repair at amateur level, specially studying variables as quality of life and failure rate. We study medium to long-term clinical results in patients at amateur sports level, that have required meniscal sutures at our centre, with or without ACL reconstruction. We evaluate the objective function of the knee, as well as the patients’ return to sports activities, quality of life and the rate of failed repair and study the possible reasons.
Methods

We design an observational retrospective study, assessed 92 patients that required a meniscal repair in our centre from april 2007 until april 2018, who regularly perform amateur sports activities (Tegner 4 to 7), minimum follow-up period of 2 years, divided into 2 groups: group 1 isolated meniscal suture (43 cases), group 2 associated to ACL reconstruction (49 cases). Every patient have this tests in 2019: Lysholm and Tegner (validated for spanish) before the injury and after the surgical procedure, motivation to return to sports activity (Likert scale with 3 items: low, regular or high), quality of life (through SF-12 test).
Results

high return to amateur sports rate (92%), which was even higher in the isolated reconstruction group in comparison to the group with associated ACL, at a minimun follow-up of 2 years. We have not found statistically significant differences between sports return and: age, gender, injured meniscus, chondral injuries, preoperative Tegner score, or motivation. No significant differences in physical or mental health fields between both groups. Meniscal repair failed in 12 patients (13%,)and they finally required a partial meniscectomy, as complications just one debridement for superficial infection of ACL donor zone. Higher rate of failure in isolated bucket-handle tear injuries (p < 0.0062). We have not found a statistically significant association between the other variables studied.
Conclusions

92% of sports return and low meniscal repair failure rate, even lower when is associated to ACL reconstruction.
An Internal Cross-Linked Polymeric Nanoparticle with Dual Sensitivity for Combination Therapy of Muscle-Invasive Bladder Cancer
Authors: Zhu Guanchen , Wang Kaikai , Qin Haixiang , Zhao Xiaozhi , Chen Wei , Xu Linfeng , Cao Wenming , Guo Hongqian
Published: May 2020

Chemotherapy is an emerging effective treatment for cancer. However, one of the reasons why chemotherapy has a limited therapeutic effect in bladder cancer is that higher levels of glutathione in invasive bladder cancer cells. We have fabricated nanoparticles that sensitive to high concentrations of glutathione and near-infrared laser irradiation, which increases the drug accumulation at the tumor site and combines chemotherapy with photothermal therapy to overcome the challenges of bladder cancer treatment.Methods: The DOX&IR780@PEG-PCL-SS NPs were prepared by co-precipitation method. We investigated the tumor targeting of NPs in vitro and in vivo. The orthotopic bladder cancer model in C57BL/6 mice was established for in vivo study and photothermal effect of NPs were demonstrated. Therapeutic efficacy of NPs for bladder cancer was evaluated.Results: The DOX&IR780@PEG-PCL-SS NPs we synthesized use internal cross-linking strategy to increase the stability of nanoparticles. Nanoparticles can be ingested by tumor cells in a short time. The DOX&IR780@PEG-PCL-SS NPs have dual sensitivity to high levels of glutathione in bladder cancer cells and near-infrared laser irradiation. Glutathione triggers chemical structural changes in nanoparticles and preliminarily releases drugs, Near-infrared laser irradiation can promote the complete release of the drug from the nanoparticles, producing a photothermal effect and further killing the tumor cells. Given the excellent tumor-targeting ability and negligible toxicity, DOX&IR780@PEG-PCL-SS NPs can greatly increase the concentration of drugs in tumor cells. The mice in the experimental group can be found to have a significant reduction in tumor volume. The DOX&IR780@PEG-PCL-SS NPs can be tracked by small animal imaging and have good imaging results, to facilitate our assessment during the experiment.Conclusion: A dual sensitivity to glutathione and near-infrared laser irradiation. Long-circulating nanoparticle was developed for delivering IR780 and DOX, which could achieve NIR laser-controlled drug release and imaging guidance for chemo-photothermal synergistic therapy of both primary bladder cancer and their metastases.
Metastasis-associated protein 2 (MTA2) promotes the metastasis of esophageal squamous cell carcinoma via EIF4E-Twist feedback loop
Authors: Dai Suli , Wei Sisi , Zhang Cong , Li Xiaoya , Liu Yueping , Ma Ming , Lv Huilai , Zhao Lianmei , Shan Baoen
Published: May 2020

Background

Metastasis-associated protein 2 (MTA2) is frequently amplified in many types of cancers. However, the role and underlying molecular mechanism of MTA2 in esophageal squamous cell carcinoma (ESCC)remain unknown.
Methods

The expression of MTA2 in ESCC tissues and cell lines was detected by RT-qPCR, western blotting and immunohistochemistry. MTS and colony formation were used to analyze proliferation of ESCC cells. Transwell and wound healing assay were utilized to analyze ESCC cells migration and invasion. Xenograft experiments were used to analyze tumor growth and metastasis in vivo. Immunofluorescence was applied to test the influence of MTA2 on epithelial-mesenchymal transition (EMT). Microarray was used to test the interaction between MTA2 and EIF4E.Co- Immunoprecipitation(Co-IP) and Chromatin Immunoprecipi- tation (ChIP) assay were utilized to detect the occupation of MTA2 and Twist in the promoter region of E-cadherin.
Results

MTA2 was upregulated in ESCC tissues and cell lines. The upregulation of MTA2 in ESCC was correlated with malignant characteristics and poor survival probability of patients with ESCC. Through in vitro and in vivo experiments, we demonstrated that MTA2 significantly promoted ESCC growth, metastasis and EMT progression. Mechanistically, MTA2 could interact with EIF4E, which positively regulated the expression of Twist, and subsequently promote the malignant progression of ESCC. Moreover, the result of ChIP revealed that MTA2 was recruited to the promoter of E-cadherin by Twist to repress the transcription of E-cadherin.
Conclusion

MTA2 plays an aggressive role in ESCC metastasis by a novel EIF4E-Twist positive feedback loop, which may provide a potential therapeutic target for the management of ESCC.
Homodimerized GLP-1R agonists produce better efficacy in hypoglycemic effect or/and pancreatic protection in T2D models
Authors: Zhang Xu-Dong , Luo Qun , Tan Hong-Mei , Zhou| Xiao-Ying , He Qi-Ding , Liu Hui , Tang Jing-Xuan , Dong Yu-Xia , Liu Tao , Zhai Fu-Min , Tang Song-Shan , Huang Xin-Yu
Published: May 2020

The authors have removed this preprint from Research Square.
Heterogeneity of antidiabetic treatment effect on the risk of major adverse cardiovascular events in type 2 diabetes: a systematic review and meta-analysis
Authors: D'Andrea Elvira , Kesselheim Aaron S. , Franklin Jessica M. , Jung Emily , Hey Spencer Phillips , Patorno Elisabetta
Published: May 2020

Background
We explored whether clinically relevant baseline characteristics of patients with type 2 diabetes can modify the effect of glucagon-like peptide-1 receptor agonists (GLP-1 RA) or sodium-glucose cotransporter-2 inhibitors (SGLT-2i) on the risk of major adverse cardiovascular events (MACE).
Methods
We investigated Medline and EMBASE through June 2019. We included randomized clinical trials reporting the effect of GLP-1 RA or SGLT-2i on MACE in subgroups of patients with type 2 diabetes, identified through key baseline factors: established cardiovascular disease; heart failure; chronic kidney disease; uncontrolled diabetes; duration of diabetes; hypertension; obesity; age; gender and race. Hazard ratios (HRs) and 95% confidence intervals (CIs) from trials were meta-analyzed using random-effects models.
Results
Nine trials enrolling 87,143 patients were included in the analyses. Subgroup meta-analyses showed a 14% risk reduction of MACE in patients with established cardiovascular disease [GLP1-RA: HR, 0.86 (95% CI, 0.79–0.94); SGLT-2i: 0.86 (0.80–0.93)], and no effect in at-risk patients without history of cardiovascular events [GLP1-RA: 0.95 (0.83–1.08); SGLT-2i: 1.00 (0.87–1.16)]. We observed a trend toward larger treatment benefits with SGLT-2i among patients with chronic kidney disease [0.82 (0.69–0.97)], and patients with uncontrolled diabetes for both GLP1-RA or SGLT-2i [GLP1-RA: 0.82 (0.71–0.95); SGLT-2i: 0.84 (0.75–0.95)]. Uncontrolled hypertension, obesity, gender, age and race did not appear to modify the effect of these drugs.
Conclusions
In this exploratory analysis, history of cardiovascular disease appeared to modify the treatment effect of SGLT2i or GLP1-RA on MACE. Chronic kidney disease and uncontrolled diabetes should be further investigated as potential effect modifiers.
Gis-based Gully Erosion Susceptibility Modelling, Adapting Bivariate Statistical Method and Ahp Approach in Gombe Town and Environs Northeast Nigeria
Authors: Igwe Ogbonnaya , Ugwuoke Ikechukwu John , Solomon Onwuka , Obinna Ozioko
Published: May 2020

Gully erosion is a major environmental problem in Gombe town, large area of land is becoming unsuitable for human settlement, hence the need for gully erosion susceptibility map of the study area.To generate gully inventory map, detailed field exercise was carried out, during this investigation one hundred gullies were identified and studied extensively within the study area of about 550 km2. In addition to the mapped gullies, Google EarthPro with high resolution imagery was used to locate the spatial extents of fifty (50) more gullies. Ten gully erosion predisposing factors were carefully selected considering the information obtained from literature, and multiple field survey of the study area, the factors include: elevation, slope angle, curvature, aspect, topographic wetness index (TWI),soil texture, geology, drainage buffer, road buffer and landuse.In this study, a GIS-based Frequency Ratio (FR) and Analytical Hierarchy process (AHP) models were employed to predict areas prone to gully erosion in Gombe town and environs.The result obtained from FR shows that drainage, soil texture and slope have highest correlation with gully occurrence, while AHP modelrevealed that drainage buffer, soil texture, geology have high correlation with the formation of gully. Gully erosion susceptibility maps (GESM) were produced and reclassified into very high, high, moderate and low zones.The overall accuracies of both models weretested by means of area under curve(AUC) values and gully density distribution. FR and AHP model have AUC values of 0.73 and 0.72 respectively, the outcome indicates that both models have high prediction accuracy. The gully erosion density distribution values revealed that gullies are concentrated in the very high susceptibility class and it decreases towards the low class, Therefore the GESM produced using these models in this study area is reliable and can be used for land management and future planning
Cross-Cultural Adaptation and Validation of the Exercise Adherence Rating Scale to Nepali language: A Methodological Study
Authors: Adhikari Shambhu Prasad , Dev Rubee , Shrestha Jayana N
Published: May 2020

Background The Exercise Adherence Rating Scale (EARS) is a commonly used outcome tool, which helps to identify the adherence rate of exercises and reasons for adherence and non-adherence. There is no evidence of availability of any measurement tools to assess exercise adherence in Nepalese context and cultural background. Therefore, we conducted a cross-cultural adaptation of the EARS in to Nepali language and investigated its reliability and validity.Methods Cross-cultural adaptation of the EARS was done based on Beaton guidelines. Psychometric properties were evaluated among 18 participants aged 18 years or older with pre-diabetes or confirmed diagnosis of any disease who were prescribed with home exercises by physiotherapists. Any disease that limited participants from doing exercise and individuals unwilling to participate were excluded. Reliability was evaluated through internal consistency, using the Cronbach’s alpha. Exploratory Factor Analysis (EFA) was performed to explore construct validity and confirm its unidimensionality. Receiver Operating Characteristic (ROC) curve was analyzed to identify cut-off score, sensitivity and specificity of the tool.Results The Cronbach’s alpha was 0.94 for EARS-adherence behavior. The EFA of 6-items adherence behavior revealed the presence of one factor with an eigenvalue exceeding one. The scree-plot suggested for extraction of only one factor with strong loading (75.84%). The Area Under the Curve was 0.91 with 95% confidence interval 0.77 to 1.00 at p = 0.004. The cutoff score was found 17.5 with 89% sensitivity and 78% specificity.Conclusions The EARS was cross-culturally adapted to Nepali language. The reliability and construct validity of the Nepali version of the EARS were acceptable to assess exercise adherence in Nepali-speaking individuals. This validated tool might facilitate the evaluation of exercise related interventions. Future studies could investigate other psychometric properties of the Nepali EARS.
Practice of Exclusive Breastfeeding in the Talangai Health District, Congo: A Cross-Sectional Analytical Study
Authors: WOROMOGO SYLVAIN HONORE , Elenga Marie Binelvie Onday , Moussa Félicité Emma Yagata , ANTAON Jesse St Saba , TEBEU PIERRE MARIE
Published: May 2020

Objectives The objective of the study is to assess mothers' knowledge, attitudes and practices of exclusive breastfeeding (EBF) in the aim of improving the prevalence of exclusive breastfeeding. Study design An analytical knowledge, Attitudes and Practice (KAP) study about EBF on mothers of children aged 0-6 months was conducted. Methods Using SCHWARTZ formula, 362 mothers were included. The practice of EBF was determined based on a 24-h recall. The main variables studied were the socio-demographic characteristics of the mothers, their knowledge, attitudes and practices on EBF based on WHO recommendations A logistic regression analysis was performed and the odds ratio were calculated with 95% confidence interval. Results The prevalence of EBF among infants 0–6 months old was 33.9%. Mothers' knowledge, attitudes and practices were unsatisfactory (78.4%), favourable (79.5%) and bad (67.2%) respectively. Factors associated with satisfactory knowledge were being a public official [OR: 3.18 (1.39-7.28)] and or multiparous, [OR: 2.25 (1.23-4.11)]. Mothers who had a satisfactory knowledge had a higher rating of having good practices on EBF. Conclusions Factors related to good knowledge among mothers are multiparity, age and being a civil servant. Promoters’EBF must target mothers in all sectors of activity and even in the community by sensitizing them on the subject.
The Influence of Between and Within-group Variance on Recurrent Miscarriage in Ghana
Authors: Chireh Batholomew , Essien Samuel Kwaku , Melese Kidest Getu
Published: May 2020

Background: Recurrent miscarriage is a spontaneous loss of two or more pregnancies. It is a major global reproductive public health problem and the least researched in Ghana. There is an urgent need to move from more individualized and genetic risk factors that may be culturally inappropriate to assess and explore the influence of socio-ecological or contextual factors on recurrent miscarriage in Ghana. This study explored the between and within-group variance of zonal, regional, cluster, and household as well as the influence of selected socio-demographic characteristics on recurrent miscarriage.Methods: We conducted a secondary analysis of the 2017 cross-sectional demographic health survey data (25,062 women) in their reproductive ages (15-49 years) in Ghana. Data were collected from zones (3), regions (10), clusters (900), and households (27000). A logistic regression: Mixed effect model was used. Random effects were used to estimate the between and within groups differences in recurrent miscarriage. The fixed effects of selected socio-demographic variables were also assessed.Results: We found that cluster differences in recurrent miscarriage risk were more prominent compared to zonal, regional, and household. There was higher variability in recurrent miscarriage among women in the same household, cluster, and region compared to those from different households in the same cluster or those from different clusters in the same region and household. In the fixed-effects model, the odds of recurrent miscarriage were 1.54 times (95% CI=1.16-2.03) higher among urban dwellers than rural dwellers. Increasing maternal age was significantly associated with recurrent miscarriage (p=0.0001). There was a direction association between educational level and recurrent miscarriage. Insignificant protective factors of partner support and access to first-trimester antenatal care visits were also found.Conclusion: Differences in recurrent miscarriage risk exist at the contextual level and should be the focus of public health prevention efforts. Our key finding highlights the need to contextualize and localize recurrent miscarriage risk reduction efforts if interventions to reduce recurrent miscarriage in women with a history of unexplained pregnancy loss are to be successful in Ghana.
The effects of exercise and low-calorie diets compared with low-calorie diets alone on health: a protocol for systematic reviews and meta-analyses of controlled clinical trials
Authors: Beigrezaei Sara , Yazdanpanah Zeinab , Soltani Sepideh , Rajaei Seiedeh Hamideh , Mohseni-Takalloo Sahar , Zohrabi Tayebeh , Kaviani Mojtaba , Forbes Scott C. , Baker Julien S. , Salehi-Abargouei Amin
Published: May 2020

Background: Exercise and weight loss diets are two independent non-pharmaceutical strategies known to improve several aspects of body composition and health. We plan to systematically review randomized controlled trials investigating weight loss diets alone compared to weight loss diets in conjunction with exercise on energy intake, body weight, body composition, cardiometabolic risk factors, sex hormones, and mental health. Methods and analysis: PubMed/MEDLINE, EMBASE, ISI (Web of sciences), Scopus, and Google Scholar will be searched to retrieve potential controlled clinical trials investigating the effects of exercise in conjunction with weight-loss diets compared with weight-loss diets alone on energy intake, body weight and composition (fat mass, fat-free mass), anthropometrics (waist circumference), cardiometabolic markers, sex hormones [testosterone, estradiol, and sex hormone binding globulin (SHBG)], liver and kidney enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), uric acid, blood urea nitrogen (BUN), and glomerular filtration rate (GFR), quality of life, and depression in adults will be included. The weighted mean difference (WMD) and its corresponding 95% confidence intervals (CIs) will be derived using the random effects model. Several subgroup analyses such as gender, age, BMI, exercise protocol, and diet used for weight loss will be conducted to explore possible sources of heterogeneity. Publication bias will be explored by inspecting funnel plots and by conducting asymmetry tests. Overall quality of the evidence will be assessed by using the NutriGrade scoring system, which is designed to judge the overall quality of meta-analyses of clinical trials conducted in the field of nutrition. Discussion: This proposed systematic review and meta-analysis aims to compare the effects of a low-calorie diet with low-calorie diet plus exercise on the risk factors for chronic diseases. We hope this systematic review and meta-analysis will provide valuable information regarding the values which exercise add to weight-loss diets. No primary data are going to be collected; therefore, ethical approval is not required. The resulting manuscripts will be disseminated in peer-reviewed journals and at international and local conferences. Systematic review registration: This protocol in being considered for registration in the International Prospective Register of Systematic Reviews (PROSPERO).
Biomechanical Comparison of Three Kinds of Minimally Invasive Internal Fixation in the Treatment of Pelvic Bilateral Anterior Ring Fractures
Authors: Zhao Yong , Ma Yupeng , Zou Dexin , Sun Xiujiang , Cheng Gong , Lian Wei , Dong Shengjie , Zhao Yuchi , Qu Wenqing , Wu Hao
Published: May 2020

[Objective] To compare the mechanical characteristics of percutaneous long plate, percutaneous pubic superioris intramedullary screw and percutaneous pelvic anterior screw-rod system for the treatment of bilateral vertical pubic fractures to provide reference for clinical application. [Methods] A finite element model of pelvic anterior ring injury (bilateral vertical pubic fracture) was produced. The fractures were fixed with percutaneous long plate, percutaneous pubic superioris intramedullary screw, percutaneous pelvic anterior screw-rod system and their combination in 5 types of models. The fracture stability under vertical, bilateral and anterior-posterior load were quantified and compared based on the displacement of the hip joints’ midpoint as quantificational index of fracture stability. [Results] In condition of bilateral and anterior-posterior load, the vertical, bilateral and anterior-posterior displacement of the hip joints’ midpoint of different models were significantly different respectively. In general, the displacement of the 5 pelvic anterior ring fixation models were ranked from maximum to minimum as follows: long plate, pelvic anterior screw-rod system, combination of long plate and pelvic anterior screw-rod system, pubic superioris intramedullary screw and combination of pubic superioris intramedullary screw and pelvic anterior screw-rod system. [Conclusion] For the fixation in bilateral pubic fractures of pelvic injury, the percutaneous pubic superioris intramedullary screw was optimal, percutaneous pelvic anterior screw-rod system was the second choice, and percutaneous long plate ranked the third. The percutaneous pelvic anterior screw-rod system can significantly increase fixation stability of the percutaneous pubic superioris intramedullary screw and the percutaneous long plate.
Factors determining the choice of a career in geriatrics among students in geriatric in-hospital training: a single-center prospective study of 74 students
Authors: Nuss Valentine , Barben Jérémy , Laborde Caroline , Vovelle Jérémie , Deidda Martha , Mihai Anca-Maria , Putot Alain , Manckoundia Patrick
Published: May 2020

Background: To understand the reasons for the lack of attractiveness of the Diploma of Specialized Studies (DSS) in Geriatrics (DSSG), we conducted a study to identify the factors influencing medical students’ choice of their future specialty. In addition, we assessed the impact of in-hospital training (IHT) in the departments of our geriatric center on the students’ choice of their future specialty.Methods: We included all students who passed an IHT course in the geriatric center of our university hospital between 1 May 2018 and 31 October 2018. The data were collected using a questionnaire in two parts: one given before the IHT and the other after. The students were classified into two groups: those considering a career in geriatrics before IHT (GDSSG+) and those not considering it (GDSSG−). Results: Seventy-four students, aged a mean 22 years, were included. Of these students, 26%, were considering the possibility of a career in geriatrics before the IHT course (GDSSG+). This rate significantly increased to 42% after IHT (p=0.04). However, none of the students in GDSSG+ preselected geriatrics as their first option; general medicine was the most frequent option.For more than 92% of the students, the comprehensive care of geriatric patients was an asset. The main drawbacks were diagnostic and therapeutic limitations for 60% of the students, and managing aging, disability, and major neurocognitive disorders (MNCD) for 55%. After IHT, the view of geriatrics improved by 74%.Conclusion: Geriatric IHT improves students' opinions of geriatrics and significantly increases the number of students considering a potential career in geriatrics. However, geriatrics still suffers from a lack of prestige.
Comparative Evaluation of Six Molecular Assays based on RT-PCR and Cross Primer Isothermal Amplification for SARS-CoV-2 Detection
Authors: Wu Shuang , Shi Xiaolu , Chen Qiongcheng , Jiang Yixiang , Zuo Le , Wang Lei , Jiang Min , Lin Yiman , Fang Shisong , Peng Bo , Wu Weihua , Liu Hui , Zhang Renli , Kwan Patrick S.L. , Hu Qinghua
Published: May 2020

SARS-CoV-2 is a newly emerged coronavirus that was isolated from human infections in recent months. Since drugs and vaccines of Covid-19 are still being developed, accurate pathogen detection plays a crucial role in the current public health crisis. Quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay has been reliably used for the detection and confirmation of SARS-CoV-2 since the beginning of outbreak, whereas isothermal nucleic acid amplification based point of care automated assays has also been considered as a simpler and rapid alternative. However, since these assays have only been developed and applied for clinical use within a short timeframe, their analytical performance has not been adequately compared to-date. We describe a comparative study between a newly developed cross primer isothermal amplification (CPA) assay (Kit A) and five RT-PCR assays (Kits B to F), using clinical diagnosis as the reference standard to evaluate their sensitivity, specificity, predictive values and accuracy analysis. Clinical samples used (n=52) included throat swabs (n=30), nasal swabs (n=7), nasopharyngeal swabs (n=7) and sputum specimens (n=8), comprised of positive (n=26) and cleared cases (n=26) by clinical diagnosis. For the CPA assay (Kit A), the sensitivity, specificity, positive and negative predictive values and accuracy were 100%. Among the five RT-PCR kits, Kits B, C and F had good agreement with clinical diagnosis (Kappa≥0.75), Kits D and E were less congruent (0.4≤Kappa<0.75). Differences between all assays were statistically significant (P<0.001). The reproducibility of RT-PCR assays was determined using a positive sample that was verified by all assays, with standard deviations (SD) between 0.35 and 0.87, and coefficients of variation (CV) between 0.95% and 2.57%, indicating good reproducibility. To further evaluate the CPA assay (Kit A) compared to Kits B and F, throat swabs from close contacts of cases (n=200) were analyzed. All three kits identified the same positive samples and showed total agreement. This is the first comparative study to evaluate a CPA assay and RT-PCR assays for SARS-CoV-2 detection, which could serve as a reference for clinical laboratories and inform testing protocols amid the rapidly evolving COVID-19 pandemic.
Clinical symptoms, comorbidities and complications features in severe and non-severe patients with COVID-19: a systematic review and meta-analysis without cases duplication
Authors: Wang Zhufeng , Deng Hongsheng , Ou Changxing , Liang Jingyi , Wang Yingzhi , Jiang Mei , Li Shiyue
Published: May 2020

Background: The pandemic of COVID-19 posed a challenge to global healthcare. The mortality rates of severe cases range from 8.1% to 31.8%, and it is particularly important to identify risk factors that aggravate the disease.Methods: We performed a systematic review of the literature with meta-analysis, using 7 databases to assess clinical characteristics, comorbidities and complications in severe and non-severe patients with COVID-19. All the observational studies were included. We performed a random or fixed effects model meta-analysis to calculate the pooled proportion and 95% CI. Measure of heterogeneity was estimated by Cochran’s Q statistic, I2 index and P value.Results: 4881 cases from 25 studies related to COVID-19 were included. The most prevalent comorbidity was hypertension (severe: 33.4%, 95% CI: 25.4% - 41.4%; non-severe 21.6%, 95% CI: 9.9% - 33.3%), followed by diabetes (severe: 14.4%, 95% CI: 11.5% - 17.3%; non-severe: 8.5%, 95% CI: 6.1% - 11.0%). The prevalence of ARDS, AKI and shock were all higher in severe cases, with 41.1% (95% CI: 14.1% - 68.2%), 16.4% (95% CI: 3.4% - 29.5%) and 19.9% (95% CI: 5.5% - 34.4%), rather than 3.0% (95% CI: 0.6% - 5.5%), 2.2% (95% CI: 0.1% - 4.2%) and 4.1% (95% CI -4.8% - 13.1%) in non-severe patients, respectively. The death rate was higher in severe cases (30.3%, 95% CI: 13.8% - 46.8%) than non-severe cases (1.5%, 95% CI: 0.1% - 2.8%).Conclusions: Hypertension, diabetes and cardiovascular diseases may be risk factors for COVID-19 patients to develop into severe cases.
Rapid Identification of COVID-19 Severity in CT Scans through Classification of Deep Features
Authors: Yu Zekuan , Li Xiaohu , Sun Haitao , Wang Jian , Zhao Tongtong , Chen Hongyi , Ma Yichuan , Zhu Shujin , Xie Zongyu
Published: May 2020

Background: To implement the real-time diagnosis of the severity of patients infected with novel coronavirus 2019 (COVID-19) and guide the follow-up therapeutic treatment, We collected chest CT scans of 202 patients diagnosed with the COVID-19 from three hospitals in Anhui Province, China.Methods: A total of 729 2D axial plan slices with 246 severe cases and 483 non-severe cases were employed in this study. Four pre-trained deep models (Inception-V3, ResNet-50, ResNet-101, DenseNet-201) with multiple classifiers (linear discriminant, linear SVM, cubic SVM, KNN and Adaboost decision tree) were applied to identify the severe and non-severe COVID-19 cases. Three validation strategies (holdout validation, 10-fold cross-validation and leave-one-out) are employed to validate the feasibility of proposed pipelines. Results and conclusion: The experimental results demonstrate that classification of the features from pre-trained deep models show the promising application in COVID-19 screening whereas the DenseNet-201 with cubic SVM model achieved the best performance. Specifically, it achieved the highest severity classification accuracy of 95.20% and 95.34% for 10-fold cross-validation and leave-one-out, respectively. The established pipeline was able to achieve a rapid and accurate identification of the severity of COVID-19. This may assist the physicians to make more efficient and reliable decisions.
Time to Lactate Measurement Affects Efficacy of Initial Lactate on Mortality in critically ill patients with sepsis.
Authors: Luo Xueying , Zheng Xiaobo , Rao Xi , Li Ya , Zheng Sujing , Chen Weicai , He Jinsong
Published: May 2020

Background: Evidence regarding the effect of time to lactate measurement on the relationship between the initial lactate level and mortality is limited. We aimed to investigate the relationships between time to lactate measurement, initial lactate level, and in-hospital mortality in critically ill patients with sepsis.Methods and Results: Of the 14339 eligible adult patients with recognized sepsis upon admission to the ICU based on the MIMIC-III database, the median value of initial lactate was 1.70 mmol/L (interquartile range [IQR] 1.20-2.80), and its detection time was 3.50 hours ([IQR] 1.31-10.24). The results of fully adjusted multivariate analyses demonstrated that lactate was positively associated with in-hospital mortality (odds ratio: 1.126, 95% confidence interval: 1.090 to 1.163, P<0.001), and there was an increase in the odds of death with hourly delays in lactate measurement (OR: 1.006, 95% CI: 1.004 to 1.008, P<0.001). In stratified analyses, delays in lactate measurement significantly interfered with the impact of increased lactate level on mortality (P-value for interaction<0.001). The hospital mortality rate substantially increased by 43.5% for each unit increase in lactate when measurement was delayed by 24 hours (OR: 1.435, 95% CI: 1.260 to 1.635, P<0.001).Discussion: The association of initial lactate with in-hospital mortality is likely to vary with delays in detection time (grouping based on the “1-hour bundle”) in critically ill patients with recognized sepsis upon admission to the ICU.
WITHDRAWN: PADI4 regulates osteosarcoma proliferation primarily via Wnt/β-catenin and MEK/ERK signaling pathway
Authors: Guo Jianping , Yin Lei , Zhang Xuezhong , Su Peng , Zhai Qiaoli
Published: May 2020

Background
Peptidylarginine deiminase 4 (PADI4), an important modification enzyme of proteins, has received increased attention for its role in tumorigenesis of several human cancers. However, the effect of PADI4 on osteosarcoma remains largely unknown. Here, we evaluated the impact and mechanism of PADI4 on osteosarcoma proliferation.
Methods
Impact of PADI4 on proliferation of osteosarcoma cells is detected by the method of CCK8 and colony formation assay. Expression of PADI4 as well as Wnt/β-catenin and MEK/ERK signaling markers after knocking down or ectopically expressing PADI4 or PADI4 inhibitor treatment is investigated by Western blot and RT-PCR. Then we investigated relevance of the expression level of the PADI4 in osteosarcoma samples and paired normal tissues by Western blot and RT-PCR. To further confirm whether PADI4 affect osteosarcoma tumorigenesis in vivo, we performed tumor formation experiments in nude mice.
Results
Firstly, ectopically expressing PADI4 showed positive regulation on colony formation capacity of osteosarcoma cells. Secondly, PADI4 stimulated Wnt/β-catenin and MEK/ERK signaling in osteosarcoma cells. Thirdly, PADI4 is highly expressed in osteosarcoma samples compared with normal tissues. In vivo experiment also verified the positive effect of PADI4 on the growth of transplanted tumors in nude mice.
Conclusions
Taken together, our results revealed PADI4 promoted proliferation of osteosarcoma via Wnt/β-catenin and MEK/ERK signaling pathway. This study may expand our understanding of osteosarcoma tumorigenesis and identify PADI4 as a potential target for diagnosis and treatment of osteosarcoma.
Association between DPP-4 inhibitors and events of colorectal and liver cancers in patients with diabetes receiving second-line agents: a nested case-control study
Authors: Chou Chu-Lin , Juan Shu-Hui , Chen Hsi-Hsien , Kao Chih-Chin , Wu Yueh-Lin , Yeh Shu-Ching , Chen Li-Ying , Chen Jin-Shuen , Chien Li-Nien , Fang Te-Chao
Published: May 2020

Background and aim:

Several studies showed plasma dipeptidyl peptidase-4 (DPP4) levels were significantly lower in patients with colorectal and liver cancers, and animal studies also showed DPP4 inhibitors (DPP4is) have procarcinogenic effects in colorectal cancer. The aims of this study were to investigate the association between cumulative defined daily dose (cDDD) of DPP4is exposure and risks of liver and colorectal cancers in patients with type 2 diabetes mellitus.
Methods

In this nested case-control study, we identified 268,520 patients with diabetes receiving DPP4is as second-line agents between March 1, 2009, and December 31, 2013, from Taiwan’s National Health Insurance Research Database, Taiwan Cancer Registry, and National Death Registry of Taiwan. Of these, 948 and 990 patients newly were diagnosed with liver and colorectal cancer, respectively. The amount of DPP4is were divided into three groups (low, medium, and high) based on the interquartile range of the cDDD of the DPP4is. Results: The data showed that the low cDDD of DPP-4is was associated with a reducing risk of colorectal cancer [adjusted odds ratio (OR), 0.49; 95% CI, 0.32–0.75; P = 0.001]. However, the high cDDD of DPP-4is was associated with an increasing risk of colorectal cancer (adjusted OR, 1.86; 95% CI, 1.32–2.61; P < 0.001). No association between DPP4is use and liver cancer risk was observed.
Conclusions

The novel finding of this nested case study revealed a J-shaped association between the cDDD of DPP-4is and colorectal cancer risk, but not liver cancer risk. A large-based longitudinal investigation is necessary to determine whether long-term DPP4is exposure increase colorectal cancer risk.
Appropriateness of Antibiotic use for the Management of Acute Diarrhea Among Under-Five Children Treated at Primary Care Centers in Northwest Ethiopia: A Cross-Sectional Study
Authors: Abegaz Sumeya Tadesse , Zeleke Addisu Jember , Tesfaye Zelalem Tilahun
Published: May 2020

Background Acute diarrhea management is solely aimed at fluid replacement and nutritional support while antibiotics have a very limited role. Antibiotic treatment is recommended only for bloody diarrhea (dysentery), cholera and invasive bacterial diarrhea. This study is launched to assess the appropriateness of antibiotic use for the management of acute diarrhea among under-five children in Gondar town primary care centers.Methods Institutional based cross-sectional study was conducted in three primary care centers located in Gondar town, Northwest Ethiopia. Children aged from 2–59 months who visited the three primary care centers from September 12, 2015 to September 10, 2016 and received treatment for acute diarrhea were included in the study. We selected 176 cases from Azezo Health Center, 166 from Poly Health Center and 80 from Woleka Health Center. Cases were drawn using systematic random sampling technique. The findings of the study were summarized using tables and figures; binary logistic analysis was used to identify association between the independent and outcome variables at 95% confidence level where p < 0.05 was considered as statistically significant.Results The mean age of the study participants was 19.1 ± 12.8 months. The majority (60.8%) were males. Appropriate antibiotic use was recorded in less than half (47.2%) of the study subjects. Almost all (98.1%) of children subjected to inappropriate antibiotic use were those with watery diarrhea treated with antibiotics. Out of 253 children who received antidiarrheal antibiotics 202 (79.8%) had acute watery diarrhea which should not be treated with antibiotics. Children diagnosed with acute watery diarrhea were less likely to receive treatment qualified as appropriate antibiotic use [AOR: 0.003 (0.001,0.017)]. Conversely, receiving no antibiotic [AOR: 391.00 (92.46, 1653.37)] and prescriber’s profession of Clinical Nurse [AOR: 3.57 (1.02, 12.51)] were positive predictors for appropriate antibiotic use.Conclusion The findings of the study confirm the prevalence of widespread inappropriate antibiotic use on under-five children presenting with acute diarrhea. The findings can be used by stakeholders as input for promoting appropriate antibiotic use in the healthcare system as well as to deter antimicrobial resistance.
Next-generation sequencing of tissue and circulating tumor DNA: Resistance mechanisms to EGFR targeted therapy in a cohort of patients with advanced non-small cell lung cancer
Authors: Zhang Yujun , Xiong Liwen , Xie Fangfang , Zheng Xiaoxuan , Li Ying , Zhu Lei , Sun Jiayuan
Published: May 2020

Background

Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) has been considered as an effective treatment in epidermal growth factor receptor-mutant (EGFR-mutant) advanced non-small cell lung cancer (NSCLC). However, most patients develop acquired resistance eventually. Here, we compared and analyzed the genetic alterations between tissue assay and circulating tumor DNA (ctDNA), and further explored the resistance mechanisms after EGFR-TKI treatment.
Methods

Amplification refractory mutation system-polymerase chain reaction (ARMS-PCR), Cobas® ARMS-PCR and next-generation sequencing (NGS) were performed on tissue samples after pathological diagnosis. Digital droplet PCR (ddPCR) and NGS were performed on plasma samples. The association between genetic alterations and clinical outcomes was analyzed retrospectively.
Results

Thirty-seven patients were included. The success rate of re-biopsy was 91.89% (34/37). The total detection rate of EGFR T790M was 62.16% (23/37) and the consistency between tissue and ctDNA was 78.26% (18/23). Thirty-four patients were analyzed retrospectively. Twenty-four patients harbored concomitant mutations. Moreover, tissue re-biopsy at resistance showed 21 patients (21/34, 61.76%) had concomitant T790M mutation, 4 with MET amplification and 4 with PIK3CA mutation. Patients with T790M mutation (p = 0.010 & p = 0.017) or third-generation EGFR-TKI treatment (p < 0.0001 & p = 0.073) showed better progression-free survival (PFS) and overall survival (OS). Interestingly, concomitant genetic alterations were significantly associated with a worse prognosis for patients with T790M mutation receiving third-generation EGFR-TKIs (p = 0.037).
Conclusions

Multi-platforms are feasible and highly consistent for re-biopsy after EGFR-TKI resistance. Concomitant genetic alterations may be associated with a poor prognosis for patients with T790M mutation after third-generation EGFR-TKIs.
Trial Registration:

The clinical trial registration was carried out on ClinicalTrials.gov. (NCT03309462), registered on September 1st 2017. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0007G1B&selectaction=Edit&uid=U0001WUU&ts=2&cx=frpicv
Stimulation of Insulin Signaling Reverses Inflammation-Induced Cone Death in Retinal Detachment
Authors: CONART Jean-Baptiste , Blot Guillaume , Augustin Sébastien , Roubeix Christophe , Beguier Fanny , Charles-Messance Hugo , Touhami Sara , Sahel José-Alain , Berrod Jean-Paul , Guillonneau Xavier , Delarasse Cécile , Sennlaub Florian
Published: May 2020

Background Rhegmatogenous retinal detachment (RD) involving the macula is a major cause of visual impairment despite high surgical success rate, mainly because of cone death. We and others have shown that cone loss occurs secondary to chronic inflammation in many retinal diseases, including age-related macular degeneration and retinitis pigmentosa. We here investigated the yet unknown mechanisms of inflammation-induced cone death in RD.Methods Vitreous samples from patients with RD and from control patients with macular hole were analyzed to characterize the inflammatory response to RD. A mouse model of RD and retinal explants culture were then used to explore the mechanisms leading to cone death.Results Analysis of vitreous samples shows that RD induces a marked inflammatory response with increased cytokine and chemokine expression in humans, which is closely mimicked by experimental murine RD. In this model, we demonstrate that myeloid cells and T-lymphocytes directly contribute to cone loss, as the inhibition of their accumulation by Thrombospondin 1 increased cone survival. We show that cones are highly dependent on glucose and insulin signaling for survival in vitro and that insulin, and the insulin sensitizers rosiglitazone and metformin, prevent RD-induced cone loss in vivo, despite the persistence of inflammation.Conclusion Our results describe a new mechanism by which inflammation, likely through a combination of competition for glucose and the inhibition of insulin signaling, promotes cone death in RD. Therapeutic inhibition of inflammation and stimulation of insulin signaling might prevent RD-associated cone death until the RD can be surgically repaired and improve visual outcome after RD.Trial registration: ClinicalTrials.gov Identifier NCT03318588
Crowdsourcing Framework for QoE-Aware SD-WAN
Authors: Ellawindy Ibtihal , Heydari Shahram Shah
Published: May 2020

The exponential increase in bandwidth-sensitive multimedia traffic on the Internet has created new challenges and opportunities. With the shifting focus from service availability to service quality, there is a need to have quality management measures to serve the high needs of efficient transmission and delivery in time-constrained environments over IP networks. Quality of Experience (QoE) is now considered the most important measure to achieve the twin goals of application efficiency and user satisfaction from a user perspective. In this paper, we propose a framework that can be used to collect real-time QoE feedback through crowdsourcing and forward it to SD-WAN controllers to enhance streaming routes based on real-time user quality perceptions. We analyze how QoE can be affected by different network conditions, and how different streaming protocols compare against each other when the network parameters change dynamically. We compare the real-time user feedback to predefined network changes to measure if participants will be able to identify all degradation events, and to examine which combination of degradation events are noticeable to the participants. These QoE timestamped feedback is sent back to the SD-WAN controller continuously in order to locate problems and bottlenecks in the current service paths and to enable network controllers to take corrective action by rerouting the streamed traffic. Our aim is to demonstrate that real-time QoE feedback can enhance cloud-based services and can adjust services quality based on real-time, active participants’ interaction.
Advances in Research on the circRNA-miRNA-mRNA regulatory network in lung adenocarcinoma by analysis of microarray data
Authors: Yao Qing , He Yong-Lai , Pang Li-Juan , Wang Ning , Dong Shuang-Shuang , Shi Mei Er Tu He Ta Mi , Feng Xiao , Zhou Wen-Hu , Qi Yan
Published: May 2020

Background: The present researches indicate that circular RNAs (circRNAs) play pivotal roles in the generation and development of human cancers. However, function of circRNAs in lung adenocarcinoma is still unknown. Herein, we focused our study on the regulation mechanism of circRNAs in lung adenocarcinoma (LUAC)Methods: CircRNAs-related data can be downloaded from Gene Expression Omnibus(GEO) microarray databases. Relevant expression data of miRNAs and mRNAs were obtained from The Cancer Genome Atlas (TCGA) databases. The differentially expressed circRNAs (DEcircRNAs) were obtained by the robust rank aggregation method, and constructed a ceRNA network with circRNA-miRNA pairs and miRNA-mRNA pairs. The function and pathway enrichment of different genes were analyzed, and the protein-protein interaction (PPI) was predicted by String software, and the subnetwork management module was constructed by MCODE plugin. The differentially expressed mRNAs (DEmRNAs) were used to establish survival analysis by R software.Results: A total of 19 up-regulated circRNAs, 45 down-regulated circRNAs, 98 up-regulated miRNAs, 18 down-regulated miRNAs, 2002 up-regulated mRNAs, and 553 down-regulated mRNAs were obtained in lung adenocarcinoma. The circRNA-miRNA-mRNA network was constructed by six circRNAs (hsa_circ_0003528, hsa_circ_0004315, hsa_circ_0005699, hsa_circ_0002588, hsa_circ_0005777, hsa_circ_0027033), 19 miRNAs and 33 mRNAs. GO and KEGG pathway analysis indicated that DEmRNAs might be related to the progression of LUAC. The PPI network was constructed and four hub genes (CEP55, CHEK1, CDC25A, KIF23) were obtained from the network, and four hub genes were found to be associated with the same miRNA and circRNA, including hsa_circ_0004315/hsa-miR-195/CEP55, CHEK1, CDC25A, KIF23. Three hub genes (CEP55, CHEK1, KIF23) were significantly associated with LUAC survival and prognosis, and the overall survival rate of lung adenocarcinoma was decreased in high-expression genes compared with low-expression genes.Conclusion: Our finding indicated that circRNA-miRNA- mRNA axis paly key role in the pathogenesis of lung adenocarcinoma, and some circRNAs could be considered as a biomarker and target for the diagnosis and therapy of LUAC patients.