bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of standard and semantically-augmented distance metrics for neurology patients
Authors: Hier Daniel B , Kopel Jonathan , Brint Steven U , II Donald C Wunsch , Olbricht Gayla R , Azizi Sima , Allen Blaine
Published: August 2020

Background: Patient distances can be calculated based on signs and symptoms derived from an ontological hierarchy. There is controversy as to whether patient distance metrics that consider the semantic similarity between concepts can outperform standard patient distance metrics that are agnostic to concept similarity. The choice of distance metric can dominate the performance of classification or clustering algorithms. Our objective was to determine if semantically augmented distance metrics would outperform standard metrics on machine learning tasks.Methods: We converted the neurological findings from 382 published neurology cases into sets of concepts with corresponding machine-readable codes. We calculated patient distances by four different metrics (cosine distance, a semantically augmented cosine distance, Jaccard distance, and a semantically augmented bipartite distance). Semantic augmentation for two of the metrics depended on concept similarities from a hierarchical neuro-ontology. For machine learning algorithms, we used the patient diagnosis as the ground truth label and patient findings as machine learning features . We assessed classification accuracy for four classifiers and cluster quality for two clustering algorithms for each of the distance metrics.Results: Inter-patient distances were smaller when the distance metric was semantically augmented. Classification accuracy and cluster quality were not significantly different by distance metric.Conclusion: Although semantic augmentation reduced inter-patient distances, we did not find improved classification accuracy or improved cluster quality with semantically augmented patient distance metrics when applied to a dataset of neurology patients. Further work is needed to assess the utility of semantically augmented patient distances.
Detailed severity assessment of Cincinnati Prehospital Stroke Scale to detect large vessel occlusion in acute ischemic stroke
Authors: Tárkányi Gábor , Csécsei Péter , Szegedi István , Fehér Evelin , Annus Ádám , Molnár Tihamér , Szapáry László
Published: August 2020

Background

Selecting stroke patients with large vessel occlusion (LVO) based on prehospital stroke scales could provide a faster triage and transportation to a comprehensive stroke centre resulting a favourable outcome. We aimed here to explore the detailed severity assessment of Cincinnati Prehospital Stroke Scale (CPSS) to improve its ability to detect LVO in acute ischemic stroke (AIS) patients.

Methods

A cross-sectional analysis was performed in a prospectively collected registry of consecutive patients with first ever AIS admitted within 6 hours after symptom onset. On admission stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) and the presence of LVO was confirmed by computed tomography angiography (CTA) as an endpoint. A detailed version of CPSS (d-CPSS) was designed based on the severity assessment of CPSS items derived from NIHSS. The ability of this scale to confirm an LVO was compared to CPSS and NIHSS respectively.

Results

Using a ROC analysis, the AUC value of d-CPSS was significantly higher compared to the AUC value of CPSS itself (0.788 vs. 0.633, p <0.001) and very similar to the AUC of NIHSS (0.795, p=0.510). An optimal cut-off score was found as d-CPSS≥5 to discriminate the presence of LVO (sensitivity: 69.9%, specificity: 75.2%).

Conclusion

A detailed severity assessment of CPSS items (upper extremity weakness, facial palsy and speech disturbance) could significantly increase the ability of CPSS to discriminate the presence of LVO in AIS patients.
Adolescent and non-consensual anal sexual debut among Chinese men who have sex with men: a cross-sectional study
Authors: Tang Weiming , Wang Yehua , Huang Wenting , Wu Dan , Yang Fan , Xu Yongshi , Ong Jason J. , Fu Hongyun , Yang Bin , Wang Cheng , Ma Wei , Wei Chongyi , Tucker Joseph D.
Published: August 2020

Background: Adolescent sexual debut and non-consensual sex have been linked to higher sexual risk and STI infection in adulthood among men who have sex with men (MSM) in high-income countries. This study aimed to examine adolescent and non-consensual anal sexual debut among Chinese MSM and to evaluate factors associated with adolescent sexual debut and non-consensual anal sex.Methods: A cross-sectional study was conducted recently among Chinese men assigned male sex at birth, ≥18 years old, and who had ever engaged in anal sex with a man. Participants answered questions regarding socio-demographics, condomless sex, age at anal sexual debut with a man, and whether the first anal sex was consensual. Factors associated with an adolescent sexual debut (<18 years old) and non-consensual sex at sexual debut were evaluated. We defined adolescent sexual debut as having anal sex with another man at 17 years old or younger, and the participants were asked whether their first male-to-male anal sex was non-consensual.Results: Overall, 2031 eligible men completed the survey. The mean age of sexual debut was 20.7 (SD=4.3) years old. 17.6% (358/2031) of men reported adolescent sexual debut, and 5.0% (101/2031) reported a non-consensual sexual debut. The adolescent sexual debut was associated with having more male sexual partners (adjusted OR 1.10, 95% CI 1.06–1.15) and condomless anal sex in the last three months (AOR=1.71, 95% CI 1.34-2.18). MSM whose sexual debut was non-consensual were more likely to have condomless anal sex (AOR=1.76, 95% CI 1.17-2.66), and to have reported an adolescent sexual debut (AOR=2.72, 95% CI 1.75-4.21).Conclusions: Many Chinese MSM reported adolescent sexual debut and non-consensual sex, both of which are associated with sexual risk behaviors and drive STI transmission. These findings highlight the need for designing tailored interventions for MSM who experienced adolescent sexual debut and non-consensual sex at debut.
Impact of Prior Cancer History on Outcomes in Thymoma
Authors: Wu Shilong , Liu Mengyang , Cui Weixue , Peng Guilin , He Jianxing
Published: August 2020

Background

Thymoma is an uncommon intrathoracic malignant tumor and has a long natural history. It is uncertain whether the survival of thymoma patient is affected by prior cancer history. Finding out the impact of a prior cancer history on thymoma survival has important implications for both decision making and research.

Method

The Surveillance, Epidemiology, and End Results (SEER) database was queried for thymoma patients diagnosed between 1975 and 2015. Kaplan-Meier methods and Cox proportional hazards model were used to analyze overall survival across a variety of stages, age, and treatment methods with a prior cancer history or not.

Results

A total of 3604 patients with thymoma were identified including 507 (14.1%) with a prior cancer history. The 10-year survival rate of patients with a prior cancer history (53.8%) was worse than those without a prior cancer history (40.32%, 95%CI 35.24-45.33, P < 0.0001). However,

adjusted analyses showed that the impact of a prior cancer history was heterogenous across age and treatment methods. In subset analyses, prior cancer history was associated with worse survival among patients who were treated with chemoradiotherapy (HR: 2.80, 95% CI: 1.51-5.20, P = 0.001) and age ≤ 65 years (HR: 1.33, 95%CI: 1.02-1.73, P = 0.036).

Conclusions

Prior cancer history provides an inferior overall survival for patients with thymoma. But it does not worsen the survival in some subgroups and these thymoma patients should not be excluded from clinical trials.
Integrated analysis of the metabolome and transcriptome in different developmental stages of Cerasus humilis peel coloration
Authors: Ji Xiaolong , Ren Jing , Sun Lijiao , Lang Shaoyu , Zhu Liwei , Song Xing Shun
Published: August 2020

Background: Cerasus humilis is a unique dwarf shrub and fruit color is an important trait in the species. In this study, we evaluated the transcriptomic and metabolomic profiles of the plant at different developmental stages to elucidate the mechanism underlying color formation.Results: In a metabolomics analysis, 16 anthocyanin components were identified at different developmental stages, and high levels of cyanidin O-syringic acid and pelargonidin 3-O-beta-d-glucoside (callistephin chloride) were correlated with the reddening of the fruit peel. Additionally, transcriptome analysis showed that most anthocyanin biosynthetic genes and two MYB transcription factors were significantly up-regulated. qRT-PCR results for these differentially expressed genes were generally consistent with the high-throughput sequencing. A co-expression analysis revealed that ANS and UFGT play keys role in pigmentation. Conclusions: These findings provide insight into the mechanisms underlying anthocyanin accumulation and coloration during fruit peel development, providing a basis for the breeding of anthocyanin-rich C. humilis cultivars.
Retinal Vascular Changes with Non-Arteritis Anterior Ischemic Optic Neuropathy Assessed with IVAN Analysis
Authors: Zhang Longli , Hei Kaiwen , Ke Yifeng , Zhang Heng , Li Xiaorong , Yang Qianhui
Published: August 2020

Background

To assess the vascular changes associated with non-arteritis anterior ischemic optic neuropathy (NAION) by using integrative vessel analysis (IVAN) and risk factors associated with NAION.
Methods

We performed a case-control study of 120 patients, including 40 NAION patients during July 2015 to July 2019. Patients were divided into Normal, hypertension and NAION groups. IVAN was conducted to evaluate the caliber of retinal vessels. In addition, we also analyzed risk factors (age, gender and BMI) to identify their association with NAION.
Results

84 women and 36 men were involved in our study, the average age was 58 ± 9.98 years. CRAE, CRVE and AVR in the whole patients were 154.54 ± 21.53 µm, 252.22 ± 15.88 µm and 0.64, respectively. ANOVA analysis showed significant difference of CRAE [F (2,116) = 4.203, p = 0.017], CRVE [F (2,116) = 49.91, p < 0.001] and AVR [F (2,116) = 13.81, p < 0.0001] between each group, NAION group had wider CRAE and CRVE, while smaller AVR. BMI value showed negative correlation with CRAE in NAION group, while positively with CRVE.
Conclusion

Retinal vascular caliber can be used as an indicator to evaluate the NAION. Our study suggested that an assessment of retinal vascular caliber may offer insights into the development of NAION.
Evaluation and management of obstetric genital fistulas treated at a pelvic floor centre in Germany
Authors: Reisenauer Christl , Amend Bastian , Falch Claudius , Abele Harald , Brucker Sara Yvonne , Andress Jürgen
Published: August 2020

Background: Obstetric genital fistulas are an uncommon condition in developed countries. We evaluated their causes and management in women treated at a German pelvic floor centre.Methods: Women who had undergone surgery for obstetric genital fistulas between January 2006 and June 2020 were identified and their records were reviewed retrospectively.Results: 11 out of 40 women presented with genitourinary fistulas, and 29 suffered from rectovaginal fistulas. In our cohort the genitourinary fistulas were more common in multiparous (9/11) and the rectovaginal fistulas in primiparaous women (24/29). The majority of the genitourinary fistulas were at a high anterior position in the vagina and all rectovaginal fistulas were at a low posterior position. While all genitourinary fistulas were successfully closed, rectovaginal fistula closure was achieved in 88.65%. Women who suffered from rectovaginal fistulas and were at high risk of recurrence or postoperative functional discomfort and desired another child, we recommended the fistula repair in context of a subsequent delivery. For the first time, pregnancy related changes of the vaginal wall were used to optimize the success rate of a fistula closure.Conclusions: In developed countries, the birth itself can lead to injury-related genital fistulas. As fistula repair lacks evidence-based guidance, their management has to be tailored to the underlying pathology and the surgeonʼs experience. Attention should be directed towards preventive obstetric practice and adequate perinatal and postpartum care. Even if vesicovaginal fistulas occur rarely, in case of urinary incontinence after delivery, attention should be paid to the patient and a vesicovaginal fistula should be ruled out.Trial registration: retrospectively registered, DRKS 00022543, 28.07.2020
Analyzing Twitter Data to Evaluate the People’s Attitudes to Public Health Policies and Events in the Era of COVID-19
Authors: Tsai Meng-Hsiu , Wang Yingfeng
Published: August 2020

Background: In the era of a pandemic like COVID-19, monitoring the sentimental changes of the population is an urgent need, especially for the policy makers of the public health. A possible solution is to build a fast and low-cost surveillance system by using the sentiment analysis of Twitter data. Unfortunately, choosing a suitable sentiment classification model is still challenging. The general pre-trained model may be insensitive to the new specific terms of the pandemic. The early-trained model may have a bias issue due to the incomplete specific corpus. Although it is reasonable to assume the late-trained model is relatively reliable, it is usually available months after a pandemic begins. Methods: This paper conducts the sentiment analysis of Twitter data and compares different models. Furthermore, we propose a strategy for using the pre-trained, early-trained, and latetrained models in a surveillance system based on Twitter data. The first two models can be used together in the early stage, while the last model can be used in the late stage. This study also analyzes the relationship between the sentimental changes of COVID-19-related Twitter data and the public health policies and events. Results: Our results indicate that applying the pre-trained model to preprocessing early training samples may improve the early-trained model. Both models can work together by making up each other in the surveillance system in the early stage. Conclusions: A fast and low-cost surveillance system is critical to the policy makers of the public health in a pandemic. This work uses the sentiment analysis of Twitter data to evaluate people’s attitudes to public health policies and events. We propose a strategy to make the surveillance system effective since the early stage. This study also connects the sentimental changes of COVID19-related Twitter data to the public health policies and events.
Health System Preparedness in Tackling the COVID-19 in Nepal: a Qualitative Study Among Frontline Healthcare Workers and Policymakers
Authors: Shrestha Nipun , Mishra Shiva Raj , Ghimire Saruna , Gyawali Bishal , Marahatta Sujan Babu , Maskey Smriti , Baral Sushila , Shrestha Nilima , Yadav Rakesh , Adhikari Bipin
Published: August 2020

BackgroundRapidly growing coronavirus disease 2019 (COVID-19) pandemic has brought unprecedented challenges to the health system in Nepal. The main objective of this study was to explore the characteristics and drivers of the health system preparedness towards COVID-19 and its impacts on frontline health care workers (HCWs) in Nepal.MethodsSemi-structured interviews (SSIs) were conducted among 32 HCWs who were involved in clinical care of COVID-19 patients and four policymakers who were responsible for COVID-19 control and management at central and provincial level. Participants were included from all seven provinces of Nepal. All SSIs were conducted through telephone or internet based tools such as Zoom and Skype. All interviews were audio-recorded, transcribed into English, and coded using inductive and deductive approaches.ResultsBoth HCWs and policymakers reported failure to initiate pre-emptive control measures at the early stages of the outbreak as the pivot in pandemic control. Although several measures were rolled out when cases started to appear, the overall health system preparedness was low. Specifically, there was inadequate personal protective equipment for HCWs, insufficient isolation beds for patients, poor coordination between the three tiers of governance, and poor engagement of the private sector. Additionally, HCWs experienced various degrees of stigma because of their profession and yet were able to maintain their motivation to continue working in the forefront.ConclusionThis study identified poor preparedness of the health system in the course of Nepal's COVID-19 response embedded in the governance. Specifically, the lack of human resources, inadequate logistic chain management and laboratory facilities for testing COVID-19 appeared to have jeopardized the health system preparedness and escalated the pandemic in Nepal. Despite the poor preparedness, and health and safety concerns, HCWs maintained their motivation. Urgent efforts are required to reform the governance and coordination mechanism in addition to incentivizing the HCWs for the current and future pandemics.
Shared Genetic Links Between Amyotrophic Lateral Sclerosis and Obesity-Related Traits: A Genome-Wide Association Study
Authors: Li Chunyu , Ou Ruwei , Gu Xiaojing , Wei Qianqian , Shang HuiFang
Published: August 2020

Background: Epidemiological and clinical studies have suggested comorbidity between amyotrophic lateral sclerosis (ALS) and obesity-related traits. However, little is known about their shared genetic architecture.Objective: To examine whether there exist genetic enrichment between ALS and eleven obesity-related traits, including body mass index (BMI), waist hip ratio, body fat percentage (BFP), birth weight, triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), type 2 diabetes (T2D), fasting glucose, fasting insulin, and identify shared loci among them.Methods: Using the conditional false discovery rate (FDR) statistical framework, we analyzed genome wide association summary statistics for ALS (n=80610) and obesity-related traits, and further conducted functional enrichment analysis.Results: Robust genetic enrichment was observed for ALS conditional on BMI, BFP, HDL-C, LDL-C and T2D, but minimal enrichment on the other traits. 9 shared genetic loci with conjunctional FDR < 0.05 was identified, among which 6 were replicated in a second ALS cohort, including rs3849942 (C9orf72), rs170663 (G2E3), rs8018993 (SCFD1), rs978220 (ATXN3), rs62333164 (CLCN3) and rs12603276 (GGNBP2). We further identified GGNBP2 as a novel potential ALS risk gene, by integrating cis-expression quantitative trait loci analysis in human brain tissue and summary-data-based Mendelian randomization analysis. Functional analysis indicated the shared risk genes were involved in pathways membrane trafficking and vesicle-mediated transport.Conclusions: Our findings demonstrate selective genetic overlap between ALS and obesity-related traits, and identified new shared risk loci, including novel potential ALS risk gene GGNBP2. These results provide better understanding for the pleiotropy of ALS and have implications for future therapeutic trials.
Which factors may influence the implementation of drug dispensing in community pharmacies? A qualitative study
Authors: Cerqueira-Santos Sabrina , Rocha Kérlin Stancine Santos , Araújo Dyego Carlos Souza Anacleto , Júnior Genival Araujo Santos , Menezes Pedro Wlisses dos Santos , Sanchez Júlia Mirão , Mesquita Alessandra Rezende , Lyra Divaldo
Published: August 2020

The authors have withdrawn this preprint due to author disagreement.
Determinants of HIV Testing Among Men Living in Rural Areas: Evidence from Ethiopian Population–Based Household Survey, 2016.
Authors: Worku Getasew Taddesse
Published: August 2020

Background: Ethiopia is one of the high-burden HIV Country with low HIV test uptake. Although HIV is more prevalent among women in Sub-Saharan countries, HIV testing among men is equally important to end the HIV epidemic. Objective: To investigate the prevalence and determinants of HIV testing among rural men using Ethiopian Demographic and Health Survey (EDHS) 2016 data.Method: This study used EDHS 2016 data. The sample size for this study was 10,187 rural men. Descriptive statistics analysis to know sample distribution and bivariable and multivariable logistic regression to identify associated factors with rural men's HIV testing status. All analyses were performed using the complex sample analysis procedure of the SPSS version 20.0 to account for the multistage sampling.Result: Overall, 40.3% of rural men were ever been tested for HIV. In the multivariable analysis, Being aged, 31-44 [Adjusted Odds Ratio (AOR:) 1.12; 95% CI: 1.01-1.42], living in developed regions (AOR: 1.43; 95% CI: 1.09-1.88), engaged in non-agricultural sector (AOR: 1.27; 95% CI: 1.05-1.52), being Muslim (AOR: 2.07; 95% CI: 1.67-2.67), and having comprehensive knowledge about HIV (AOR: 1.31; 95% CI: 1.12-1.54) were positively associated with HIV testing. In the contrary, belonging to medium (AOR: 0.56; 95% CI:0.47-0.67) and rich (AOR: 0.67; 95% CI:0.56-0.80) wealth status, attending primary (AOR: 0.21; 95% CI: 0.16-0.28)) and secondary (AOR: 0.31; 95% CI: 0.25-0.35) education, having first sexual debut at age of <=17 (AOR: 0.26;95% CI: 0.19-0.93), perceived stigma towards HIV patients (AOR: 0.67; 95% CI: 0.47-0.93) and have not health insurance coverage(AOR: 0.54; 95% CI: 0.42-0.69) were negatively associated with HIV testing among rural men.Conclusion: HIV testing of rural men was very low. Socio-economic and other push factors like comprehensive knowledge about HIV, Perceived stigma towards HIV patients, and having health insurance coverage were found the determinant of testing among rural men. The Ethiopian government with its stakeholders should focus on rural men who least likely to get HIV testing. The Awareness building program about HIV and HIV testing should be initiated to encourage rural men to visit health facilities and take the test.
A Multilevel Modelling of Barriers to Healthcare Access and Healthcare Seeking for Childhood Illnesses Among Childbearing Women in Burundi
Authors: Ahinkorah Bright Opoku , Seidu Abdul-Aziz , Hagan John Elvis Elvis , Budu Eugene , Mohammed Aliu , Adu Collins , Ameyaw Edward Kwabena , Adoboi Faustina , Schack Thomas
Published: August 2020

BackgroundPoor health seeking behaviour continue to be major challenge in accessing healthcare in sub-Saharan Africa despite the availability of effective treatment for most childhood illnesses. The current study investigated the barriers to healthcare access and health seeking for childhood illnesses in Burundi.Methods The study utilized data from the 2016-17 Burundi Demographic and Health Survey (BDHS). A total of 11,828 childbearing women who had complete information on all the variables of interest were included in our study. The outcome variable for the study was healthcare seeking for childhood illnesses. The data were analyzed using STATA version 14.2 for windows. Chi-square test of independence and a multilevel modelling were carried out to generate the results. Statistical significance was pegged at 95% confidence intervals (CIs).Results Overall, 80.55% of women in Burundi sought care for their children’s illness. We found that women who perceived getting money for medical care for self as a big problem [AOR=0.82; CI=0.73-0.91] and considered going for medical care alone as a big problem [AOR=0.84; CI=0.73-0.96], had lower odds of seeking healthcare for their children, compared to those who considered these indicators as not a big problem. The results also showed that cohabiting mothers [AOR=0.86; CI=0.76-0.96], those taking healthcare decisions alone [AOR=0.83; CI=0.71-0.97], women in female headed households [AOR=0.85;CI=0.74-0.98], women with children larger [AOR=0.86;CI=0.77-0.96] and smaller than average [AOR=0.76;CI=0.67-0.87], single birth children [AOR=0.65; 0.47-0.89], and women in rural areas [AOR=0.79; CI=0.63-0.99] had lower odds of seeking care for their children’s illness.ConclusionFindings suggest that Burundi should strengthen maternal health care regarding women’s healthcare accessibility and health seeking behaviours, especially with residential consideration and among women from the poorest wealth quintile, those cohabiting and those with lower parity. The Burundian government through multi-sectoral partnership should strengthen health systems (e.g. pay-for-performance [P4P]) for maternal health and address structural determinants of women’s health by creating favourable conditions to improve the status of women and foster their overall socioeconomic well-being.
Research on Early Warning of Renal Damage in Hypertensive Patients Based on Stacking Strategy
Authors: Bi Qiubo , Kuang Zemin , E Haihong , Song Meina , Tang Xinying , Liu Xing
Published: August 2020

Background: Among the problems caused by hypertension, the early renal damage is often ignored. It can not be diagnosed until the condition is serious and irreversible damage occurs. So we decide to screen and explore related risk factors for hypertensive patients with early renal damage, and establish early-warning model of renal damage based on the data-mining method to achieve early diagnosis for hypertensive patients with renal damage. Methods: With the aid of electronic information management system for hypertensive specialist out-patient, we collected 513 cases of original untreated hypertensive patients, and recorded their demographic data, ambulatory blood pressure parameters, blood routine index and blood biochemical index to establish the clinical database, then we screen risk factors for early renal damage through feature engineering, and use Random Forest, Extra-Trees and XGBoost to build a early-warning model respectively. Finally, we build a new model by model fusion based on Stacking strategy. We use cross validation to evaluate the stability and reliability of each mode to determine the best risk assessment model. Results: According to the degree of importance, the descending order of features selected by feature engineering is the drop rate of systolic blood pressure at night, the red blood cell distribution width, blood pressure circadian rhythm, the average diastolic blood pressure at daytime, body surface area, smoking, age and HDL. Among the early-warning models of renal damage without model fusion, XGBoost has the best effect, the average accuracy of 5-fold cross validation is 0.90457. And the average accuracy of the two-dimensional fusion model based on Stacking strategy is 0.91428, which is greatly improved. Conclusions: Through feature engineering and risk factor analysis, we select the drop rate of systolic blood pressure at night, the red blood cell distribution width, blood pressure circadian rhythm and the average diastolic blood pressure at daytime as early-warning factors of early renal damage in patients with hypertension. On this basis, the two-dimensional fusion model based on Stacking strategy has a better effect than the single model, which can be used for risk assessment of early renal damage in hypertensive patients.
Human Nuclear Receptors (NRs) Genes have Prognostic Significance in Hepatocellular Carcinoma Patients
Authors: Sun Guangtao , Sun Kejian , Shen Chao
Published: August 2020

Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality in the world. Human nuclear receptors (NRs) have been identified to closely related to various cancer. However, the prognostic significance of NRs on HCC patients has not been studied in detail.Method: We downloaded the mRNA profiles and clinical information of 371 HCC patients from TCGA database and analyzed the expression of 48 NRs. The consensus clustering analysis with the mRNA levels of 48 NRs was performed by the "ConsensusClusterPlus". The Univariate cox regression analysis was performed to predict the prognostic significance of NRs on HCC. The risk score was calculated by the prognostic model constructed based on eight optimal NRs which were selected. Then Multivariate Cox regression analysis was performed to determine whether the risk score is an independent prognostic signature. Finally, the nomogram based on multiple independent prognostic factors including risk score and TNM Stage was used to predict the long-term survival of HCC patients.Results: NRs could effectively separate HCC samples with different prognosis. The prognostic model constructed based on the eight optimal NRs (NR1H3, ESR1, NR1I2, NR2C1, NR6A1, PPARD, PPARG and VDR) could effectively predict the prognosis of HCC patients as an independent prognostic signature. Moreover, the nomogram was constructed based on multiple independent prognostic factors including risk score and TNM Stage and could better predict the long-term survival for 3- and 5-year of HCC patients.Conclusion: Our results provided novel evidences that NRs could act as the potential prognostic signatures for HCC patients.
Electronic Data Management in Public Health and Humanitarian Crises. Upgrades, Scalability and Impact of ODK
Authors: Marks Michael , Lal Sham , Brindle Hannah , Gsell Pierre-Stéphane , MacGregor Matthew , Stott Callum , Rijdt Martijn van de , Almazor Guillermo Gutiérrez , Golia Suman , Watson Conall , Diallo Abdourahamane , Toure Alhassane , Houlihan Catherine , Keating Patrick , Martin Hélène , Restrepo Ana-Maria Henao , Anokwa Yaw , Roberts Chrissy
Published: August 2020

BackgroundODK provides software and standards that are popular solutions for off-grid electronic data collection and are the basis of related products like CommCare, Enketo, Ona, SurveyCTO and KoBoToolbox. In combination with the use of statistical analysis software such as R, these tools provide fully open-source options for off-grid use in public health data collection, management, analysis and reporting.ResultsNew functions were developed to facilitate the use of ODK, Enketo and R in large scale data collection, aggregation, monitoring and near-real-time analysis during clinical research in health emergencies. We present open-source enhancements to ODK that include a built-in audit-trail, a framework and companion app for biometric registration of ISO/IEC 19794-2 fingerprint templates, enhanced performance features, better scalability for studies featuring millions of data form submissions, increased options for parallelisation of research projects, and pipelines for automated management and analysis of data. We also developed novel encryption protocols for enhanced web-form security in Enketo. During the 2018-2020 Ebola epidemic in the North Kivu & Ituri regions of Democratic Republic of Congo, ODK, Enketo and R were leveraged to support the DRC Ministère de la Santé RDC and World Health Organization in their efforts to administer an experimental vaccine (VSV-Zebov-GP) as part of their strategy to control the transmission of infection. Against the backdrop of a complex and challenging epidemic response, our enhanced platform of open tools was used to collect and manage data from more than 280,000 eligible study participants who received VSV under informed consent. These data were used to determine whether the VSV-Zebov-GP was safe and effective and to guide daily field operations.ConclusionsWe present open source developments that make electronic data management during clinical research and health emergencies more viable and robust. These developments will also enhance and expand the functionality of a diverse range of data collection platforms (Ona, KoBoToolbox etc.) that are based on the ODK software and standards.FundingThis research is funded by the Department of Health and Social Care using UK Aid funding and is managed by the NIHR (PR-OD-1017-20001).
The optimal anesthesia mothod for external cephalic version (ECV): a randomized controlled trial
Authors: Yu Wei , Wang Xiaofeng , Wang Yilong , Li Haibing , Meng Qiong , yang zeyong
Published: August 2020

Background: The aim of the study is to investigate the success rate of ECV and relevant complications with intrathecal analgesia for singleton breech pregnancy.Methods: Sixty pregnant women received obstetrical regular prenatal care were randomly divided into EA group( epidural anesthesia, n = 30), CSEA group( combined spinal-epidural anesthesia, n = 30), control group(no analgesia, n = 30). The primary outcome of our study was the success rate of ECV confirmed by ultrasound. Visual analogue scale,, the rate of cesarean section and relevant side effect were recorded.Results: The success rate of spontaneous inversion to cephalic version was 76.7% in EA group, which was higher than that in CSEA group (53.3%) and control group (46.7%) (p = 0.058 and p = 0.017, respectively). The rate of cesarean section in EA group was 33.3%, which was also lower than that in CSEA group (53.3%) and control group (50.0%), however, the difference was not statistically significant between CSEA group and EA group(p = 0. 19). The VAS scores in the EA group and the spinal group were respectively 1.87 ± 2.94 and 1.73 ± 2.71 ,obviously better than that of the control group (6.84 ± 3.08) (p = 0.001 and p = 0.001).It was no significant difference between EA group and Control group ( p = 0. 118). The incidence of hypotension, nausea and vomiting, and fetal heart rate deceleration in CSEA group was significantly higher than that in control group (p = 0.000, p = 0.161, p = 0.129). The occurrence rate of spontaneous fetal heart rate deceleration in the EA, CSEA and control group were 6.7%, 20% and 6.7%, respectively, the differences were not statistically significant.Conclusions: EA can be more effective to enhance the success rate of spontaneous inversion to cephalic version than CSEA, and CSEA is accompanied with more side effects. Meanwhile, EA or CSEA don’t affect the rate of cesarean section of ECV for breech single pregnancy. (Registration number: ChiCTR1800017124)Trial registration: Name of the registry: Comparison of epidural analgesia with dexmedetomidine or sufentanil combined with ropivacaine: an observational study of multi-center ; Trial registration number: ChiCTR1800017124; Date of registration: 07-13-2018; URL of trial registry record: http://www.chictr.org.cn/edit.aspx?pid=29087&htm=4
MiR-199a-5p-HIF-1α-STAT3 positive feed-back loop contributes to the progression of NSCLC
Authors: Yang Xingping , Zheng Yuzhen , Tan Jian , Hu Xiansheng , Tian Renjiang , Shen Piao , Liao Hongying
Published: August 2020

Background

Non-small cell lung cancer (NSCLC), is the most common malignancy worldwide. MiR-199a-5p has been reported to play important roles in multiple tumors, inclusive of NSCLC. Whereas, little is definitively known pertaining to its explicit mechanism of action in NSCLC.
Methods

Expression of miR-199a-5p and HIF-1α mRNA were quantified employing qRT-PCR. H1299 and A549 cells were transiently transfected with miR-199a-5p mimics or inhibitors. Then CCK-8 assays, flow cytometry analysis, Transwell assay were implemented for detecting cell proliferation, cell cycle, apoptosis, migration and invasion of NSCLC cells, respectively. HIF-1α, STAT3 and p-STAT3 expression were detected via Western blotting. Bioinformatic analysis and dual-luciferase assay were performed for monitoring interaction between miR-199a-5p, HIF-1α and STAT3. Xenograft models were established with nude mice for further analyzing Bevacizumab resistance of NSCLC.
Results

MiR-199a-5p expression was markedly attenuated in NSCLC tissues and cell lines. Overexpression of miR-199a-5p constrained proliferation, migration, invasion but induced apoptosis of NSCLC cells. HIF-1α was identified as a direct target of miR-199a-5p. Further study confirmed a positive feed-back loop between miR-199a-5p, HIF-1α and STAT3. Co-transfection of HIF-1α or STAT3 overexpression plasmids counteracted effects of miR-199a-5p. Further study substantiated that feed-back loop might be in association with the Bevacizumab resistance of NSCLC cells .
Conclusion

MiR-199a-5p constrained the progression and Bevacizumab resistance of NSCLC by suppressing HIF-1α and STAT3, while HIF-1α/STAT3 axis suppressed the expression of miR-199a-5p, which forms a positive feed-back loop to promote the sustaining progression of NSCLC.
Clinical Outcomes Observation in Stage IIB–III Cervical Cancer Treated by Adjuvant Surgery Following Concurrent Chemoradiotherapy
Authors: Li Yong , Chen Zhiying , Wang Xiang , Li Xiumei , Zhou Jie , Zhang Yongchun
Published: August 2020

Objective: To explore the feasibility of adjuvant surgery following concurrent chemoradiation therapy (CCRT) in stage ⅡB–Ⅲ cervical cancer. And analyze risk factors of recurrence after surgery. Methods: Forty-nine patients diagnosed with stage ⅡB–Ⅲ cervical cancer were reviewed retrospectively. Investigated the risk factors of recurrence after surgery using Chi-squared Test and further analyzed multiple factors affecting postoperative recurrence using the multi-factor logistic regression. Furthermore, the correlation of surgery outcomes (including operation time, bleeding, and hospitalization date and surgery complications) with the time which carried out between CCRT and completion surgery was analyzed. Results: Tumor histology and residual tumor in the cervix were significantly associated with postoperative recurrence (P = 0.014 and P = 0.040, respectively). Logistic regression analysis demonstrated that the independent risk factors of postoperative recurrence were age and residual tumor in the cervix (P = 0.017 and P = 0.030, respectively). Compared with completion surgery was carried out ≤ 6 weeks after CCRT, the operation time, bleeding, hospitalization date and surgery complications were more than > 6 weeks group. Moreover, bleeding and surgery complications were statistically significant (P = 0.019 and P = 0.044, respectively).Conclusion: CCRT combined surgery for stage ⅡB–Ⅲ cervical cancer was feasible, reduced the rate of postoperative recurrence and surgery complications were tolerated. CCRT combined surgery might improve the local control of lesion.
Association between Premature Ovarian Insufficiency and Gut Microbiota
Authors: Wu Jiaman , Zhuo Yuanyuan , Liu Yulei , Chen Yan , Ning Yan , Yao Jilong
Published: August 2020

Premature ovarian insufficiency (POI) is characterized by impairment of ovarian function on a continuum before the age of 40 years. POI is affected by multiple factors. Considering new insights from recent gut microbiome studies, this study aimed to investigate the relationship between gut microbial community structure and POI. Subjects were recruited at the Shenzhen Maternity&Child Healthcare Hospital. Fecal microbial community profiles of healthy women (n = 18), women with POI (n = 35) were analyzed using 16S rRNA gene sequencing based on Illumina NovaSeq platform. Compared to the controls, the serum levels of FSH, LH, T and FSH/LH ratio significantly increased in women with POI, whereas E2 and AMH decreased significantly. Higher weighted UniFrac value was observed in POI women compared with healthy women. Phylum Firmicutes, genera Bulleidia and Faecalibacterium were more abundant in healthy women, while phylum Bacteroidetes, genera Butyricimonas, Dorea, Lachnobacterium and Sutterella enriched significantly in women with POI. Moreover, these alterations of the gut microbiome in women with POI was closely related to FSH, LH, E2, AMH level and FSH/LH ratio. Women with POI had altered microbial profiles in their gut microbiome, which were associated with serum hormones levels. These results will shed a new light on the pathogenesis and treatment for POI.
InterTADs: Integration of Multi-Omics Data on Topological Associated Domains
Authors: Tsagiopoulou Maria , Pechlivanis Nikolaos , Psomopoulos Fotis
Published: August 2020

Background: The integration of multi-omics data can greatly facilitate the advancement of research in Life Sciences by providing new insights on how biological systems interact. However, there is currently no widespread procedure for a robust, efficient and meaningful multi-omics data integration; the approach presented here is a first attempt towards increasing the reliability of data discovery power compared to the processing of individual biodata sets. Results: Here, we proposed a high-speed framework, called InterTADs, for integrating multi-omics data from the same physical source (e.g. patient) taking into account the chromatin configuration of the genome, i.e. the topologically associating domains (TADs). The main concept of the proposed methodology is to create a single matrix with all different events (e.g. DNA methylation, expression, mutation) combined with their genome coordinates and the respective quantitative metrics after application of the appropriate scaling. The events are divided into their related TADs according to the chromosomal location and each TAD is evaluated for statistically significant differences between the groups of interest (e.g. normal cells vs cancer cells). Finally, several visualization approaches are available, including the mapping of the events on the chromosomal location of the TAD as well as the distribution of the counts within a given TAD across the different study groups.Conclusions: InterTADs provides a general framework for integrating multi omics data and relating them with the TADs. This could lead to the extraction of new biological insight of the examined case study. InterTADs is an open-source tool implemented in R and licensed under the MIT License. The source code is freely available from https://github.com/nikopech/InterTADs.
The PHD Transcription Factor Cti6 is Involved in the Fungal Colonization and Aflatioxin B1 Biological Synthesis of Aspergillus Flavus
Authors: Zhang Mengjuan , Lin Guanglan , Pan Xiaohua , Song Weitao , Tan Can , Chen Xuan , Yang Yanling , Zhuang Zhenhong
Published: August 2020

Aspergillus flavus and its main secondary metabolite AFB1 pose a serious threat to several important crops worldwide. Recently, it has been reported that some PHD family transcription factors are involved in the morphogenesis and AFB1 biological synthesis in A. flavus, but the role of Cti6, a PHD domain containing protein in A. flavus, is totally unknown. The study was designed to reveal the biological function of Cti6 in the fungus by deletion of cti6, and its two domains (PHD and Atrophin-1) through homologous recombination, respectively. The results showed that Cti6 might up-regulate the mycelium growth, conidiation, sclerotia formation and AFB1 biological synthesis of A. flavus by its PHD domain, while Atrophin-1 also improved the conidiation of the fungus. The qRT-PCR analysis showed that Cti6 increased the conidiation of the fungus through AbaA and BrlA mediated conidiation pathway, triggered the formation of sclerotia by orthodox sclerotia formation pathway, and improved the production of AFB1 by orthodox AFB1 synthesis pathway. Crops models analysis showed that A. flavus Cti6 plays vital role in colonization and the production of AFB1 on the host grains mainly via PHD domain. Bioinformatics analysis showed Cti6 is conservative in Aspergillus spp., and mCherry mediated subcellular localization showed that most Cti6 accumulated in the nuclei, which reflected that Cti6 performed its important biological function in the nuclei in Aspergillus spp.. The results of the current study elucidate the roles of PHD domain containing proteins in the mechanism of the infection of crops by A. flavus, and provided a novel target for effectively controlling the contamination of Aspergillus spp. to crops.
HPV E6 Protein Associated SOX21-AS1 Promotes YAP/TAZ Activation by Attenuating YAP1 Ubiquitination in Human Cervical Cancer
Authors: Liu Qin , Zhu Zhiwei , Lian Senlin , Zhu Lixia , Pan Jiahui , Xu Song , Zhang Xuegang , Zhang Juping , Xu Huizi , Chen Yun , Wang Guoqing , Runqiu Jiang
Published: August 2020

Background: The human papillomavirus (HPV), especially HPV 16 type infection, is one of the well-known causes for human cervical cancer, we sought to investigate HPV 16 regulating lncRNA and its role in cervical carcinogenesis. Methods: The potential HPV16 related lncRNAs were screened by using bioinfomatic analysis. The relationship between SOX21-AS1 and clinical features was studied by using clinical samples. Its oncogenic roles were explored in vitro. Results: A HPV 16 infection-specific lncRNA, SOX21-AS1 was spotted by screening the Cancer Genome Atlas TCGA database, and its expression was seriously related to Hippo signaling pathway by using Gene Set Enrichment Analysis. Total 40 cases patients suffered from cervical carcinomas (CCs) were involved, we found that SOX21-AS1 was over-expressed in those CCs patients who were positive for HPV 16 infection compared to those who were negative. We also found that SOX21-AS1 expression was positively related to E6 protein but not E7 expression, which is a carcinogenic protein of HPV 16. Also, YAP1/TAZ/TEAD complex can increase SOX21-AS1 transcription by binding to its promoter region. SOX21-AS1 can promote cell proliferation and invasion in CCs cell lines in a YAP1 activation-dependent manner. We found that SOX21-AS1 can promote YAP1 activation by preventing YAP1 phosphorylation at s127 residue and further preventing its degradation by binding to 14-3-3. Conclusion: In conclusion, SOX21-AS1 is an HPV16 specific lncRNA which can promote tumor growth and metastasis by targeting the Hippo signaling pathway.
Immunomodulatory drug and dexamethasone-containing triple versus doublet combination treatments for relapsed or refractory multiple myeloma: a meta-analysis of phase III randomized controlled trials
Authors: Gao Minjie , Yan Xiao , Li Fei , Xu Kaihong , Mu Qitian , Sheng Lixia , Wang Yi , Tompkins Van S. , Ouyang Guifang
Published: August 2020

Background

Triplet therapy has become the standard of care for relapsed or refractory multiple myeloma (RRMM) over the past few years. Prior to that, doublet therapy including dexamethasone and an immunomodulatory were standard. Several systematic studies have been conducted and many combinations with variable triplet therapies but have not always used the former standard therapy as a benchmark. The objective of this meta-analysis was to evaluate the efficacy and safety of triplet combinations that included dexamethasone and an immunomodulatory drug versus a doublet combination of just dexamethasone and an immunomodulatory for the treatment of RRMM.
Methods

A comprehensive literature search (PubMed, EMBASE, Cochrane Library) for phase III randomized controlled trials for efficacy and safety of triplet versus doublet combinations that specifically included dexamethasone and an immunomodulatory drug for treatment of RRMM. Efficacy (ORR, PFS, OS) and adverse events (≥ grade 3) were assessed using traditional statistical measures for aggregate data.
Results

Of 235 potential reports, 6 met the inclusion criteria (N = 115–792 participants). The methodological quality was ≥ 4 Jadad score for each. Triplet treatment had higher ORR (HR = 0.74, 95%CI: 0.65–0.84, P ≤ 0.001), PFS (HR = 0.63, 95%CI: 0.52–0.75, P ≤ 0.001), and OS (HR = 0.74, 95%CI: 0.65–0.84, P ≤ 0.001). The incidence of ≥ grade 3 diarrhea and fatigue were significantly higher in the triplet combination group. There was a trend toward increased incidence of ≥ grade 3 neutropenia, thrombocytopenia, thromboembolism, and peripheral neuropathy in the triplet therapy group. Notably, triplet therapy had a significantly lower rate of anemia compared to doublet therapy.
Conclusions

This study reinforces current guidelines and recommendations for triplet combinations containing dexamethasone and an immunomodulatory drug.