bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association Between an Increase in Blood Urea Nitrogen at 24 Hours and Worse Outcomes in COVID-19 Pneumonia
Authors: Ye Bo , Deng Hongbin , Tong Zhihui , Liang Jingjing , Zhou Jing , Li Gang , Mao Wenjian , Zhao Hanwei , Ke Lu , Li Weiqin 
Published: September 2020

Abstract
Background and objectives: The dynamic change of blood urea nitrogen (BUN) have been proved to be related to the worse outcomes in various diseases such as pulmonary embolism, acute pancreatitis and acute nonvariceal upper GI bleeding. In the present study, we aimed to identify the association between blood urea nitrogen (BUN) change and clinical outcomes in patients presenting with COVID-19 pneumonia.Methods: This is a retrospective study conducted in the Huoshenshan hospital. Patients with laboratory-confirmed COVID-19 from Feb 5th to March 5th in 2020 who had BUN level tested on admission and on the second day consecutively were included. Patients were stratified into two groups according to the BUN change (increase vs. no increase) during the first 24 hours. The primary outcome was in-hospital mortality. Moreover, other clinical outcomes were also compared. The potential risk factors of in-hospital mortality were analyzed. Results: There were 266 patients included in the study. The mean change in BUN at 24 hours was 1.0 mg/dL, with 206 patients (77.4%) experiencing no increase in BUN and 60 patients (22.6%) experiencing an increase in BUN. In-hospital mortality was significantly higher in the BUN increase group compared to no increase group (30.0% vs. 5.8%, P<0.001). BUN increase group also had higher requirement for ICU admission, use of invasive mechanical ventilation and incidence of AKI (all P<0.001). After adjusted for related factors, the BUN increase was independently associated with the mortality with an odds ratio of 7.427[95% CI 2.370-23.279]. In the multivariable and survival analysis, BUN increase was also found to be associated with survival regardless of the admission BUN.Conclusions: In patients with COVID-19, BUN increase at 24 hours was an independent predictor for a composite clinical outcome and in-hospital mortality. The association of BUN increase with worse outcomes further emphasizes the importance of monitoring BUN change and kidney function in the course of COVID-19.
Machine learning prediction models based on hub genes related to immune phenotypes in muscle-invasive bladder cancer treated with immune checkpoint blockade
Authors: Li Peiheng , Chen Zhi-Xin , Wang Dong , Zheng Zhi , Ji Zhi-Gang 
Published: September 2020

Abstract
Background

Bladder cancer is one of the most frequent cancer in the world. Muscle-invasive bladder cancer (MIBC) is a more aggressive subtype with higher morbidity and mortality. ICB therapy has shown potential for treating MIBC, but is limited due to the lack of predictive biomarkers.
Methods

1601 MIBC transcriptomic profiles were obtained from 10 datasets. Unsupervised clustering of immune phenotypes in MIBC were performed based on immune-related signature genes. We analyzed the characteristics including immune microenvironments, metabolic pathways, and survival rates in different phenotypes. Multi-omic analysis and WGCNA were performed to identify hub genes distinguishing phenotypes related to prognosis. A model was established and CART was employed to predict the response of patients treated with ICB.
Results

Of various immune phenotypes, cluster 3C was the most “inflamed” subcluster with the best prognosis, while cluster 1A was associated with “non-inflammation” and worse prognosis. WGCNA analysis identified 5 hub genes related to the survival rate of patients, IFNG, CXCR6, IL2RB, LCK, and PSMB10, which were utilized for prognostic score model and decision tree analysis. The areas under the curve (AUC) of the ROC curves predicting 5-year endpoint generated from the risk-based prediction model were 0.652. The mean accuracy, sensitivity, and specificity of CART for predicting stable disease/progressive disease were 70.1%, 70.0% and 71.7%.
Conclusions

The 5 hub genes and generated models showed the potential for predicting the prognosis for patients receiving ICB therapy. The molecular mechanisms regulating the expression of the hub genes require further studies in the future.
REMOTE#RESEARCH - A Telediagnosis Assistance System for Multiple-Lead Electrocardiography
Authors: Bentes Paulo , Nadal Jurandir 
Published: September 2020

Abstract
Background : The diffusion of telemedicine opens up a new perspective for the development of technologies furthered by Biomedical Engineering. In particular, herein we deal with those related to telediagnosis through multiple-lead electrocardiographic signals. Objectives : This study focuses on the proof-of-concept of an internet-based telemedicine system as a use case that attests to the feasibility for the development, within the university environment, of techniques for remote processing of biomedical signals for adjustable detection of myocardial ischemia episodes. Methods : At each signal lead, QRS complexes are detected and delimited with the J -point marking. The same procedure to detect the complex is used to identify the respective T wave, then the area over the ST segment is applied to detect ischemia-related elevations. The entire system is designed on web-based telemedicine services using multiuser, remote access technologies, and database.Results : The measurements for sensitivity and precision had their respective averages calculated at 11.79% and 24.21% for the lead s of lower noise. T he evaluations regarding the aspects of user friendliness and the usefulness of the application, resulted in 88.57% and 89.28% of broad or total acceptance, respectively .Conclusions : They are robust enough to enable scalability and can be offered by cloud computing, besides enabling the development of new biomedical signal processing techniques within the concept of distance services, using a modular architecture with collaborative bias.
Predicting Language Recovery in Post-Stroke Aphasia using Behavior and Functional MRI
Authors: Iorga Michael , Higgins James , Caplan David , Zinbarg Richard , Kiran Swathi , Thompson Cynthia K. , Rapp Brenda , Parrish Todd B. 
Published: September 2020

Abstract
Background: Language outcomes after speech and language therapy in post-stroke aphasia are challenging to predict. This study examines behavioral language measures and resting state fMRI (rsfMRI) as prognostics for response to language therapy. Methods: Seventy patients with chronic aphasia were recruited and treated for one of three deficits: anomia, agrammatism, or dysgraphia. Treatment effect was measured by performance on a treatment-specific language measure, assessed before and after three months of language therapy. Each patient also underwent an additional 27 language assessments and an fMRI scan at baseline. Patient scans were decomposed into 20 components by group independent component analysis, and each component time series was summarized by its fractional amplitude of low-frequency fluctuations (fALFF). Results: Treatment effects were modelled with elastic net regression, using clinical language measures and fALFF imaging predictors independently. Correlation analyses showed high performance for language measures in anomia (r = 0.958, n = 30) and for fALFF predictors in agrammatism (r = 0.940, n = 11) and dysgraphia (r = 0.925, n = 18). These models are state-of-the-art for aphasia recovery prediction. Conclusion: Predicting aphasia recovery with rsfMRI features may outperform predictions from clinical language measures in some patient populations. This suggests rsfMRI may have prognostic value for chronic aphasia patients undergoing language therapy. Differentiating patients who respond to therapy from those who do not is a first step towards personalized treatment in post-stroke aphasia.
Immune Score Closely Associated With Tumor Microenvironment as A Prognostic Factor in Lung Adenocarcinoma
Authors: Li Na , Chen Xiaoling , Liu Chang , Feng Yong , Sun Xiaoqiang , Liu Yongyu 
Published: September 2020

Abstract
Background: The tumor microenvironment plays a vital role in tumor biology and has recently attracted widespread attention. However, the prognostic significance of integrated immune scores in lung adenocarcinoma has not yet been identified. This study aimed to systematically estimate the association between immune scores and prognosis and develop a clinical nomogram to predict the survival of patients with lung adenocarcinoma. This study also systematically explored the underlying prognostic factors of the immune score in lung adenocarcinoma.Methods: Public datasets for lung adenocarcinoma was acquired from The Cancer Genome Atlas data portal. The immune score of each sample was calculated using the ESTIMATE algorithm. Univariate and multivariate Cox regression analyses identified several significant prognostic factors and further developed a prognostic nomogram. The C-index, calibration curve, and ROC curve were used to evaluate the predictive accuracy and discriminative ability of the resultant nomogram. Results: We found that patients with higher immune scores had a better prognosis (log rank test p = 0.0004). The nomogram that integrated the immune score could effectively stratify high-risk LUAD patients in terms of clinical response. Patients in the high-risk groups usually had a worse prognosis (log rank test p < 0.0001) and higher mortality. The mortality rate in high and low risk groups was 42.67% and 26.37%, respectively (p < 0.0001). In addition, correlation analysis showed that the immune score was significantly dependent on the mRNA expression of immunotherapy-associated biomarkers (PD-1, PD-L1, and LAG3) as well as on the presence of certain immune cell subtypes, but had no correlation with tumor mutation burden.Conclusion: The immune score is a prognostic factor in lung adenocarcinoma. The nomogram with an integrated immune score can effectively predict the survival of patients with lung adenocarcinoma. The mechanism by which the immune score estimates the prognosis of patients with lung adenocarcinoma is related to the tumor immune microenvironment.
Genome-wide transcriptomic analysis of n-caproic acid production in Ruminococcaceae bacterium CPB6 with lactate supplementation
Authors: Tao Yong , Lu Shaowen , Wang Yi , Wei Cuicui , Jin Hong , He Xiaohong 
Published: September 2020

Abstract
Background

n-Caproic acid (CA) is gaining increased attention due to its high value as a chemical feedstock. Ruminococcaceae bacterium strain CPB6 is an anaerobic mesophilic bacterium that is highly prolific in its ability to perform chain elongation of lactate to CA. However, little is known about the genome-wide transcriptional analysis of strain CPB6 for CA production triggered by the supplementation of exogenous lactate.
Results

In this study, 0.5% lactate was supplemented into the fermentation with Ruminococcaceae bacterium CPB6 for CA production. Compared to the control (without lactate supplementation), lactate supplementation led to earlier CA production and higher final CA titer and productivity. Transcriptional analysis was carried out using RNA-Seq for the culture with and without lactate supplementation (two groups) at growth and stationary phases, respectively. It has been indicated that 295 genes whose changes in expression patterns were substrate and/or growth dependent. These genes cover crucial functional categories. Specifically, 5 genes responsible for the reverse β-oxidation pathway, 11 genes encoding ATP-binding cassette (ABC) transporters, 6 genes encoding substrate-binding protein (SBP) and 4 genes encoding phosphotransferase system (PTS) transporters were strikingly upregulated in response to the addition of lactate. These genes would be candidates for future studies aiming at understanding the regulatory mechanism of lactate conversion into CA, as well as for the improvement of CA production in strain CPB6.
Conclusions

This study suggested that lactate supplementation can promote CA production by altering the expression patterns of genes involved in the essential metabolic pathways, such as central pyruvate metabolism, the reverse β-oxidation pathway, ABC and PTS transports. The findings presented herein reveal unique insights into the biomolecular effects of lactate on CA production at the gene transcriptional level.
Protocol to Evaluate the Implementation of an Enterprise-Wide Initiative to Increase Access to Lung Cancer Screening in the Veterans Health Administration
Authors: Lewis Jennifer A. , Spalluto Lucy B. , Henschke Claudia I. , Yankelevitz David F. , Aguayo Samuel M. , Morales Providencia , Avila Rick , Audet Carolyn M. , Prusaczyk Beth , Lindsell Christopher J. , Callaway-Lane Carol , Dittus Robert S. , Vogus Timothy J. , Massion Pierre P. , Limper Heather M. , Kripalani Sunil , Moghanaki Drew , Roumie Christianne L. 
Published: September 2020

Abstract
Background

The Veterans Affairs Partnership to increase Access to Lung Screening (VA-PALS) is an enterprise-wide initiative to implement high quality lung cancer screening programs at VA medical centers (VAMCs). VA-PALS will be using implementation strategies that include program navigators to coordinate screening activities, trainings for navigators and radiologists, an open-source software management system, tools to standardize low-dose computed tomography (LDCT) image quality, and access to a support network. Individual VAMCs can utilize strategies according to their local contextual factors. In this protocol, we describe the planned program evaluation for the initial 10 VAMCs participating in VA-PALS.
Methods

The implementation of programs will be evaluated using the Consolidated Framework for Implementation Research to ensure broad contextual guidance. Program evaluation measures have been developed using the Reach, Effectiveness, Adoption, Implementation and Maintenance framework. Adaptations of screening processes will be assessed every six months using the Framework for Reporting Adaptations and Modifications to Evidence Based Interventions. Measures collected will reflect the inner setting at each VAMC, estimate and describe the population reached, adoption by providers, implementation of the programs, report patient clinical outcomes and maintenance of screening programs. Analyses will primarily use descriptive statistics with means, medians, and frequencies. Outcomes will be compared over time and among VA-PALS VAMCs and non-VA-PALS VAMCs in interrupted time series analyses. Assessment of contextual factors and the relationship between predictors, such as organizational readiness and improved implementation, will be evaluated. Adaptations of processes to overcome barriers will be identified and evaluated for association with implementation.
Conclusion

This theory-based protocol will evaluate the implementation of lung cancer screening programs across the Veterans Health Administration (VHA) using scientific frameworks. The findings will inform plans to expand the VA-PALS initiative beyond the original sites and can guide implementation of lung cancer screening programs more broadly within and outside VHA.
Combination of Monocyte Human Leukocyte Antigen-DR and β-d-Glucan for the Early Diagnosis of Invasive Candida Infection in Critically Ill Patients: A Proof of Concept Study
Authors: Jung Boris , Bihan Clément Le , Portales Pierre , Bourgeois Nathalie , Vincent Thierry , Lachaud Laurence , Chanques Gerald , Conseil Matthieu , Corne Philippe , Massanet Pablo , Timsit Jean François , Jaber Samir 
Published: September 2020

Abstract
Background: Precision medicine risk stratification is desperately needed to both avoid systemic antifungals treatment delay and over prescription in the critically ill with risk factors. The aim of the present study was to explore the combination of host immunoparalysis biomarker (monocyte human leukocyte antigen-DR expression (mHLA-DR)) and Candida sp wall biomarker β-d-glucan in risk stratifying patients for secondary invasive Candida infection (ICI). Methods: Prospective observational study. Two intensive care units (ICU). All consecutive non-immunocompromised septic shock patients. Serial blood samples (n=286) were collected at day 0, 2 and 7 and mHLA-DR and β-d-glucan were assayed. Secondary invasive Candida sp infection occurrence were then followed. Results: Fifty patients were included, 42 (84%) had a Candida score equal or greater than 3 and 10 patients developed a secondary invasive Candida sp infection. ICU admission mHLA-DR expression and β-d-glucan (BDG) failed to predict secondary invasive Candida sp infection. Time-dependent cause-specific hazard ratio of ICI was 6.56[1.24-34.61] for mHLA-DR < 5000 Ab/c and 5.25[0.47-58.9] for BDG > 350pg/mL. Predictive negative value of mHLA-DR > 5000 Ab/c and BDG > 350 pg/mL combination at day 7 was 81% [95%CI 70-92]. Conclusion: This proof of concept study suggests that mHLA-DR predicts ICI in high risk patients with septic shock. The added value of BDG and other fungal tests should be regarded according to the host immune function markers. Trial registration: ClinicalTrials.gov identifier: NCT03136081Take home message: Combination of monocytic HLA-DR expression and beta-D-glucan in patients hospitalized for septic shock failed to predict invasive candida infection but could be useful to rule out infection.
Apo A1 / Apo B Ratio and Acute Coronary Syndrome Among Peritoneal Dialysis Patients
Authors: Chen Tianlei , Yang Min 
Published: September 2020

Abstract
Background: Acute coronary syndrome (ACS) is prevalent in continuous ambulatory peritoneal dialysis (CAPD) patients. But the association between apoprotein profile and ACS is not well known. Therefore, we aimed to investigate the relationship between apoproteins and ACS in CAPD patients.Methods: Eighty-one CAPD patients were included in this retrospective study. The primary endpoint was ACS. Predictors were baseline apoprotein levels, particularly the ratio of apoprotein A1 (Apo A1) / apoprotein B (Apo B). Binary logistics regression was used to determine the relationship between Apo A1 / Apo B and ACS. Results: During follow-up, 34 (41.98%) CAPD patients experienced an ACS. ACS patients had higher levels of total cholesterol (p = 0.03), LDL-C (p = 0.04), CRP (p = 0.01), and Apo B (p < 0.01). However, hemoglobin (p = 0.01) and the Apo A1 / Apo B (p < 0.01) were lower in the ACS group than the non-ACS group. Patients with Apo A1 / Apo B ≥ 1.105 experienced fewer ACS compared with those with Apo A1 / Apo B < 1.105 (33.33% vs. 75.56%, p = 0.03). In binary logistics regression, Apo A1 / Apo B (OR, 0.01; 95% CI, 0.00-0.77; p = 0.04) was independently associated with ACS. Conclusions: Apo A1 / Apo B were strongly associated with ACS, and may be considered as a predictor of future ACS in CAPD patients.
Tanshinone IIA&nbsp;Combined With CsA&nbsp;Inhibit Myocardial Cell Apoptosis Induced by Renal Ischemia-reperfusion Injury by Modulating Mitochondrial Function Through PI3K/Akt/Bad Pathway in Obese Rats&nbsp;
Authors: Tai He , Jiang Xiao-lin , Li Yue , Kong Liang , Yao Si-cheng , Song Nan , Lv Mei-jun , Wu Jin , Yang Ping , Yang Guan-lin , Kuang Jin-song , Lan Zhi-ming , Jia Lian-qun 
Published: September 2020

Abstract
Background: Acute myocardial injury (AMI), which is induced by renal ischemia-reperfusion (IR), is a significant cause of acute kidney injury (AKI)-related associated death. Obesity increases the severity and frequency of AMI and AKI. Tanshinone IIA (TIIA) combined with cyclosporine A (CsA) pretreatment was used to alleviate myocardial cell apoptosis induced by renal IR, and to determine whether TIIA combined with CsA would attenuate myocardial cell apoptosis by modulating mitochondrial function through the PI3K/Akt/Bad pathway in obese rats. Methods: Male rates were fed a high fat diet for 8 weeks to generate obesity. AKI was induced by 30 min of kidney ischemia followed 24 h of reperfusion. Obese rats were given TIIA (10 mg/kg·d) for 2 weeks and CsA (5 mg/kg) 30 min before renal IR. Related indicators were examined.Results: TIIA combined with CsA alleviated the pathohistological injury and apoptosis induced by renal IR in myocardial cells. In addition, TIIA combined with CsA improved cardiac function and decreased the serum myocardial enzyme spectrum in obese rats after renal IR. At the same time, TIIA combined with CsA improved mitochondrial function. Abnormal function of mitochondria was supported by decreases in the respiration controlling rate (RCR), intracellular adenosine triphosphate (ATP), oxygen consumption rate, and mitochondrial membrane potential (MMP), and increases in mitochondrial reactive oxygen species (ROS), opening of the mitochondrial permeability transition pore (mPTP), mitochondrial DNA damage, and mitochondrial respiratory chain complex enzymes (Ⅰ, Ⅱ, Ⅲ, Ⅳ, and Ⅴ). The injury of mitochondrial dynamic function was assessed by a decrease in Drp1, and increases in Mfn1 and Mfn2, and mitochondrial biogenesis injury was assessed by decreases in PGC-1, NRF1, and TFam. TIIA combined with CsA can attenuate apoptosis through modulating mitochondrial function through the PI3K/Akt/Bad pathway in obese rats.Conclusion: We used isolated mitochondria from rat myocardial tissues to demonstrate that myocardial mitochondrial dysfunction occurred along with renal IR to induce myocardial cell apoptosis; obesity aggravated apoptosis. TIIA combined with CsA attenuated myocardial cell apoptosis by modulating mitochondrial function through the PI3K/Akt/Bad pathway in obese rats.
Development of A Vitamin-related Gene Signature to Predict the Immune Characteristics and Prognosis of Glioma
Authors: Zhang Qing , Liang Qingyu , Guan Gefei , Cheng Wen , Yang Lianhe , Wu Anhua 
Published: September 2020

Abstract
Background: Vitamins not only play a pivotal role in maintaining homeostasis of the body, but also have complex impacts on the occurrence and progression of tumors. However, the effects of vitamins on glioma and the underlying mechanism have not been fully elucidated. Methods: Vitamin -related genes were extracted from the Molecular Signature Database v7.1 (MSigDB). The overlapping overall survival (OS)-related genes in The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), and GSE16011 cohorts screened out by univariate COX regression analysis were utilized to construct a risk model based on the TCGA cohort via random survival forest analysis and multivariate COX regression analysis. The powerful prognostic predictive potential of the vitamin-related risk signature was verified by Kaplan–Meier survival analysis and receiver operating characteristic (ROC) analysis in the three datasets. The ssGSEA method of the GSVA package was used for functional enrichment and immune cell component analyses. ESTIMATE score analysis was used for auxiliary analysis of glioma immune characteristics. A nomogram was constructed and assessed based on the TCGA dataset.Results: The vitamin-related six-gene (POSTN, IRX5, EEF2, RAB27A, MDM2, and ENO1) risk signature constructed based on the TCGA dataset accurately predicted the outcomes of glioma patients and credibly distinguished between different levels and molecular subtypes of glioma in the TCGA, CGGA, and GSE16011 cohorts. Gliomas with high risk scores exhibited high immune scores, low tumor purity, and immunosuppressive features. The nomogram constructed by combining the vitamin-related risk signature and clinicopathological factors precisely predicted the 1-, 3-, and 5-year OS of glioma patients.Conclusions: Our study revealed that the vitamin-related six-gene risk signature, as an independent prognostic factor, could accurately distinguish the grade, molecular subtype, and immune characteristics of glioma.