bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dimethyl itaconate inhibits TNF-α induced NF-κB signaling pathway in human epithelial cells
Authors: Zhang Yalei , Deng Xiaobing , Liang Hao , Guo Annan , Li Kenan , Liu Hongbo , Zhang Qi , Lai Luhua 
Published: February 2020

Abstract
Background:
Dimethyl itaconate (DMI), a membrane-permeable derivative of itaconate, was found to moderate IL-17-IκBζ-induced skin pathology including psoriasis in mouse experiments . TNF-α induced NF-κB pathway, which controls a variety of immune and inflammatory responses, was also proven to play a crucial role as mediator in psoriasis. However, whether DMI interacts with the TNF-α induced NF-κB pathway remains unclear.
Results:
Here we show that DMI inhibits TNF-α induced NF-κB transcriptional activities in dose-dependent manner in several human cell lines using dual luciferase assay and blocks the NF-κB nuclear entry. Moreover, DMI potently inhibits IKKβ dependent phosphorylation and degradation of IκBα in TNF-α induced activation of NF-κB pathway. We also demonstrate that DMI covalently binds to cysteine residue in IKKβ, a key regulator in NF-κB pathway, to suppress IKKβ activation and inhibit the canonical NF-κB pathway.
Conclusion
Our study presents a new mechanism for DMI as an anti-inflammatory agent that may have therapeutic potentials in treating NF-κB related human inflammatory diseases. Our results also suggest that itaconate produced by endogenous IRG1 may regulate NF-κB at post translation modification level, and the IRG1-itaconate-NF-κB axis could be targeted as a novel strategy for the treatment of IRG1-NF-κB mediated diseases.
CareConekta: study protocol for a randomized controlled trial of a mobile health intervention to improve engagement in postpartum HIV care in South Africa
Authors: Clouse Kate , Phillips Tamsin K , Camlin Carol , Noholoza Sandisiwe , Mogoba Phepo , Naidoo Julian , Langford Richard , Weiss Martin , Seebregts Christopher J. , Myer Landon 
Published: February 2020

Abstract
Background: South Africa is home to the world’s largest antiretroviral therapy program but sustaining engagement along the HIV care continuum has proven challenging in the country and throughout the wider region. Population mobility is common in South Africa, but important research gaps exist describing this mobility and its impact on engagement in HIV care. Postpartum women and their infants in South Africa are known to be at high risk of dropping out of HIV care after delivery and are frequently mobile.
Methods: In 2017, we developed a beta version of a smartphone application (app) – CareConekta – that detects a user’s smartphone location to allow for prospective characterization of mobility. Now we will adapt and test CareConekta to conduct essential formative work on mobility and evaluate an intervention – the CareConekta app plus text notifications and phone calls and/or WhatsApp messages – to facilitate engagement in HIV care during times of mobility. During the three-year project period, our first objective is to evaluate the feasibility, acceptability, and initial efficacy of using CareConekta as an intervention to improve engagement in HIV care. Our second objective is to characterize mobility among South African women during the peripartum period and its impact on engagement in HIV care. We will enroll 200 eligible pregnant women living with HIV and receiving care at the Gugulethu Midwife Obstetric Unit in Cape Town, South Africa.
Discussion: This work will provide critical information about mobility during the peripartum period and the impact on engagement in HIV care. Simultaneously, we will pilot test an intervention to improve engagement with rigorously-assessed outcomes. If successful, CareConekta offers tremendous potential as a research and service tool that can be adapted and evaluated in multiple geographic regions, study contexts, and patient populations.
Trial registration: ClinicalTrials.gov NCT03836625; registered February 8, 2019.
Tracking Implementation Strategies in the Randomized Rollout of a Veterans Affairs National Opioid Risk Management Initiative
Authors: Rogal Shari S. , Chinman Matthew , Gellad Walid F , Mor Maria K , Zhang Hongwei , McCarthy Sharon A. , Mauro Genna T. , Hale Jennifer A. , Lewis Eleanor T. , Oliva Elizabeth , Trafton Jodie A. , Yakovchenko Vera , Gordon Adam J. , Hausmann Leslie R.M. 
Published: February 2020

Abstract
Background In 2018, the Department of Veterans Affairs (VA) issued Notice 2018-08 requiring facilities to complete ‘case reviews’ for Veterans identified in the Stratification Tool for Opioid Risk Mitigation (STORM) dashboard as high risk for adverse prescription opioid-related outcomes. Half of facilities were randomly assigned to a Notice version including additional oversight. We evaluated implementation strategies used, whether strategies differed by randomization arm, and which strategies were associated with case review completion rates. Methods Facility points of contact completed a survey assessing their facility’s use of 68 implementation strategies based on the Expert Recommendations for Implementing Change taxonomy. We collected respondent demographic information, facility-level characteristics, and case review completion rates (percentage of high-risk patients who received a case review). We used Kruskal-Wallis tests and negative binomial regression to assess strategy use and factors associated with case reviews. Results Contacts at 89 of 140 facilities completed the survey (64%) and reported using a median of 23 (IQR: 16-31) strategies. The median case review completion rate was 71% (IQR: 48%-95%). Neither the number or types of strategies nor completion rates differed by randomization arm. The most common strategies were: using the STORM dashboard (97%); working with local opinion leaders (80%); and recruiting local partners (80%). Characteristics associated with case review completion rates included respondents being < 35 years old (incidence rate ratio, IRR:1.35, 95%CI: 1.09-1.67) and having <5 years in their primary role (IRR:1.23; 95%CI: 1.01-1.51), and facilities having more prior academic detailing around pain and opioid safety (IRR:1.40, 95%CI: 1.12-1.75). Controlling for these characteristics, implementation strategies associated with higher completion rates included: 1) monitoring and adjusting practices (adjusted IRR, (AIRR): 1.40, 95%CI: 1.11-1.77), 2) identifying adaptations while maintaining core components (AIRR: 1.28, 95%CI: 1.03-1.60), 3) conducting initial training (AIRR: 1.16, 95%CI: 1.02-1.50), and 4) regularly sharing lessons learned (AIRR: 1.32, 95%CI: 1.09-1.59). Conclusions In this national evaluation of strategies used to implement case reviews of patients at high risk of opioid-related adverse events, point of contact age and tenure in current role, prior pain-related academic detailing at the facility, and four specific implementation strategies were associated with case review completion rates, while randomization to additional centralized oversight was not.
Is Primary Chemoradiation A Better Treatment? A Retrospective Study of Early Stage Node-positive Cervical Cancer.
Authors: Zhang Nan , Zheng Hong 
Published: February 2020

Abstract
Background.
Cervical cancer is the second most frequently diagnosed cancer and the third leading cause of cancer death for women in developing countries. Radical hysterectomy with bilateral pelvic lymph node dissection is usually preferred for patients of stage IB1-IIA2. Currently, image examinations have certain limitations in diagnose of lymph node metastasis and their detection accuracies are not satisfactory. Only the pathological examination after removal of the suspected metastatic lymph nodes during surgery can conclusively identify the presence of metastasis. If there is a positive result of lymphatic metastasis, there is no clear guideline whether to complete a radical surgery, or to only conduct a systematic lymphadenectomy, followed with adjuvant Concurrent Chemoradiotherapy (CCRT). This retrospective study aimed to compare the efficacy and safety of the two treatment modalities.
Methods.
49 stage IB1-IIA2 cervical cancer patients with lymphatic metastasis confirmed by systemic pelvic and para-aortic lymph node dissection from 2007 to 2018 were reviewed. The patients were treated with either primary chemoradiation or radical hysterectomy followed by adjuvant chemoradiation after lymphadenectomy. Survival states and adverse events of the two treatments were compared.
Results.
Median follow-up time was 45 (range 11-119 months) months. In non-radical surgery group, 1 patient (1/15, 6.7%) relapsed and died, while in radical surgery group, 7 patients (7/27, 25.9%) relapsed and 5 (5/27, 18.5%) died. Significant difference was found in the mean progression-free survival between the two groups, which was 69(95%CI 49.118-88.882) months in non-radical surgery group and 44(95%CI 35.857-52.143) months in radical surgery group (p＜0.01). There was significant difference in three-year progression-free survival(86%vs.71%, p＜0.01). Grade 3-4 toxicity was comparable between the two groups (26.7% vs. 25.9%, p=0.958).
Conclusion.
For stage IB1-IIA2 cervical cancer patients with positive lymph node, primary chemoradiation after pelvic and para-aortic lymphadenectomy seems to have better survival outcomes compared with radical hysterectomy by laparoscopy plus chemoradiation in the retrospective study with limited cases. Evidence from a randomized controlled study is in need to confirm the optimal treatment for early stage node-positive cervical cancer.
Intrinsic Patient Factors Predictive of Inpatient Rehabilitation Facility Discharge Following Primary Total Knee Arthroplasty: A Systematic Review and Meta-Analysis.
Authors: Sattler Larissa Nicole , Hing Wayne Anthony , Rathbone Evelyne , Vertullo Christopher John 
Published: February 2020

Abstract
Background Total Knee Arthroplasty (TKA) reduces pain and improves function in those suffering from severe osteoarthritis. A significant cost of TKA is post-acute care, however, current evidence suggests that discharge to an Inpatient Rehabilitation Facility (IRF) has inferior outcomes to home discharge, with no greater benefit in physical function. Only individual studies have investigated TKA patient characteristics predictive of discharge destination, therefore, the aim is to systematically review the literature and meta-analyse intrinsic patient factors predictive of IRF discharge. If predictive factors are known, then early discharge planning and intervention strategies could be implemented. Methods Databases PubMed, CINAHL, Embase, Cochrane, and Pedro were searched up to October 2019 for articles investigating pre-operative intrinsic patient factors predictive of IRF discharge. For assessing the methodological quality of included studies, the Quality In Prognosis Studies (QUIPS) tool was used. Statistical analysis and graphical reporting were conducted in R statistical software. To assess the effect of predictors of discharge destination, odds ratios with the corresponding 95%CI were extracted from the results of univariate and multivariable analyses. Results A total of 9 articles published between 2011 to 2018 with 218,151 TKA patients were included. Of the 13 intrinsic patient factors reported, 6 met the criteria for synthesised review: age, obesity, comorbidity, gender, SF-12/VR-12 survey, and smoking. Due to the heterogeneity of statistical analysis and reporting 2 variables could undergo meta-analysis, gender and smoking. Female gender increased the likelihood of IRF discharge by 1.78 (OR=1.78; 95%CI=1.43–2.20; I2=33.3%), however, the relationship between smoking status and discharge destination was less certain (OR=0.80; 95%CI=0.42–1.50; I2=68.5%). Conclusion Female gender was shown to be predictive of IRF discharge after total knee arthroplasty. There was also a trend for those of older age, increased comorbidity or the severely obese to have an increased likelihood of IRF discharge. This systematic review and meta-analysis suggests that the heterogeneity of existing literature is inadequate to develop a predictive model for intrinsic patient factors associated with IRF discharge. Further, high quality studies of prospective design on predictive factors are warranted, to enable early discharge planning and optimise resource consumption on post-acute care following TKA.
Temporal Dynamics of the Human Microbiome
Authors: Kenney Toby , Gao Junqiu , Gu Hong 
Published: February 2020

Abstract
Background There has been a lot of research about the role of the microbiome in various processes. The research has focused almost exclusively on the structure of the microbiome at a single time-point. There have been several studies that measure the microbiome from a particular environment over time. However, even in these studies, little has been done to study the temporal dynamics of the microbiome. In this paper, we begin to rectify this situation. We analyse a widely studied microbial data set that contains a time series of the microbiome from four body sites on two healthy individuals. We choose a data set based on healthy individuals because we are interested in the baseline temporal dynamics of the microbiome. Results For this analysis, we focus on the temporal dynamics of individual genera, ignoring the interactions. We use simple stochastic differential equation models to assess the following three questions. (1) Does the microbiome exhibit temporal continuity? (2) Does the microbiome have a stable state? (3) To better understand the temporal dynamics, how frequently should data be sampled in future studies? We find that a simple Ornstein-Uhlenbeck model which incorporates both temporal continuity and reversion to a stable state fits the data for all genera better than a Brownian motion model that contains only temporal continuity. The Ornstein-Uhlenbeck model also fits the data better than modelling separate time points as independent. Under the Ornstein-Uhlenbeck model, we calculate the variance of the estimated mean reversion rate (the speed with which each genus returns to its stable state). Based on this calculation, we are able to determine the optimal sample schemes for studying temporal dynamics. Conclusions There is evidence of temporal continuity for at least some genera; there is clear evidence of a stable state; and the optimal sampling frequency for studying temporal dynamics is in the range of one sample every 0.8–3.2 days.
The enrichment of CD44 in exosomes from breast cancer cells treated with doxorubicin promotes chemoresistance
Authors: wang xiaohong , cheng kai , zhang guoqiang , yu yue , liu song , hua yitong , guo fengli , li xiaoqiang , zou weiwei , sun hongguang , xu shujian , dong jianli , yang zhenlin 
Published: February 2020

Abstract
Background: Exosomes have been shown to be associated with chemotherapy resistance transmission between cancer cells. However, the cargo and function of exosomes changed in response to doxorubicin remains unclear. Methods: We compared proteome profiles of exosomes extracted from the supernatant of MCF-7(S/Exo) and MCF-7/ADR(A/Exo) cells. We confirmed the differential expression of the candidate target-exosomic-CD44 by immune gold staining and western blot. We further studied the changes of chemosensitivity and CD44 expression in MCF-7 cells co-incubated with A/Exo. We analyzed the levels of exosomal CD44 from patient plasma, and compared the sensitivity and specificity of exosomic CD44 and plasma CD44 on diagnosis of chemoresistance. We modified the MCF-7-derived exosomes loaded with siRNA against CD44 to observe the effects of targeting reduced CD44 expression in lumimal A breast cancer cells. Results: DOX increased the exosomes release from MCF-7/ADR cells and the exosomes mediated proteins intercellular transfer in breast cancer chemoresistance regulation. The candidate target of CD44 in A/Exo was much higher than in S/Exo and the increase levels of exosomic CD44 (21.65-fold) was much higher than cellular CD44 (6.55-fold). The same results were obtained in clinical samples. Exosome-siRNA targeted CD44 (Exos-siCD44) could efficiently targeted to silence its expression. When co-cultured on Exos-siCD44, breast cancer cells exhibited reduced cell proliferation and enhanced susceptibility to DOX and the same phenomenon was observed in mice. Conclusion：Drug-resistant breast cancer cells spread resistance capacity to sensitive ones by releasing exosomes to transfer proteins in intercellular.
Multiple Cross Displacement Amplification-a more applicable technique in detecting Pseudomonas Aeruginosa of Ventilator-associated Pneumonia( VAP)
Authors: Wang Juxiang , Chen Huimin , Lin Xiaomin , Ji Chengyi , Chen Bin 
Published: February 2020

Abstract
Background Early and rapid identification of P seudomonas aeruginosa (PA) in patients with suspected ventilator-associated pneumonia (VAP)provides theoretical clinical advantages in therapeutic optimization strategies. Methods The PA-MCDA assay was conducted at an isothermal temperature during the amplification stage, and products were visually detected by color changes. The entire process was completed within 1 h. A total of 77 strains, including PA species and various other species of non- PA were used to evaluate PA -MCDA assays. Bronchoalveolar lavage fluid (BALF) of suspected VAP patients were examined by the MCDA assay. Results. The MCDA assay exhibited a 100 percent analytical specificity in detecting PA from all 77 strains, and the limits of detection limit were as low as 100 fg DNA per reaction. A temperature of 65ºC was recommended as standard during the amplification stage. Of all 26 BALF specimens, the approach could recognize 8 PA from the BALF specimens without the need for bacterial culture, from which, 7 were positive and 1 was negative. Conclusions. The instrument-free platform of the MCDA assay makes it a simple, rapid and applicable procedure for “on-site” diagnosis and point-of-care testing for the presence of PA without the need for specific bacterial culture.
Cancer development in COPD patients: retrospective analysis of the National Health Insurance Service-National Sample Cohort in Korea
Authors: Ahn Song Vogue , Park Bumhee , Jung Jin Hee , Lee Eunyoung , Park Ji Eun , Sheen Seung Soo , Park Kwang Joo , Park Jae Bum , Park Hae-Sim , Park Joo Hun 
Published: February 2020

Abstract
Background COPD is a well-known risk factor for lung cancer, independent of smoking behavior. By investigating the retrospective National Health Insurance Service-National Sample Cohort (NHIS-NSC) in Korea, this study attempted to prove our hypothesis that COPD is a risk factor for major cancers developing outside of the lungs. We also aimed to investigate the environmental factors associated with the development of lung cancer in COPD patients. Methods This study analyzed data from the NHIS-NSC over a 12-year period. Among the 514,795 subjects in the NHIS-NSC, 20,837 patients who were diagnosed with any cancer from 2002 to 2003 were excluded. Finally, this cohort enrolled four arms, the healthy control group (N=127,884), never-smokers with COPD (N=29,799), former smokers with COPD (N=3,267), and smokers with COPD (N=8,335). Results Over a 12-year period, lung cancer developed in 1.27% of the never-smokers with COPD, 2.97% of the former smokers with COPD, and 4.79% of smokers with COPD much higher than in 0.63% of the healthy control group (p < 0.001). Multivariate analyses showed that COPD, regardless of smoking status, contributed to the development of lung cancer but was not linked with any other major cancers, including stomach cancer, colorectal cancer, liver cancer and acute myeloid leukemia (p < 0.01). Age, male gender, lower BMI, low exercise level, smoking, and COPD were independent factors associated with the development of lung cancer (p< 0.01) Conclusion Our data suggest that COPD was an independent risk factor for the development of lung cancer in the Korean population, regardless of smoking status but other major cancers were not linked with COPD.
A long non-coding RNA, HOTAIR, promotes osteoarthritis development by inhibiting WIF-1 expression and activating Wnt pathway
Authors: Yang Yang , Xing Dan , Wang Yawei , Jia Haobo , Li Bing , Li Jiao Jiao 
Published: February 2020

Abstract
Background: Long noncoding RNAs (lncRNAs) are recently found to be critical regulators of the epigenome. However, our knowledge of their role in osteoarthritis (OA) development is limited. This study investigates the mechanism by which HOTAIR, a key lncRNA with elevated expression in OA, affects OA disease progression. Results: HOTAIR expression was greatly elevated in osteoarthritic compared to normal chondrocytes. Silencing and over-expression of HOTAIR in SW1353 cells respectively reduced and increased the expression of genes associated with cartilage degradation in OA. Investigation of molecular pathways revealed that HOTAIR acted directly on Wnt inhibitory factor 1 (WIF-1) by increasing histone H3K27 trimethylation in the WIF-1 promoter, leading to WIF-1 repression that favours activation of the Wnt/β-catenin pathway. Conclusions: Activation of Wnt/β-catenin signalling by HOTAIR through WIF-1 repression in osteoarthritic chondrocytes increases catabolic gene expression and promotes cartilage degradation. This is the first study to demonstrate a direct link between HOTAIR, WIF-1 and OA progression, which may be useful for future investigations into disease biomarkers or therapeutic targets.
Evaluation of TaqMan Array Card (TAC) for the Detection of 28 Respiratory Pathogens
Authors: Liu Keke , Jing Hongbo , Chen Ying , Zheng Xin , Jiang Hua , Kong Decong , Zheng Yvling , Chen Shuiping , Liu Peng , Jiang Yongqiang 
Published: February 2020

AbstractBackground: Respiratory infections are a serious threat to human health. So, rapid detection of all respiratory pathogens can facilitate prompt treatment and prevent the deterioration of respiratory disease. Previously published primers and probes of the TaqMan array card (TAC) for respiratory pathogens are not sensitive to Chinese clinical specimens. This study aimed to develop and improve the TAC assay to detect 28 respiratory viral and bacterial pathogens in a Chinese population. Methods: To improve the sensitivity, we redesigned the primers and probes, and labeled the probes with minor groove binders. The amplification efficiency, sensitivity, and specificity of the primers and probes were determined using target-gene containing standard plasmids. The detection performance of the TAC was evaluated on 754 clinical specimens and the results were compared with those from conventional methods. Results: The performance of the TAC assay was evaluated using 754 clinical throat swab samples and the results were compared with those from gold-standard methods. The sensitivity and specificity were 95.4% and 96.6%, respectively. The lowest detection limit of the TAC was 10 to 100 copies/μL. Conclusions: TAC is an efficient, accurate, and high-throughput approach to detecting multiple respiratory pathogens simultaneously and is a promising tool for the identification of pathogen outbreaks.