bluuebunny/crossref_metadata_2025_split huggingface dataset:
PGM5-AS1 impairs miR-587-mediated GDF10 inhibition and abrogates progression of prostate cancer
Authors: Du Lei , Gao Yongli 
Published: January 2021

AbstractBackgroundProstate cancer (PCa) is a leading cause of cancer-related death in males. Aberrant expression of long non-coding RNAs (lncRNAs) has been implicated in various human malignancies, including PCa. This study aims to clarify the inhibitory role of human PGM5 antisense RNA 1 (PGM5-AS1) in the proliferation and apoptosis of PCa cells.MethodsThe regulatory network of PGM5-AS1/microRNA-587 (miR-587)/growth and differentiation factor 10 (GDF10) axis was examined by dual-luciferase reporter gene assay, RNA-binding protein immunoprecipitation, and RNA pull down assay. We manipulated the expression of PGM5-AS1, miR-587 and GDF10 by transducing expression vectors, mimic, inhibitor, or short hairpin RNA into PCa cells, thus establishing their functions in cell proliferation and apoptosis. Additionally, we measured the tumorigenicity of PCa cells xenografted in nude mice.ResultsPGM5-AS1 is expressed at low levels in PCa cell lines. Forced overexpression of PGM5-AS1 restricted proliferation and facilitated apoptosis of PCa cells, manifesting in suppressed xenograft tumor growth in nude mice. Notably, PGM5-AS1 competitively bound to miR-587, which directly targets GDF10. We further validated that the anti-cancer role of PGM5-AS1 in PCa cells was achieved by binding to miR-587 to promote the expression of GDF10.ConclusionPGM5-AS1 upregulates GDF10 gene expression by competitively binding to miR-587, thus inhibiting proliferation and accelerating apoptosis of PCa cells.
Postoperative radiotherapy is associated with improved survival in pT1-2N1 oral and oropharyngeal cancer without adequate neck dissection
Authors: Yang Ching-Chieh , Kang Bor-Hwang , Liu Wen-Shan , Yin Chun-Hao , Lee Ching-Chih 
Published: January 2021

AbstractBackgroundTo assess the benefit of postoperative radiotherapy in patients with pT1-2N1M0 oral and oropharyngeal cancer by the quality of neck dissection.MethodsIn the Surveillance, Epidemiology, and End Results database, pT1-2N1M0 oral and oropharyngeal cancer patients treated by primary tumor resection and neck dissection with or without radiotherapy were included between 2004 and 2015. Univariate and multivariate analysis were used to explore the effect of adjuvant radiotherapy on 5-year overall survival (OS) and disease-specific survival (DSS) among different quality of neck dissection.ResultsOf the 1765 patients identified, 1108 (62.8%) had oral cancer, 1141 (64.6%) were men, and 1067 (60.5%) underwent adjuvant radiotherapy. After adjusting for confounding factors, postoperative radiotherapy reduced the adjusted hazard ratio (aHR) of 5-year OS to 0.64 (95% confidence interval [CI] 0.49–0.84) in those with < 18 lymph nodes (LNs) removed, but not in those with 19–24 LNs removed (aHR 0.78; 95% CI 0.73–1.13), and in those with ≥ 25 LNs removed (aHR 0.96; 95% CI 0.75–1.24). For 5-year DSS, similar effect was observed. The adjusted hazard ratio was 0.66 (95% confidence interval, 0.45–0.97) in those with < 18 LNs. The protective effect was not seen in those with 18–24 LNs (aHR 1.07; 95% CI 0.59–1.96), and in those with ≥ 25 LNs (aHR 1.12; 95% CI 0.81–1.56). Sensitivity testing also showed a robust protective effect of postoperative radiotherapy in patients with < 18 LNs removed.ConclusionRadiotherapy was associated with improved survival in pT1-2N1M0 oral and oropharyngeal cancer patients without adequate neck dissection.
Knockdown of long non-coding RNA LEF1-AS1 attenuates apoptosis and inflammatory injury of microglia cells following spinal cord injury
Authors: Cui Sheng-Yu , Zhang Wei , Cui Zhi-Ming , Yi Hong , Xu Da-Wei , Liu Wei , Zhu Xin-Hui 
Published: January 2021

Abstract
Background
Spinal cord injury (SCI) is associated with health burden both at personal and societal levels. Recent assessments on the role of lncRNAs in SCI regulation have matured. Therefore, to comprehensively explore the function of lncRNA LEF1-AS1 in SCI, there is an urgent need to understand its occurrence and development.

Methods
Using in vitro experiments, we used lipopolysaccharide (LPS) to treat and establish the SCI model primarily on microglial cells. Gain- and loss of function assays of LEF1-AS1 and miR-222-5p were conducted. Cell viability and apoptosis of microglial cells were assessed via CCK8 assay and flow cytometry, respectively. Adult Sprague-Dawley (SD) rats were randomly divided into four groups: Control, SCI, sh-NC, and sh-LEF-AS1 groups. ELISA test was used to determine the expression of TNF-α and IL-6, whereas the protein level of apoptotic-related markers (Bcl-2, Bax, and cleaved caspase-3) was assessed using Western blot technique.

Results
We revealed that LncRNA LEF1-AS1 was distinctly upregulated, whereas miR-222-5p was significantly downregulated in LPS-treated SCI and microglial cells. However, LEF1-AS1 knockdown enhanced cell viability, inhibited apoptosis, as well as inflammation of LPS-mediated microglial cells. On the contrary, miR-222-5p upregulation decreased cell viability, promoted apoptosis, and inflammation of microglial cells. Mechanistically, LEF1-AS1 served as a competitive endogenous RNA (ceRNA) by sponging miR-222-5p, targeting RAMP3. RAMP3 overexpression attenuated LEF1-AS1-mediated protective effects on LPS-mediated microglial cells from apoptosis and inflammation.

Conclusion
In summary, these findings ascertain that knockdown of LEF1-AS1 impedes SCI progression via the miR-222-5p/RAMP3 axis.
miR-1249-5p regulates the osteogenic differentiation of ADSCs by targeting PDX1
Authors: Yang Xiao-Mei , Song Ya-Qi , Li Liang , Liu Dong-Ming , Chen Guang-Dong 
Published: January 2021

Abstract
Background
Osteoporosis (OP) is an age-related systemic bone disease. MicroRNAs (miRNAs) are involved in the regulation of osteogenic differentiation. The purpose of this study was to explore the role and mechanism of miR-1249-5p for promoting osteogenic differentiation of adipose-derived stem cells (ADSCs).

Methods
GSE74209 dataset was retrieved from NCBI Gene Expression Omnibus (GEO) database and performed bioinformatic analyses. OP tissue and healthy control tissues were obtained and used for RT-PCR analyses. ADSCs were incubated with miR-1249-5p mimic, inhibitor and corresponding negative control (NC), alkaline phosphatase (ALP) staining, and Alizarin Red Staining (ARS) were then performed to assess the role of miR-1249-5p for osteogenesis of ADSCs. Targetscan online website and dual-luciferase reporter assay were performed to verify that the 3′-UTR of PDX1 mRNA is a direct target of miR-1249-5p. RT-PCR and western blot were also performed to identify the mechanism of miR-1249-5p for osteogenesis of ADSCs.

Results
A total of 170 differentially expressed miRNAs were selected, among which, 75 miRNAs were downregulated and 95 miRNAs were upregulated. Moreover, miR-1249-5p was decreased in OP patients, while showed a gradual increase with the extension of induction time. miR-1249-5p mimic significantly increased osteogenic differentiation capacity and p-PI3K and p-Akt protein levels. Luciferase activity in ADSCs co-transfected of miR-1249-5p mimic with PDX1-WT reporter plasmids was remarkably decreased, but there was no obvious change in miR-1249-5p mimic with PDX1-MUT reporter plasmids co-transfection group. Overexpression PDX1 could partially reverse the promotion effects of miR-1249-5p on osteogenesis of ADSCs.

Conclusion
In conclusion, miR-1249-5p promotes osteogenic differentiation of ADSCs by targeting PDX1 through the PI3K/Akt signaling pathway.
Research of insomnia on traditional Chinese medicine diagnosis and treatment based on machine learning
Authors: Tang Yuqi , Li Zechen , Yang Dongdong , Fang Yu , Gao Shanshan , Liang Shan , Liu Tao 
Published: January 2021

AbstractBackgroundInsomnia as one of the dominant diseases of traditional Chinese medicine (TCM) has been extensively studied in recent years. To explore the novel approaches of research on TCM diagnosis and treatment, this paper presents a strategy for the research of insomnia based on machine learning.MethodsFirst of all, 654 insomnia cases have been collected from an experienced doctor of TCM as sample data. Secondly, in the light of the characteristics of TCM diagnosis and treatment, the contents of research samples have been divided into four parts: the basic information, the four diagnostic methods, the treatment based on syndrome differentiation and the main prescription. And then, these four parts have been analyzed by three analysis methods, including frequency analysis, association rules and hierarchical cluster analysis. Finally, a comprehensive study of the whole four parts has been conducted by random forest.ResultsResearches of the above four parts revealed some essential connections. Simultaneously, based on the algorithm model established by the random forest, the accuracy of predicting the main prescription by the combinations of the four diagnostic methods and the treatment based on syndrome differentiation was 0.85. Furthermore, having been extracted features through applying the random forest, the syndrome differentiation of five zang-organs was proven to be the most significant parameter of the TCM diagnosis and treatment.ConclusionsThe results indicate that the machine learning methods are worthy of being adopted to study the dominant diseases of TCM for exploring the crucial rules of the diagnosis and treatment.
The impact of a perioperative pulmonary care bundle implementation on postoperative outcomes in 1,665 surgical cancer patients: experience from a tertiary referral cancer center in Jordan
Authors: Abdel Jalil Riad , Al-Najjar Hani , Abou Chaar Mohamad K. , Al-Masri Mahmoud , Daoud Faiez , Al-Ebous Ali , Dabous Ali , Shehadeh Ahmad M. , Abdel Al Samer , Alawneh Fade , Al-Qudah Obada , Al-Kharabsheh Mohammad , Al-Odat Ghazi , Mohammad Iqbal , Hussein Najah , Hudaip Zeinab , Al-Tbakhi Asma , Aqel Flsteen 
Published: January 2021

Abstract
Background
Postoperative pulmonary complications can be a major catastrophic consequence of major surgeries and can lead to increased morbidity, mortality, hospital stay, and cost. Many protocols have been tried to reduce serious adverse outcomes with effective strategies including a bundle of preoperative, intraoperative and postoperative techniques. Using these techniques maybe challenging in developing countries with limited resources even in specialized centers.

Methods
A before-and-after trial comparing our data from the national surgical quality improvement program (NSQIP) based on their reports. Data was collected prospectively for the patients who underwent major surgeries at King Hussein Cancer Center during the year 2017 when the use of the perioperative pulmonary care bundle was mandatory to all surgery teams and compared it with the data collected retrospectively for the patients who underwent the same type of surgeries in the year 2016 when the use of such a bundle was optional. The primary end point is the decrease in incidence of postoperative pulmonary complications. Simple descriptive statistical analysis was used to obtain results.

Results
The potential risk factors for postoperative pulmonary complications for 1665 patients divided into 2 groups (2016 vs. 2017); 764 (45.9%) vs. 901 (54.1%), respectively. There were no significant differences regarding gender (male 46.7% vs. 46.4%, P value = 0.891, female 53.3% vs. 53.6%, P value = 0.39), mean of age (53.5 year vs. 5.28 year, P value = 0.296), mean of body mass index (BMI) (28.6 vs. 6%, 28.6, P value = 0.95), smoking status; (69.6% vs. 65.1%, P value = 0.052), ventilator use (0.3% vs. 0.4% P value = 0.693) and chronic obstructive pulmonary disease (1.4% vs. 1.4 with, P value = 0.996).The data showed a significant reduction in postoperative pneumonia between the 2 groups (2016 vs. 2017) (2.7% vs. 0.9%, P value = 0.004) and showed a significant reduction in unplanned intubation, 1.4% in 2016 vs. 0.7% in 2017.

Conclusions
The standardization of perioperative pulmonary care bundle, including smoking cessation, perioperative pulmonary interventions and early mobilization, significantly reduces the incidence of postoperative pulmonary complications in cancer patients. This technique's implementation was feasible easily even with limited resources in a developing country like Jordan.
Characteristics and clinical outcomes of culture-negative and culture-positive septic shock: a single-center retrospective cohort study
Authors: Kim June-sung , Kim Youn-Jung , Kim Won Young 
Published: January 2021

Abstract
Background
We evaluated the characteristics and outcomes of culture-negative versus culture-positive septic shock.

Methods
We performed a retrospective observational study of data from a prospective registry from 2014 to 2018. A total of 2,499 adult patients with septic shock were enrolled. The primary outcome was 90-day mortality, and the secondary outcomes were the length of hospital stay, a requirement for mechanical ventilation or renal replacement therapy, and in-hospital mortality.

Results
Of 1,718 patients with septic shock, 1,012 (58.9%) patients were culture-positive (blood 803, urine 302, sputum 102, others 204) and the median pathogen detection time was 9.5 h (aerobic 10.2 h and anaerobic 9.0 h). The most common site of culture-positive infection was the hepatobiliary tract (39.5%), while for the culture-negative it was the lower respiratory tract (38.2%). The culture-negative group had a lower mean body temperature (37.3 vs 37.7 ℃), lactate (2.5 vs. 3.2 mmol/L), C-reactive protein (11.1 vs 11.9 mg/dL), and sequential organ failure assessment score (7.0 vs. 8.0) than that of the culture-positive group. However, 90-day mortality between the groups was not significantly different (32.7 vs 32.2%, p = 0.83), and the other clinical outcomes also did not differ significantly. Moreover, a shorter culture detection time was correlated with a higher sequential organ failure assessment score but not with mortality.

Conclusion
Patients with septic shock are frequently culture-negative, especially in cases where the infection focus is in the lower respiratory tract. Although culture-negative was associated with a degree of organ dysfunction, it was not an independent predictor of death.
Venoarterial extracorporeal membrane oxygenation induces early immune alterations
Authors: Frerou Aurélien , Lesouhaitier Mathieu , Gregoire Murielle , Uhel Fabrice , Gacouin Arnaud , Reizine Florian , Moreau Caroline , Loirat Aurélie , Maamar Adel , Nesseler Nicolas , Anselmi Amedeo , Flecher Erwan , Verhoye Jean-Philippe , Le Tulzo Yves , Cogné Michel , Roussel Mikael , Tarte Karin , Tadié Jean-Marc 
Published: January 2021

Abstract
Background
Venoarterial extracorporeal membrane oxygenation (VA-ECMO) provides heart mechanical support in critically ill patients with cardiogenic shock. Despite important progresses in the management of patients under VA-ECMO, acquired infections remain extremely frequent and increase mortality rate. Since immune dysfunctions have been described in both critically ill patients and after surgery with cardiopulmonary bypass, VA-ECMO initiation may be responsible for immune alterations that may expose patients to nosocomial infections (NI). Therefore, in this prospective study, we aimed to study immune alterations induced within the first days by VA-ECMO initiation.

Methods
We studied immune alterations induced by VA-ECMO initiation using cytometry analysis to characterize immune cell changes and enzyme-linked immunosorbent assay (ELISA) to explore plasma cytokine levels. To analyze specific changes induced by VA-ECMO initiation, nine patients under VA-ECMO (VA-ECMO patients) were compared to nine patients with cardiogenic shock (control patients).

Results
Baseline immune parameters were similar between the two groups. VA-ECMO was associated with a significant increase in circulating immature neutrophils with a significant decrease in C5a receptor expression. Furthermore, we found that VA-ECMO initiation was followed by lymphocyte dysfunction along with myeloid-derived suppressor cells (MDSC) expansion. ELISA analysis revealed that VA-ECMO initiation was followed by an increase in pro-inflammatory cytokines such as IL-6, IL-8 and TNF-α along with IL-10, a highly immunosuppressive cytokine.

Conclusion
VA-ECMO is associated with early immune changes that may be responsible for innate and adaptive immune alterations that could confer an increased risk of infection.
Independent and interactive effect of sitting time and physical activity on prevalence of hyperuricemia: the Henan Rural Cohort Study
Authors: Dong Xiaokang , Li Yuqian , Zhang Lulu , Liu Xiaotian , Tu Runqi , Wang Yikang , Li Ruiying , Li Linlin , Hou Jian , Mao Zhenxing , Huo Wenqian , Wang Chongjian 
Published: January 2021

Abstract
Background
There are few studies on the hyperuricemia (HUA) and moderate to vigorous intensity physical activity (PA) and also hardly regarding sitting time (ST). The purpose of this study was to examine the independent and interactive association of PA and ST with HUA.

Methods
A cross-sectional analysis was performed on 38,855 participants (aged 18–79) enrolled from the Henan Rural Cohort Study at baseline (2015 to 2017). PA and ST levels were assessed by using the International Physical Activity Questionnaire (IPAQ). HUA was defined as a serum uric acid level of > 7.0 mg/dL for males and > 6.0 mg/dL for females. Multivariable logistic regression and linear regression models were applied to examine the independent association between PA or ST and HUA and serum uric acid level. Interaction plots were used to visualize the interaction effects of PA and ST on HUA.

Results
PA level was inversely related with serum uric acid level (β − 0.15, 95% confidence interval (CI) − 0.22, − 0.07), but ST was positively related with uric acid level (β 2.12, 95% CI 1.90, 2.34). Metabolic equivalent (MET-hour/day) was associated with decreased prevalence of HUA (odds ratio (OR) 0.97, 95% CI 0.96, 0.99), while per hour increased for ST was associated with increased HUA (OR 1.05, 95% CI 1.04, 1.06). The interaction of PA and ST was significant (P < 0.001).

Conclusion
Exposure to higher ST was independently related to increased prevalence of HUA, while vigorous PA with a decreased HUA prevalence. Meanwhile, higher daily ST might attenuate the protective effect of PA on HUA.

Trial registration
The Henan Rural Cohort Study has been registered at Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699).
Switching first-line targeted therapy after not reaching low disease activity within 6 months is superior to conservative approach: a propensity score-matched analysis from the ATTRA registry
Authors: Nekvindová Lucie , Vencovský Jiří , Pavelka Karel , Horák Pavel , Křístková Zlatuše , Závada Jakub 
Published: January 2021

AbstractBackgroundTreat-to-target (T2T) is a widely accepted strategy for patients with rheumatoid arthritis (RA). It recommends attaining a goal of at least low disease activity (LDA) within 6 months; otherwise, the current therapy should be modified. We aimed to investigate whether switching a first-line targeted therapy (TT) in patients not reaching LDA within 6 months leads to a higher probability of meeting LDA at the 12-month visit in daily clinical practice using data from Czech registry ATTRA.MethodsWe included patients with RA starting the first-line TT from 1 January 2012 to 31 January 2017 with at least 1-year follow-up. We created four mutually exclusive cohorts based on (1) switching to another TT within the first year and (2) reaching a treatment target (DAS28-ESR ≤ 3.2) at the 6-month visit. The primary outcome was the comparison of odds for reaching remission (REM) or LDA at the 12-month visit between patients switching and not switching TT after not reaching treatment target at 6 months. Before using logistic regression to estimate the odds ratio, we employed the propensity score to match patients at the 6-month visit.ResultsA total of 1275 patients were eligible for the analysis. Sixty-two patients switched within the first 5 months of the treatment before evaluating treatment response at the 6-month visit (C1); 598 patients reached the treatment target within 6 months of therapy (C2); 124 patients did not reach treatment response at 6-month visit and switched to another therapy (C3), and 491 patients continued with the same treatment despite not reaching LDA at the 6-month visit (C4). We matched 75 patients from cohort C3 and 75 patients from C4 using the propensity score. Patients following the T2T principle (C3) showed 2.8 (95% CI 1.4–5.8;p = 0.005) times increased likelihood of achieving REM/LDA at the 12-month visit compared to patients not following the T2T strategy (C4).ConclusionsIn daily clinical practice, the application of the T2T strategy is underused. Switching TT after not reaching REM/LDA within the first 6 months leads to a higher probability of achieving REM/LDA in RA patients at the 12-month visit.
Associations between metabolic syndrome and type of dementia: analysis based on the National Health Insurance Service database of Gangwon province in South Korea
Authors: Kim Yeo Jin , Kim Sang Mi , Jeong Dae Hyun , Lee Sang-Kyu , Ahn Moo-Eob , Ryu Ohk-Hyun 
Published: January 2021

Abstract
Background
Metabolic syndrome is a cluster of conditions that occur together, increasing the risk of cardiovascular disease. However, the relationship between metabolic syndrome and dementia has remained controversial. Using nationwide population cohort data, we investigated the association between metabolic syndrome and dementia, according to the dementia type.

Methods
We analyzed data of 84,144 individuals, in the aged group of more than 60 years, between January 1, 2009, to December 31, 2009, at Gangwon province by using the information of the (Korean) National Health Insurance Service. After eight years of gap, in 2017, we investigated the relationship between metabolic syndrome and dementia. We classified Dementia either as dementia of the Alzheimer type (AD) or vascular dementia (VD). AD and VD were defined as per the criteria of International Classification of Disease, Tenth Revision, Clinical Modification codes. Multiple logistic regression analyses examined the associations between metabolic syndrome or five metabolic syndrome components and dementia. Analyses included factors like age, sex, smoking, alcohol, physical inactivity, previous stroke, and previous cardiac disease.

Results
Metabolic syndrome was associated with AD (OR = 11.48, 95% CI 9.03–14.59), not with VD. Each of five components of metabolic syndrome were also associated with AD. (high serum triglycerides: OR = 1.87, 95% CI 1.60–2.19; high blood pressure: OR = 1.85, 95% CI 1.55–2.21; high glucose: OR = 1.77, 95% CI 1.52–2.06; abdominal obesity: OR = 1.88, 95% CI 1.57–2.25; low serum high-density lipoprotein cholesterol: OR = 1.91, 95% CI 1.63–2.24) However, among components of metabolic syndrome, only the high glucose level was associated with VD. (OR = 1.26, 95% CI 1.01–1.56) body mass index (BMI), fasting glucose, and smoking were also associated with AD. (BMI: OR = 0.951, 95% CI 0.927–0.975; fasting glucose: OR = 1.003, 95% CI 1.001–1.005; smoking: OR = 1.020, 95% CI 1.003–1.039) A history of the previous stroke was associated with both AD and VD. (AD: OR = 1.827, 95% CI 1.263–2.644; VD: OR 2.775, 95% CI 1.747–4.406)

Conclusions
Metabolic syndrome was associated with AD but not with VD. Patients with metabolic syndrome had an 11.48 times more likeliness to develop AD compared to those without metabolic syndrome. VD was associated only with several risk factors that could affect the vascular state rather than a metabolic syndrome. We suggested that the associations between metabolic syndrome and dementia would vary depending on the type of dementia.