bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of differentially expressed genes in Cushing's disease by integrated bioinformatics analysis
Authors: Lv Tingting , Yu Haoying , Ren Shuyue , Wang Jingrong , Sun Lan , Du Guanhua 
Published: May 2020

Abstract
Background Cushing's disease is a rare and little-known disease, and the individualization of drug treatment varies greatly. Studies have shown that the gene expression profile of Cushing's disease is related to its clinical characteristics. Therefore, the study aims to identify key differential genes between the age and size of tumors through bioinformatics technology, thus providing a theoretical basis for personalized targeted therapy of Cushing's disease. Methods Downloading the gene expression microarray (GSE93825) data from the Gene Expression Omnibus (GEO) database and obtaining differentially expressed genes (DEGs) of different tumor sizes and ages through GEO2R. The DAVID database, Cytoscape and String platforms were utilized for functional enrichment analysis and protein-protein interaction (PPI) network analysis on selected differential genes. Results First, 96 DEGs were identified between macroadenoma (MAC) and microadenoma (MIC), which initially proved the different gene expression characteristics between them. Second, a total of 2128 DEGs were identified in MAC age group. The top five hub genes of the PPI network were GNGT2, LPAR3, PDYN, GRM3, and HTR1D. A total of 16 DEGs were identified in MIC age group. In addition, 88 DEGs were identified in younger MAC and MIC groups. The top five hub genes included LEP, PTGS2, STAT6, CXCL12, and ITPKB. 299 DEGs were identified in senior MAC and MIC groups. The first five hub genes were CCR7, LPAR2, CXCR5, ADCY3, and TAS2R14. By virtue of DAVID and Cytoscape software, the function enrichment analysis and core module analysis were performed successfully. Conclusions In summary, our research shows through bioinformatics analysis that different gene expression profiles of Cushing's disease are related to the size and age of the tumor, which may provide new insights into the molecular pathogenesis of Cushing's disease. These hub genes may be used for accurate diagnosis and treatment of Cushing's disease.
Effects of Luseogliflozin on Left Ventricular Diastolic Function in Patients with Type 2 Diabetes and Established Cardiovascular Disease.
Authors: Ina Yujiro , Kishi Takuya , Sekiguchi Naotaka 
Published: May 2020

Abstract
Background:

This study aimed to evaluate the effect of luseogliflozin, an inhibitor of sodium-glucose cotransporter 2 (SGLT2), on left ventricular (LV) diastolic function in patients with type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD).
Methods:

We enrolled 25 patients with T2DM and CVD and performed physical examinations, blood tests, and echocardiography before and 24 weeks after luseogliflozin treatment. The primary endpoint was defined as a change in the septal E/e′ ratio as a parameter of LV diastolic function.
Results:

Luseogliflozin administered for 24 weeks significantly reduced HbA1c levels (8.2 ± 1.2% to 7.4 ± 0.6%, p < 0.01) and systolic blood pressure (125.6 ± 18.1 mmHg to 119.3 ± 16.8 mmHg, p = 0.04) compared to baseline. Luseogliflozin significantly reduced left atrial diameter (42.2 ± 5.7 mm to 39.9 ± 6.8 mm, p = 0.01) and LV diameter (diastolic, 49.5 ± 6.9 mm to 47.6 ± 7.6 mm, p = 0.01; systolic, 35.8 ± 9.1 mm to 33.9 ± 9.8 mm, p < 0.01). Early diastolic mitral annular tissue (e′) velocity and septal E/e′ ratio were significantly improved in the group of e′ velocity < 6.0 cm/sec of baseline (e′ velocity, 4.8 ± 0.6 cm/sec to 5.8 ± 0.9 cm/sec, p < 0.01; septal E/e′ ratio, 13.0 ± 4.9 to 10.9 ± 3.4, p = 0.03, respectively).
Conclusions:

These results suggest the possibility that luseogliflozin improves overt LV diastolic function in patients with T2DM and CVD.
Stachyose improves the anti-diabetic effects of berberine by regulating intestinal microbiota and SCFAs in spontaneous type 2 diabetic KKAy mice
Authors: Cao Hui , Li Cai-Na , Lei Lei , Wang Xing , Liu Shuai-Nan , Liu Quan , Huan Yi , Sun Su-Juan , Shen Zhu-Fang 
Published: May 2020

Abstract
Background: Berberine (BBR) has the beneficial effects of anti-inflammation, anti-bacteria, and anti-diabetes. The clinical application of BBR has been hindered by its poor gastrointestinal absorption. Stachyose (Sta), a prebiotic agent, improves the composition of gut microbiota and benefits for diabetes. We therefore investigated whether Sta improves the anti-diabetic actions of BBR using type 2 diabetic KKAy mice.Methods: KKAy mice were randomly divided into four groups: Con, Sta (200 mg/kg), BBR (100 mg/kg), and BBR+Sta (BBR: 100 mg/kg, Sta: 200 mg/kg). Mice were administered intragastrically once daily for 8 weeks. The mice weight, glycemia, glycated hemoglobin, and levels of insulin, glucagon, and inflammatory cytokines were monitored. Oral glucose tolerance tests and insulin tolerance tests were performed; protein and gene expression levels were detected by Western blot and qRT-PCR, respectively; gut microbiota and short-chain fatty acids (SCFAs) in feces were analyzed.Results: The combination of BBR and Sta is more effective than BBR alone in blood glucose control, improvement of insulin resistance and islet functions, inflammatory mediators decrease, and maintenance of intestinal barrier integrity. Gut microbiota analysis demonstrates that both BBR and combination treatments enhance the abundance of Bacteroidaceae and Akkermansiaceae and decrease Lachnospiraceae levels, whereas Akkermansiaceae elevation due to the administration of BBR with Sta is more significant than BBR alone. Interestingly, the proportion of Lactobacillaceae increases with combination treatment, but is diminished by BBR treatment. Additionally, BBR with Sta significantly reduces the concentrations of fecal SCFAs compared to BBR.Conclusions: The combination of BBR and Sta imparts better effects on the maintenance of glycemia and intestinal homeostasis than BBR alone by modulating gut microbiota and SCFAs, thereby providing a novel approach for the treatment of type 2 diabetes mellitus.
Estimating the effectiveness of non-pharmaceutical interventions on COVID-19 control in South Korea
Authors: Min Kyung-Duk , Kang Heewon , Lee Ju-Yeun , Jeon Seonghee , Cho Sung-il 
Published: May 2020

Abstract
Background: The coronavirus disease 2019 (COVID-19) pandemic has posed significant global public health challenges and created a substantial economic burden. South Korea has experienced an extensive outbreak, which was linked to a religion-related super-spreading event. However, the implementation of various non-pharmaceutical interventions (NPIs), including social distancing, spring semester postponing, and extensive testing and contact tracing controlled the epidemic. Herein, we estimated the effectiveness of each NPI using a simulation model.Methods: A compartment model with a susceptible-exposed-infectious-quarantined-hospitalized (SEIQH) structure was employed. Using the Monte-Carlo-Markov-Chain algorithm with Gibbs’ sampling method, we estimated the time-varying effective contact rate to calibrate the model with the reported daily new confirmed cases from February 12th to March 31st (7 weeks). Moreover, we conducted scenario analyses by adjusting the parameters to estimate the effectiveness of NPI.Results: Relaxed social distancing among adults would have increased the number of cases 27-fold until the end of March, and the epidemic curve would have been similar to other high burden countries. Spring semester non-postponement would have increased the effective contact rate 2·4-fold among individuals aged 0-19, while lower quarantine and detection rates would have increased the number of cases 1·4-fold. Conclusions: Among the three NPI measures, social distancing in adults showed the highest effectiveness. The substantial effect of social distancing should be considered for developing an exit strategy.
Prognostic significance of preoperative neutrophil-to-lymphocyte ratio in papillary renal cell carcinoma patients after receiving curative surgery based on a retrospective cohort
Authors: Zhang Zhilei , Yu Yongbo , Zheng Jilu , Zhang Mingxin , Niu Haitao 
Published: May 2020

Abstract
Background: Inflammatory response biomarkers have been studied as promising prognostic factors in renal cell carcinoma (RCC), but there were few studies focusing on the papillary renal cell carcinoma (PRCC), this study was performed to evaluate the prognostic value of preoperative neutrophil-to-lymphocyte ratio (NLR) in PRCC patients. Methods: Totally 90 PRCC patients after surgical treatment selected from 284 non-clear renal cell carcinoma (nccRCC) were enrolled from our institution between 2012 and 2019. The optimal cutoff value of NLR was assessed by receiver operating curve (ROC), Kaplan–Meier method and Cox's proportional hazards regression models were performed to analyze association of NLR to overall survival (OS). In addition, the abilities of tumor-node-metastasis (TNM) stage, NLR and NLR-TNM system in predicting survival were compared by ROC curves. Results: 2.39 as the threshold value of NLR was determined by ROC curve in evaluating OS. Patients with NLR≥2.39 were associated with advanced TNM stage (P＜0.001), larger tumors (P＜0.05) and hypoalbuminemia (P＜0.05) compared to the low NLR group, these patients were also significantly exhibited worse overall survival outcomes(P＜0.05). NLR was a significantly independent prognostic indicator by univariate and multivariate analyses (HR = 5.870, P＜0.05). Furthermore, TNM stage and NLR were integrated and the area under curve (AUC) of NLR-TNM system was larger than that of TNM system when predicting overall survival (0.801 VS 0.761), but there was no difference between them (P=0.413).Conclusion: A high preoperative NLR was associated with poor clinical and pathologic parameters of patients with PRCC, moreover, NLR was also an independent prognostic factor of OS for patients with PRCC. The model of NLR-TNM system integrated NLR with TNM stage could improve the ability of predicting overall survival.
Alteration of lipid profile and prognostic value of lipids on the length of hospital stay in COVID-19 pneumonia patients
Authors: Chen Qin , Huang Minghan , Zhao Ziwen , Luo Yukun 
Published: May 2020

Abstract
Background

The outbreak of the novel coronavirus SARSCoV-2 (coronavirus disease 2019; COVID-19) has spread to most of countries in the world. The tight relationship of plasma lipids and COVID-19 pneumonia (NCIP-19) has not been well invested. To observe lipid profiles and their alterations in hospitalized patients with COVID-19 and evaluated the prognostic value of lipids for the length of hospital stay (LOS).
Methods

248 NCIP-19 cases aged 18 years or older were enrolled in this study. Serum lipids, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were detected at admission. In 68 severe cases, levels of serum lipids were subsequently detected every 5 ~ 10 days.
Results

At admission, median levels of TG, TC, HDL-C, and LDL-C in all patients, were 1.11 mmol/L, 4.00 mmol/L, 0.89 mmol/L and 2.11 mmol/L, respectively. Compared with common cases (n = 174), higher TG and HDL-C, lower LDL-C were observed in severe cases (n = 74). Levels of TC and LDL-C at admission were negatively correlated with LOS. In severe cases, the average levels of serum lipids were lowest at admission and gradually increased during hospitalization. Compared with the LOS ≤ 29d group, serum levels of TC, HDL-C, and LDL-C were significantly lower in the LOS > 29d group at admission; this lower trend always existed during the following tests for TC and LDL-C, but not for HDL-C and TG. Patients with LDL-C ≥ 1.70 mmol/L at admission showed a lower risk of LOS prolongation (adjusted HR = 0.557, 95% CI: 0.409–0.759, p < 0.001).
Conclusions

In NCIP-19, serum lipid levels were low at admission. Levels of TC and LDL-C at admission were negatively correlated with LOS. LDL-C < 1.7 mmol/L at admission may act as the independent predictor of LOS prolongation. In severe cases, the gradual increase of TC, LDL-C, and HDL-C during the hospitalization might indicate the gradual recovery of the disease.
Hepatocyte high-mobility group box 1 protects against steatosis and cellular stress during high fat diet feeding
Authors: Lin Minjie , Long Jungke , Li Wenbo , Yang Chenxuan , Loughran Patricia , O’Doherty Robert , Billiar Timothy R. , Deng Meihong , Scott Melanie J. 
Published: May 2020

Abstract
Background
Circulating HMGB1 plays important roles in the pathogenesis of NAFLD. Intracellular HMGB1 is critical for the biology of hepatocytes. However, the intracellular role of HMGB1 in hepatocellular steatosis is unknown. Therefore, we aimed to investigate the role of hepatocyte-specific HMGB1 (HC-HMGB1) in development of hepatic steatosis.
Methods
Wild type (WT) C57BL/6 and HC-HMGB1−/− mice were fed high-fat diet (HFD) or low-fat diet (LFD) for up to 16 weeks.
Results
As expected, HMGB1 translocated from nuclear into cytoplasm and released into circulation after HFD treatment. HC-HMGB1 deficiency significantly reduced circulating HMGB1, suggesting that hepatocyte is a major source of circulating HMGB1 during NAFLD. Unexpectedly, HC-HMGB1 deficiency promoted rapid weight gain with enhanced hepatic fat deposition compared with WT at as early as 4 weeks after HFD treatment. Furthermore, there was no difference between WT and HC-HMGB1−/− mice in glucose tolerance, energy expenditure, liver damage or systemic inflammation. Interestingly, hepatic gene expression related to FFA β-oxidation was significantly down-regulated in HC-HMGB1−/− mice compared with WT, and ER-stress markers were significantly higher in livers of HC-HMGB1−/− mice. In vitro experiments using primary mouse hepatocytes showed absence of HMGB1 increased FFA-induced intracellular lipid accumulation, accompanied by increased ER-stress, significant downregulation of FFA β-oxidation, and reduced oxidative phosphorylation.
Conclusions
Our findings suggest hepatocyte HMGB1 protects against dysregulated lipid metabolism via maintenance of β-oxidation and prevention of ER-stress. This represents a novel mechanism for HMGB1-regulation of hepatocellular steatosis, and suggests that stabilizing HMGB1 in hepatocytes may be effective strategies for prevention and treatment of NAFLD.
Integrating heart rate variability and electrochemical skin conductance as severity screening of cardiovascular autonomic neuropathy in type 2 diabetes
Authors: Lai Yun-Ru , Cheng Ben-Chung , Tsai Nai-Wen , Chiu Wen-Chan , Chen Jung-Fu , Huang Chih-Cheng , Lu Cheng-Hsien 
Published: May 2020

Abstract
Background: Clinical studies show that either heart rate variability (HRV) or electrochemical skin conductance (ESC) alone can serve as a simple and objective method for screening cardiovascular autonomic neuropathy (CAN). We tested the hypothesis that combining these two quantitative approaches can provide a better estimate of CAN severity in patients with type 2 diabetes (T2DM) who had already suffered from CAN in outpatient clinics.Methods: Each patient received a complete battery of cardiovascular autonomic reflex tests (CARTs), with ESC measured by SUDOSCAN, time domain measured by standard deviation of all normal RR intervals (SDNN) and frequency domain of HRV (low frequency [LF], high frequency [HF], and LF/HF ratio), and peripheral blood studies for vascular risk factors. Severity of CAN was measured by CAN score.Results: The 90 T2DM patients included 50 males and 40 females. Those with more severe CAN had a higher CAN score value (P<0.0001) and lower values in feet ESC (P=0.023) and SDNN (P<0.0001). Stepwise linear regression analysis also showed that feet ESC and SDNN value (P<0.0001 and P<0.0001) were significantly associated with CAN score, respectively.Conclusions: Based on our results, a combination of electrophysiologic biomarkers (SDNN and feet ESC) as a test battery can improve the diagnostic accuracy and reinforce the accuracy in estimating CAN severity and can serve as a time-effective screening service in outpatient clinics.
Myth Versus Reality - Emergency Department Revisits Within 72 Hours, At A Tertiary Care Hospital In Saudi Arabia.
Authors: Zakria Imran , Ala'ddin Adel , Alnatour Mourad Alnatour , Bashir Mwaffak 
Published: May 2020

Abstract
Any return to ED within a short time frame after discharge is classed as “revisit”. Revisits’ study is required to understand the dynamics governing these attendances, quality and safety of medical care delivered, and for correct system designing, efficient use of resources as well as benchmarking for future referencing. Methods: Retrospective review of electronic patient database was undertaken for one summer and one winter months at our institution. All patients were included who revisited ED within 72 hours of initial visit. Detailed study was carried out for first 100 revisit records for each of these months’ for demographics, timing as well as acuity of presentation, management and disposition. Results: 7473 patient visits were recorded for the study periods of 1 st to 30 th Nov 2018 (3754) and June 2019 (3719). 768 (387+381) of these were revisits within 72 hours, qualified for this study, 425 (250+275) of these were adults and 243 (137+106) were paediatric patients. Revisits’ male and female ratio was 57% and 43% respectively. Age distribution in years was 14 to 55 53%, 56-69 26%, paediatrics 8% and geriatrics 13%. Majority of index visits as well as revisits were between 14:00 and midnight (75% and 90% respectively). 44% visited within 24 hours after first visit while 36% in 25-48 hours and 20% during next 24 hours post discharge. Patient triage category 4 and 3 was (58% and 29%) at initial visit and (55% and 30%) at revisits, respectively. 40% of studied revisits were found to be scheduled! 56% re-attendances were family medicine and 30% speciality related. Only 14% of studied returns were deemed “validated ED revisits” making our revisit rate of 1.4% of all ED visits! 8% of studied revisit cases had specialty involvement prior to discharge at first visit. 14% of revisited cases were subsequently readmitted while rest were discharged. Conclusions: Overall 10% patients revisited our unit, but only 1.4% were found to be validated ED revisits. Many of these complex re-attendances were multifactorial and further work is required to explore various interventions and their effects on the addressable factors for revisits.
Antibiotics Treatment and Immune-checkpoint Inhibitors Efficacy: A Systematic Review and Meta-analysis
Authors: Hao Jie , Zhao Yang , He Jiangyi , Wang Yunlong , Dong Yan 
Published: May 2020

Abstract
Background: Immune-checkpoint inhibitors (ICIs) have been approved as 1st line therapy and benefit patients with advanced cancer. However, still many patients fail to achieve the significant efficacy, a predictor for precise patient selection is needed. The aim of our study is to determine whether the administration of antibiotics before or at the beginning of ICIs treatment is a prognostic factor of progression-free survival (PFS) and overall survival (OS) in patients with advanced cancer.Methods: A systematic search in PubMed, Embase, Cochrane and Web of Science databases was conducted using the search terms antibiotic, PD-1, PD-L1, CTLA-4, combined with cancer, tumor, neoplasm, or carcinoma. Data extraction was performed independently. Hazard ratio (HR) for PFS and OS of antibiotics (+) group vs antibiotics (-) group were pooled according to random or fixed-effects models. HRs with 95% confidence intervals (CIs) for PFS and OS were pooled to obtain prognostic information and aggregate values.Results: Nine studies including 1163 patients were included in this meta-analysis. By PFS analysis, antibiotics administration was associated with a significantly increased risk of disease progression (HR, 1.76; 95% CI, 1.37-2.26; P< 0.01). By OS analysis, antibiotics uptake also showed an HR in favor of death (HR, 1.7; 95% CI, 1.40-2.07; P< 0.01).Conclusions: Based on the existing evidence, antibiotics administration is a prognostic factor for reduced PFS and OS in patients receiving ICIs treatment. The time interval between antibiotics administration and ICIs treatment should be considered.
10-year Follow-up of the Prospective, Double-blinded, Randomized, Controlled Study of Autologous Bone Marrow Buffy Coat Grafting Combined With Core Decompression in Patients With Avascular Necrosis of Femoral Head
Authors: Li Mengyuan , Ma Yuanchen , Fu Guangtao , Zhang Ruiying , Li Qingtian , Deng Zhantao , Zheng Minghao , Zheng Qiujian 
Published: May 2020

Abstract
Background: Avascular necrosis of femoral head (ANFH) is a severely disabling disease of hip.Several clinical trials have shown promising outcomes on the use of mesenchymal stem cells for treatment of ANFH but long-term clinical assessment is lacking. Previously we have reported two year follow up of a prospective, double-blinded, randomized, controlled study of autologous bone marrow buffy coatgrafting combined with core decompression in patients with ANFH. Here we reported the outcome of ten year follow up on the study.Methods:We recruited 43 (53 hips) patients from 2009 to 2010. The hips were randomly allocated to code decompression (CD) with and without bone marrowbuffy coat (BBC). Participants were followed at 24, 60, 120 months postoperatively. Visual analogue scale (VAS), Lequesne algofunctional index and Western Ontario and McMaster Universities Arthritis Index (WOMAC) osteoarthritis scoring were recorded. Survival rate analysis and the prognostic factor analysis were performed. The endpoint was defined as progression to Ficat stage IV or conversion to hip arthroplasty.Results: 31 patients (41 hips) were included in the final analysis. CD + BBC group scored better in subjective assessing scores compared with CD group. The average survival time was 102.3 months and 78.1 months for CD + BBC group and CD group, respectively (Log-rank test, P = 0.029). In the univariate COX proportional-hazards regression model, age [hazards ratio (HR) = 1.079, P = 0.047] and pre-operative Ficat stage (HR = 3.283, P = 0.028) indicated high risk for progression, while the use of BBC (HR = 0.332, P = 0.042) indicated low risk. Pre-operative Ficat stage IIIwas isolated as an independent risk factor for clinical failure in the multivariate model (HR = 3.743, P = 0.018).Conclusion: The outcome of ten year follow up on this prospective, double-blinded, randomized,controlled study showed that use of the autologous BBC in combined with core decompression is more effective than core decompression alone.TrialRegistration: ClinicalTrials.gov identifier NCT01613612. Registered 13 December 2011 – Retrospectively registered, https://clinicaltrials.gov/ct2/show/record/NCT01613612.