bluuebunny/crossref_metadata_2025 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

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

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

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

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

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

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

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

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

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

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

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.
Antimicrobials in Chicken Commercial Feeds in Vietnam: A Three-Year Longitudinal Study Before A Nationwide Ban of Growth Promoters
Authors: Carrique-Mas Juan , Cuong Nguyen Van , Kiet Bach Tuan , Hien Bo Ve , Truong Bao Dinh , Phu Doan Hoang , Thwaites Guy , Choisy Marc
Published: May 2020

Background Antimicrobial growth promoters (AGPs) are included in commercial animal feed rations in many low- and middle-income countries. We measured antimicrobial use (AMU) in commercial feed products consumed by 338 small-scale chicken flocks in the Mekong Delta of Vietnam, before a nation-wide ban on AGPs which is to be phased in over the coming three years. We reviewed the labels of commercial feeds and calculated amounts of antimicrobial active ingredients (AAIs) given to flocks, highlighting those that did not comply with Government regulations.Results Thirty five of 99 different antimicrobial-containing feed products (35.3%) included at least one AAI. Eight different AAIs (avilamycin, bacitracin, chlortetracycline, colistin, enramycin, flavomycin, oxytetracycline, virginamycin) belonging to 5 classes were identified. Brooding feeds contained antimicrobials the most (51.2%), followed by grower (34.6%) and finisher feeds (12.5%). The average amount of AAIs given to flocks per kg of chicken at consumption time was 84.8 (SEM ± 9.3 mg). Quantitatively, chlortetracycline was consumed most (42.2 mg/kg SEM ± 0.34; 50.0% of total use), followed by enramycin (18.4 mg SEM ± 0.03, 21.8%) and bacitracin (16.4 mg SEM ± 0.20, 19.4%). Antimicrobials in commercial feeds were more commonly given to flocks in the earlier part of the production cycle. A total of 10 (9.3%) products were not compliant with existing Vietnamese regulation (06/2016/TT-BNNPTNT) either because they included a non-authorised AAI (4), had AAIs over the permitted limits (4), or both (2).Conclusions and recommendation We found a discrepancy between current legislation and the types and quantities of AGPs found in chicken feeds; this may be a challenge in coming years when the full ban is implemented, and would require that the authorities step up monitoring efforts. Results from this study should encourage discussion about policies on AGPs in low- and middle-income countries.
Radiogenomic analysis of cervical lymph node metastasis in papillary thyroid carcinoma: A preliminary study
Authors: Tong Yuyang , Sun Peixuan , Huang Yunxia , Zhou Jin , Yong Juanjuan , Guo Yi , Yu Jinhua , Wang Yuanyuan , Zhou Shichong , Chang Cai
Published: May 2020

Background

Papillary thyroid carcinoma (PTC) is characterized by frequent metastasis to cervical lymph nodes (CLNs), and the presence of lymph node metastasis at diagnosis has a significant impact on the surgical approach. Therefore, we established a radiomic signature to predict the CLN status of PTC patients using preoperative thyroid ultrasound and investigated the association between the radiomic features and underlying molecular characteristics of PTC tumours.
Methods

A radiogenomic map linking radiomics features to gene modules was constructed, and immunohistochemistry was performed to validate key associations. In all, 180 patients were enrolled in this prospective study, and 47 radiomic features, including tumour size, shape, position, margin, echo pattern and calcification, were extracted. Total protein extracted from 49 tumour samples was analysed with LC/MS and iTRAQ technology. Gene modules acquired by clustering were chosen for their diagnostic significance. A radiogenomic map linking radiomic features to gene modules was constructed with the Spearman correlation matrix. Immunohistochemistry was performed to validate key associations between radiomic features and gene modules.
Results

The diagnostic performance of radiomics signature was better than that of the ultrasound-based method in predicting CLN status. Weighted gene co-expression network analysis generated 16 gene modules, and a radiogenomic map with nine significant correlations between radiomics features and gene modules was created. For example, the feature ‘minimum calcification area’ was significantly associated with module MEblue, which represents cell-cell adhesion and glycolysis. Immunohistochemistry showed that LAMC1 and THBS1 expression was associated with several radiomics features.
Conclusions

The radiomic signature proposed here has the potential to noninvasively predict the CLN status in PTC patients. Merging imaging phenotypes with genomic data could allow the noninvasive identification of the molecular properties of PTC tumours, which would support clinical decision making with personalized management.
Trail registration:

This prospective study was approved by the ethics committee of the Fudan University Shanghai Cancer Centre (1809191-1-NSFC) in July 2018.
Identifying emerging trends in rheumatoid arthritis research: A scientometric analysis
Authors: Li Xiang , Chen Gong , Seery Samuel , Zhao Zhehui , Zhang Haijing , Peng Ying , Wu Lianqiu
Published: May 2020

Background Rheumatoid arthritis (RA) is a systemic autoimmune disease, characterized as chronic and progressive with acute inflammatory attacks. RA is highly prevalent across all societies and over the past two decades there has been substantial effort to improve diagnostics and therapeutics.Methods We searched for pertinent studies using CiteSpace and created maps to understand the intellectual structure of RA research. Pertinent studies over the past two decades were retrieved from Web of Science. Scientometric analysis in this study includes time distribution, cluster analysis, time-zones and time-lines of keywords, as well as burst detection.Results Our analysis has revealed a steady upward trend in publications from 2010 until 2018 which perhaps reflects growing global concern and investment. While the etiology of RA appears unknown, there is a plethora of studies into pathological mechanisms, diagnostics and drug development through one of the phases of basic and clinical research. RA pathogenesis has been shown to involve immune cells, including T cells, B cells, macrophages and synoviocytes which have a key role in invasive synovium and joint inflammation. X-rays and blood testing can support differential diagnostics, and there are a number of treatments available which are selected depending upon RA staging.Conclusions TNF-α, apoptosis, pathogenesis, and NF-κB are the most frequently used terms across this specialism in 2020. These terms represent the new theoretical understanding and necessitates further research because they may guide patient selection and more individualised RA care.
Physical Function and Clinical Outcomes in Hemodialysis Patients: The China Dialysis Outcomes and Practice Pattern Study
Authors: Niu Qingyu , Zhao Xinju , Gan Liangying , Liang Xinling , Ni Zhaohui , Chen Xiaonong , Chen Yuqing , Hou Fan Fan , Zuo Li
Published: May 2020

Background: Hemodialysis (HD) patients usually have impaired physical function compared with general population. Self-reported physical function is a simple method to implement in daily dialysis care. This study aimed to examine the association of self-reported physical function with clinical outcomes of HD patients.Methods: Dialysis Outcomes and Practice Patterns Study (DOPPS) is a prospective cohort study. Data on 1427 HD patients in China DOPPS5 were analyzed. Self-reported physical function was characterized by 2 items of ‘moderate activities limited level’ and ’climbing stairs limited level’. Demographic data, comorbidities, hospitalization and death records were collected from patients’ records. Associations between physical function and outcomes were analyzed using COX regression models. The generalized linear mixed models were used to examine correlates of physical function limited level.Results: Compared to ‘limited a lot’ in moderate activities, ‘limited a little’ and ‘not limited at all’ groups were associated with lower all-cause mortality after adjusted for covariates (HR: 0.652, 95% CI: 0.435-0.977 and HR: 0.472, 95% CI: 0.241-0.927, respectively). And not limited in moderate activities was associated with lower risk of hospitalization compared with ‘limited a lot’ group after adjusted for covariates (HR: 0.747, 95% CI: 0.570-0.978). Meanwhile, compared to ‘limited a lot’ in climbing stairs, ‘limited a little’ and ‘not limited at all’ groups were associated with lower all-cause mortality (HR: 0.574, 95% CI: 0.380-0.865 and HR: 0.472, 95% CI: 0.293-0.762, respectively) but not hospitalization after fully adjusted. Factors including old age, female gender, longer dialysis vintage, catheter use, low serum albumin and combining with diabetes, coronary artery disease and cerebrovascular disease were related to higher limited levels of physical function (P < 0.05).Conclusion: Higher limited levels in self-reported physical function were associated with higher risk of all-cause mortality and hospitalization in HD patients.
Knocking out Analysis of the CpxP gene using Crispr/Cas9 in Escherichia coli MG1655
Authors: he xiaoliang , Ren Yuwen , Meng Wanli , Yu Xinran , Zhou Xiaohui
Published: May 2020

Based on the analysis of CpxP genes among Escherichia coli strains, CpxP gene-targeting short guide RNA (sgRNA) was designed and inserted into the pGL3-MGP-RNA. The donor sequences (MG-HR) for homologous repair were designed and cloned by PCR. MG-HR and pGL3-MGP-RNA were transformed into E. coli MG1655 (pCas9). The CpxP gene expression cassette was amplified by PCR and subcloned into pBBR1MCS-2. Then the pBBR-CpxP was independently transformed into E. coli MG1655. The results of motility experiment suggest that CpxP gene had a significant effect on the movement ability of E. coli strain. The CpxP protein had a significant inhibition of bacterial activity. The lastest 81 CpxP proteins sequences were selected and analyzed by multi-sequence alignment and molecular cluster. The CpxP proteins were roughly divided into three categories. Our results suggest that the CpxP protein was involved in bacterial motility, infection and pathogenicity.
Infrequent home-cooked meal consumption is related to the inadequacy of dietary fibre and minerals intake among Japanese adults aged 18-64 years: analysis from the 2015 National Health and Nutrition Survey
Authors: Matsumoto Mai , Saito Aki , Okada Chika , Okada Emiko , Takimoto Hidemi
Published: May 2020

Background: Consumption of home-cooked meals may lead to better nutritional intake. Few studies have examined the effect of frequency of home-cooked meal consumption on inadequacy of nutritional intake based on nutritional standards. We therefore aimed to examine the association between the frequency of home-cooked meal consumption and nutrient intake inadequacy among Japanese adults.Methods: This study was a secondary analysis of the 2015 National Health and Nutrition survey in Japan, involving 921 men and 1300 women aged 18–64 years, a cross-sectional survey. The frequency of home-cooked meal consumption was determined using two questions enquiring about the frequency of eating out and take-away meals. Data on dietary intake were collected using a one-day semi-weighed household dietary record. The inadequacy of each nutrient intake was assessed by comparing estimated average requirement (EAR) level for 14 nutrients and the range of the dietary goal (DG) for seven nutrients according to the 2015 version of the Dietary Reference Intake for Japanese. Participants were stratified into three groups based on the frequency of consuming home-cooked meals. Group differences in EAR and DG were assessed using the covariate and logistic regression analysis, respectively.Results: Among men and women, the proportion of participants who consumed home-cooked meals almost every day and meals prepared out of home at least once a day were 34.9% and 46.8%, and 14.7% and 6.3%, respectively. A higher frequency of consumption of home-cooked meals was associated with higher intake and adequacy of dietary fiber and minerals (iron, calcium, potassium etc.), and with higher intake of vegetables and lower intake of oils.Conclusions: Low frequency of home-cooked meal consumption was associated with insufficient intake of dietary fiber and multiple mineral intakes among Japanese adults. Dietary fiber and mineral intake may need to the focus of interventions aimed at improving nutrient intake in individuals who predominantly eat food prepared away from home.
Downregulation of miR-342-3p/miR-342-5p in type 1 diabetes mellitus and vascular health; Case controlled study in peripheral blood mononuclear cells and plasma, CD45dimCD34+CD133+ cells, inflammatory markers, CXCR1/2 and PANEX2 mRNA combined with Ingenuity Pathway Analysis
Authors: Ray Sabina L , Coulson David J , Yeoh Megan LY , Bakhashab Sherin , Tamara Alice , Latief Jevi S , Weaver Jolanta U
Published: May 2020

BACKGROUND Cardiovascular disease (CVD), the leading causes of death worldwide, correlates with inflammation and shortens life span in type 1 diabetes (T1DM). In animals, miR-342 were shown to be anti-inflammatory in CVD. We hypothesise: proangiogenic miR-342-3p/-5p are downregulated in T1DM whereas inflammatory cytokines are upregulated.METHODS We studied plasma/peripheral blood mononuclear cells (PBMCs) in 29 T1DM and 20 controls (HC). Vascular health was measured by Fibronectin Adhesion Assay (FAA), CD45 dim CD34 + 133 + cells (flow cytometry) and Tissue inhibitor of metalloproteases (TIMP-1). Inflammatory markers IL-7, IL-8, TNFα and VEGF-C were assayed by Mesoscale assay, mRNA for chemokine receptor CXCR1/2, PANX2 and miR 342-3p/5p by qRT-PCR. Analysis: Unpaired Student t test, Pearson correlation and Ingenuity Pathway Analysis (IPA) to predict miR-342-3p/-5p targets.RESULTS In T1DM, pro-inflammatory cytokines IL-8 and TNF-α, IL-7 and growth factor VEGF-C were increased versus HCs; p=0.008, p=0.003, p=0.041 and p=0.013 respectively. MiR-342-3p/-5p were downregulated in PBMCs in T1DM versus HC; p=0.01, but not in plasma. PANX2, CXCR1 and CXCR2 mRNA were increased in PBMCs in T1DM versus HCs; p=0.004, p=0.017 and p<0.001 respectively. MiR-342-3p correlated negatively with TIMP-1, IL-6, IL-8, TNF-α, HbA 1c ; p=0.006, p=0.031, p=0.029, p=0.038, p=0.001, p=0.031 whilst miR-342-5p with TIMP-1, IL-6, IL-8, HbA 1c , p=0.005, p=0.034, p=0.029, p=0.001, p=0.042 respectively. There was positive correlation between miR-342-3p and FAA, CXCR1, CXCR2; p=0.006, p=0.019, p=0.001 and between miR-342 - 5p and FAA, CXCR2; p=0.038, p=0.036 respectively. IPA predicted miR-342-3p/-5p to be anti-inflammatory through the indirect regulation of mitogen-activated protein 3 kinase 1, inhibitor of nuclear factor kappa B kinase regulatory subunit Gamma, Surfactant protein A1 and PANX2 as well as predicting IL-8, TNF-α, IL-7 and glucose to activate the inflammatory response. ROC curve analyses showed: miR-342-3p/-5p to be a biomarker for T1DM: p=0.01, p =0.006 respectively (2) significant downregulation of miR-342-3p/-5p has occured at HbA 1c > 46.45 mmol/mol, p=0.006, p =0.005 respectively.CONCLUSION Our findings validated animal studies. Downregulation of miR-342-3p/-5p by hyperglycaemia and increase in cytokines confirmed inflammation in T1DM. MiR-342-3p/5p correlated with indices of vascular health and defined early CVD at HbA1c of 46.5 mmol/mol cut off point. MiR-342-3p/-5p based either intervention or monitoring may prove to be beneficial in CVD in T1DM.
Ocular Manifestation of Elizabethkingia Meningoseptica
Authors: LEUNG KAI CHING PETER , KO TAK CHUEN SIMON
Published: May 2020

Background: Elizabethkingia is a Gram-negative, obligate aerobic, oxidase positive bacillus that is known to cause a variety of nosocomial infections and has emerged as an important pathogen because of multiple anti-microbial resistance. We present the largest case series of Elizabethkingia ophthalmic infections, with specific emphasis on its clinical spectrum, risk factors, treatment and outcome.Method: Microbiological specimens growing Elizabethkingia were reviewed retrospectively at a regional tertiary hospital from 2005-2019. Clinical manifestation, risk factors, treatment including types of antibiotics, treatment duration and clinical outcome were documented. Results: Ten cases of culture positive Elizabethkingia ophthalmic infection were identified, which all cultured E. meningoseptica. Four cases keratitis, three cases of conjunctivitis, two cases of blepharitis and one case blepharitis-conjunctivitis were observed. Four cases were found to be associated with contact lens use and were found to colonize E. meningoseptica. One case of blepharitis was associated with and ocular prosthesis (scleral shell) an eviscerated eye. Fluoroquinolone and chloramphenicol were most commonly used topical antibiotics for treatment. The mean treatment duration for all infections was averaged at 6.5 weeks. Conclusion: E. meningoseptica is found to be the predominant species that has caused infection at the ocular surface. Contact lens use and ocular prosthesis appears to be a risk factor for infection due to ocular surface barrier disruption and bacteria colonization. Combination of fluroquinolone and chloramphenicol is a safe and effective treatment against Elizabethkingia ocular infections. Further studies are required to determine the susceptibility of commonly used topical anti-microbial agents to Elizabethkingia species.
Differentiating novel coronavirus pneumonia from general pneumonia based on machine learning
Authors: Liu Chenglong , Wang Xiaoyang , Liu Chenbin , Sun Qingfeng , Peng Wenxian
Published: May 2020

Background
Chest CT screening as supplementary means is crucial in diagnosing novel coronavirus pneumonia (COVID-19) with high sensitivity and popularity. Machine learning was adept in discovering intricate structures from CT images and achieved expert-level performance in medical image analysis.
Methods
To develop and validate an integrated machine learning framework on chest CT images for differentiating COVID-19 from common pneumonia (CP). Seventy-three confirmed COVID-19 cases were consecutively enrolled together with twenty-seven confirmed common pneumonia patients from Ruian People’s Hospital, from January 2020 to March 2020. Statistical textual features of COVID-19 and CP images were extracted. After feature selection, the reserved features were applied to the ensemble of bagged tree (EBT) and four other machine learning classifiers with 10-fold cross-validation.
Results
The classification accuracy, precision, sensitivity, specificity and F1 score of our proposed method are 91.66%, 97.91%, 85.26%, 98.15% and 91.15% respectively. The AUC of its receiver operating characteristic is 0.98.
Conclusions
The experimental results indicate that the EBT algorithm with statistical textural features on chest CT for differentiating COVID-19 from common pneumonia achieved high transferability, efficiency, specificity, and impressive accuracy.
Etiological characteristic and risk factors of ESBL-Urinary Tract Infections: A nomogram had been built and Urologist should act in time
Authors: Wei Yi , Yu Chengjun , Zhao Tianxing , Lin Tao , He Dawei , Wu Sheng-de , Wei Guanghui
Published: May 2020

Background: The presence of urinary tract infection (UTI) due to Extended-Spectrum Beta-Lactamase (ESBL)-producing bacteria is reported increased. Aim to study the most frequent uropathogens and the antibiotic susceptibility patterns of them in children and identify whether urodynamic change, underlying neurologic disorders and undernourishment were independent risk factors for ESBL positive UTI which is unclear. Methods: We retrospectively reviewed microbial etiologies and antimicrobial resistance among patients experiencing UTI events in the urology ward of Chongqing Medical University Afflicated Chlidren's Hospital from January 1994 and December 2019. All strains were cultured and identified by the Clinical Microbiology Laboratory. Results: A total of 854 patients with UTI over a 26-years period were evaluated and Escherichia coli was the most common pathogen. During the study period, the proportion of UTI cases attributed to Enterococci increased significantly. Susceptibilities to carbapenems and amikacin decreased significantly, indicating increased antibiotic resistance of pathogens associated with UTI. Interestingly, the susceptibilities to piperacillin/tazobactam have increased. 72.64% were caused by ESBL bacteria and ESBL-producing bacteria increased significantly. ESBL (+) and ESBL (-) UTI were compared and there were no significant differences in the clinical presentation between gender, side of the lesion and urodynamic results. Significant potential risk factors of ESBL-UTI were presence of congenital urological abnormalities, vesicoureteral reflux, neurologic disorder, age <12months, fever and previous use of antibiotics in the last 3 months. On logistic regression analysis, underlying neurologic disorder (OR =8, CI 1.845-34.695) and history of previous antibiotics administration in the last 3 months (OR =4.764, CI 3.114-7.289) were identified as an independent significant risk factor for ESBL- UTI. The nomogram generated was well calibrated for all predictions of ESBL+ probability, and the accuracy of the model nomogram measured by Harrell’s C statistic (C-index) was 0.741. Conclusions: The current situation of multiple bacterial antibiotic resistance has become a worrisome issue in UTI, and urologist should act timely. Our data will greatly assist physicians recognizing the risk factors of ESBL-UTI and optimising antibiotic use.
Human development, social vulnerability and COVID-19 in Brazil: A study of the social determinants of health
Authors: de Souza Carlos Dornels Freire , Machado Michael Ferreira , Carmo Rodrigo Feliciano do
Published: May 2020

Background: COVID-19 was confirmed in Brazil in February 2020. Since then, the disease has spread throughout the country, reaching the poorest areas. This study analyzes the relationship between COVID-19 and the population’s living conditions. We aimed to identify social determinants related to the incidence, mortality, and case fatality rate of COVID-19 in Brazil, in 2020.Methods: This is an ecological study evaluating the relationship between incidence, mortality, and case fatality rates and 49 social indicators of human development and social vulnerability. For the analysis, bivariate spatial correlation and multivariate and spatial regression models (spatial lag model and spatial error models) were used, considering a 95% confidence interval and a significance level of 5%.Results: A total of 44.8% of municipalities registered confirmed cases of COVID-19 and 14.7% had deaths. We observed that 56.2% of municipalities with confirmed cases had very low human development (incidence: 59.00/100,000; mortality: 36.75/million), and 52.8% had very high vulnerability (incidence: 41.68/100,000; mortality: 27.46/million). The regression model showed 17 indicators associated with transmission of COVID-19 in Brazil.Conclusions: Although COVID-19 first arrived in the most developed and least vulnerable municipalities in Brazil, it has already reached locations that are farther from large urban centers, whose populations are exposed to a context of intense social vulnerability. Based on these findings, it is necessary to adopt measures that take local social aspects into account in order to contain the pandemic.
Relationship Between Clinical Control, Respiratory Symptoms and Quality of Life for Patients With Copd
Authors: Navarrete Bernardino Alcazar , Fuster A. , García-Sidro P. , García-Rivero J.L. , Bolado B. Abascal , Sanmartin A. Pallares , Martín E. Márquez , Valido-Morales A. , Boldova A. , Callejas-Gonzalez F.J. , Palop M. , Riesco J.A. , Golpe R. , Soler-Cataluña J.J. , Miravitlles M.
Published: May 2020

Background:The concept of clinical control has been proposed as an instrument for evaluating patients with COPD. However, the possible association between clinical control,reduced symptom severity and HRQoL has yet to be confirmed.Method: This multicentre, prospective and observational study was carried out in pulmonology clinics in Spain. The patients were followed up for six months, with a baseline visit (V0), followed by visits at three months (V1) and six months (V2). Clinical control was determinedat V1, with the application of both clinical criteria and the COPD assessment test (CAT). All patients reported their symptoms by a validated symptom diary (E-RS) using a portable device, and their HRQoL was assessed using the EQ5D questionnaire. The relationship between clinical control and E-RS andHRQoL during follow-up was assessed.Results: A total of126 patients were screened. After application of the inclusion/exclusion criteria, 93 were finally included (mean age 66 ± 8 years, 84.9% male), with a mean FEV1predicted of 49.8% ± 16.5%. Of these patients, 44 (47.3%) achieved clinical control at V1, according to CAT criteria, and 50 (53.8%), according to clinical criteria. The E-RS scores differed between controlled and uncontrolled patients at all time points, both according to CAT (mean differences of -4.6, -5.6 and -6.2 units at V0, V1 and V2 respectively, p<0.005 for all comparisons) and to clinical criteria (mean differences of -3.3, -5-6 and -4.99 units, respectively, p<0.005 for all comparisons). The controlled patients also presented a significantly better HRQoL, measured by the EQ5D questionnaire(mean difference 0.13and 0.10 at V2 by CAT or clinical criteria, respectively, p<0.05).Conclusions:Clinical control in patients with COPD, whether measured by CAT or by clinical criteria, is associated with a lower symptom load and a better HRQoL.