bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pyruvate anaplerosis is a mechanism of resistance to pharmacological glutaminase inhibition in Triple-receptor Negative Breast Cancer
Authors: Singleton Dean C , Dechaume Anne-Lise , Murray Pamela M , Katt William P , Baguley Bruce C , Leung Euphemia Y 
Published: April 2020

Abstract
Background Glutamine serves as an important nutrient with many cancer types displaying glutamine dependence. Following cellular uptake glutamine is converted to glutamate in a reaction catalysed by mitochondrial glutaminase. This glutamate has many uses, including acting as an anaplerotic substrate (via alpha-ketoglutarate) to replenish TCA cycle intermediates. CB-839 is a potent, selective, orally bioavailable inhibitor of glutaminase that has activity in Triple receptor-Negative Breast Cancer (TNBC) cell lines and evidence of efficacy in advanced TNBC patients. Methods A panel of eleven breast cancer cell lines was used to investigate the anti-proliferative effects of the glutaminase inhibitors CB-839 and BPTES in different types of culture medium, with or without additional pyruvate supplementation. The abundance of the TCA cycle intermediate fumarate was quantified as a measure if TCA cycle anaplerosis. Pyruvate secretion by TNBC cultures was then assessed with or without AZD3965, a monocarboxylate transporter 1 (MCT1) inhibitor. Finally, two dimensional (2D) monolayer and three dimensional (3D) spheroid assays were used to compare the effect of microenvironmental growth conditions on CB-839 activity.Results The anti-proliferative activity of CB-839 in a panel of breast cancer cell lines was similar to published reports, but with a major caveat; growth inhibition by CB-839 was strongly attenuated in culture medium containing pyruvate. This pyruvate-dependent attenuation was also observed with a related glutaminase inhibitor, BPTES. Studies demonstrated that exogenous pyruvate acted as an anaplerotic substrate preventing the decrease of fumarate in CB-839-treated conditions. Furthermore, endogenously produced pyruvate secreted by TNBC cell lines was able to act in a paracrine manner to significantly decrease the sensitivity of recipient cells to glutaminase inhibition. Suppression of pyruvate secretion using the MCT1 inhibitor AZD3965, antagonised this paracrine effect and increased CB-839 activity. Finally, CB-839 activity was significantly compromised in 3D compared with 2D TNBC culture models, suggesting that 3D microenvironmental features impair glutaminase inhibitor responsiveness. Conclusion This study highlights the potential influence that both circulating and tumour-derived pyruvate can have on glutaminase inhibitor efficacy. Furthermore, it highlights the benefits of 3D spheroid cultures to model the features of the tumour microenvironment and improve the in vitro investigation of cancer metabolism-targeted therapeutics.
Adolescent alcohol use in Estonia compared to that in Latvia, Lithuania, Finland, and Sweden: results from cross-sectional surveys, 2003–2015
Authors: Kudre Daisy , Vorobjov Sigrid , Pärna Kersti 
Published: April 2020

Abstract
Background: Patterns of alcohol use often start developing during adolescence and are associated with alcohol use and dependence during adulthood. The aims of the study were to describe trends in the prevalence of monthly alcohol use from 2003 to 2015 and to analyze the associations between alcohol use and family-related and school-related factors, risk behavioral factors and perceived alcohol availability in Estonia, Latvia, Lithuania, Finland, and Sweden.Methods: The study used nationally representative data of 15–16-year-old adolescents from the European School Survey Project on Alcohol and Other Drugs (ESPAD). Data from Estonia, Latvia, Lithuania, Finland, and Sweden collected in 2003, 2007, 2011, and 2015 were utilized (n=57,779). The prevalence of monthly alcohol use and light and strong alcohol use was calculated for each study year in all countries. A chi-square test for trend was used to evaluate statistically significant changes in alcohol use over the study period. Logistic regression analysis was performed to analyze the association between alcohol use and different factors. Fully adjusted odds ratios with 95% confidence intervals were calculated.Results: Monthly alcohol use decreased significantly among 15–16-year-old boys and girls in Estonia, Latvia, Lithuania, Finland, and Sweden from 2003 to 2015. In 2015, the prevalence of monthly alcohol use among boys was 36.1% in Estonia, 44.3% in Latvia, 32.4% in Lithuania, 32.3% in Finland, and 22.4% in Sweden, and among girls, it was 39.1%, 45.9%, 35.6%, 31.8%, and 29.1%, respectively. In Estonia, Latvia, Lithuania, and Sweden, girls had higher odds of monthly alcohol use than boys. In all countries, higher odds of monthly alcohol use were observed among adolescents who skipped school, smoked cigarettes, used cannabis, perceived alcohol to be easy to access and had parents who did not know always/often about their child’s whereabouts on Saturday nights.Conclusion: From 2003 to 2015, monthly alcohol use decreased in Estonia as well as in neighboring countries such as Latvia, Lithuania, Finland, and Sweden. The factors related to alcohol use in all five countries were generally similar. Based on the study results, health promotion and alcohol policy interventions could be improved to decrease and prevent alcohol use among adolescents.
Co-infected with trichomonas vaginitis increases the risk of CIN2-3 among HPV16 positive female: a large population-based study
Authors: Yang Mei , Li Lin , Jiang Chunfan , Qin Xiaomin , Zhou Min , Mao Xiaogang , Xing Hui 
Published: April 2020

Abstract
Background: Evidences suggested that the vaginal microbiome played a functional role in the progression of cervical lesions in female infected by HPV. This study aimed at evaluating the influence of common vaginal infection on the carcinogenicity of hr-HPV.Methods: From January 15, 2017 to December 31, 2017, 310,545 female aged at least 30 years old had been recruited for cervical cancer screening from 9 clinical research centers in Central China. All the recruited participants received cervical cancer screening and vaginal microenvironment test by a high vaginal swab. Colposcopy-directed biopsy was recommended for female who were infected with HPV 16 and HPV 18 and other positive hr-HPV types through test had undertaken triage using liquid-based cytology, cases with the results ≥ ASCUS among them were referred to colposcopy directly.Results: Among 310,545 female, 6,067 (1.95%) were tested with positive HPV 16 and HPV 18, 18,297 (5.89%) were tested with other positive hr-HPV genotypes, cervical intraepithelial neoplasia (CIN) 1, CIN 2, CIN 3 and invasive cervical cancer (ICC) were detected in 861 cases, 377 cases, 423 cases and 77 cases, respectively. Candida albicans and Gardnerella were not associated with the progression of cervical lesions. Positive trichomonas vaginitis (TV) was correlated with hr-HPV infection (p<0.0001). Co-infection with TV increased the risk of CIN 1 among female infected with hr-HPV (OR 1.18, 95% CI: 1.42-2.31). Coinfection with TV increased the risk of CIN 2-3 among female infected with HPV 16 (OR 1.71, 95% CI: 1.16-2.53).Conclusions: Co-infection of TV and HPV 16 is an important risk factor for the progression of cervical lesions.
The Prevalence of Mental Health Problems and Associated Risk Factors among Military Health Workers of COVID-19 Specialized Hospitals in Wuhan, China: A Cross-Sectional Survey
Authors: Pan Xiao , Xiao Ying , Ren Ding , Xu Zhengmei , Zhang Qian , Yang Liying , Liu Fen , Hao Yushi , Bai Yonghai , Zhao Feng 
Published: April 2020

Abstract
Background China has been severely affected by COVID-19 (Coronavirus Disease 2019) since December 2019.In the combat against COVID-19, military health workers in China suffered from many pressures. This study aimed to investigate the current psychological status and risk factors of the military health workers.Methods Using a web-based cross-sectional survey, we collected data from 194 military health workers from three inpatient wards in two COVID-19 specialized hospitals. The survey questions consisted of demographic information, Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-15 (PHQ-15). Hierarchical regression analysis was used to explore potential risk factors for mental health problem.Results The overall prevalence of depressive symptoms, generalized anxiety and somatic symptoms were37.6%, 32.5% and 50%, respectively. Severe depression, generalized anxiety and somatic symptoms was 5.2%, 3.6% and 15.5%. In 22.7% of cases, comorbidities existed between depression, generalized anxiety and somatization. Junior-grade professional title was associated with depression, older age was associated with generalized anxiety and somatization, and less sleep duration and poor sleep quality were associated with all three symptoms.Conclusion The prevalence of depression, generalized anxiety and somatic symptoms were high in military health workers of COVID-19 specialized hospitals during the COVID-19 outbreak. Junior-grade professional title, older age, less sleep duration, and poor sleep quality have significant effects on the mental health of military health workers. Continuous surveillance and monitoring of the psychological consequences of the COVID-19outbreak should become routine to promote the mental health of military health workers.
Taohong Siwu (TSW) decoction enhances angiogenesis by regulation of VHL/HIF-1α/VEGF pathway
Authors: Tang Zhi , Li Wangyang , Xie Hongzan , Jiang Shengping , Pu Yunqing , Xiong Hui 
Published: April 2020

Abstract
Background: The incidence of bone fracture and bone-related diseases is increasing year by year. Angiogenesis plays vital role in fracture healing and bone repair. In this study, we assessed the effect of Taohong Siwu (TSW) decoction on angiogenesis by treatment of isolated rat aortic endothelial cell with TSW-containing serum. Method: First, TSW-containing serum was prepared from male Sprague-Dawley by intragastrically administration of TSW decoction. Then, isolated aortic endothelial cells were treated with different dose of TSW-containing serum. The effect of TSW-containing serum on the viability/proliferation of aortic endothelial cells were examined by MTT assay. The effects of TSW-containing serum on endothelial cell invasion, migration/spreading were detected by trans-well assay and scratch/wound-healing assay respectively. In addition, the effect of HIF-1α inhibitor on TSW-induced cell invasion and migration was also assessed. Moreover, the effect of TSW-containing serum on the expression of HIF-1α signaling pathway related protein, including HIF-1α, VHL and VEGF was detected by qRT-PCR and western-blot. Results: Our results showed that TSW decoction significantly increased the endothelial viability, invasion and wound-healing in a dose-dependent manner. Importantly, these enhanced effects induced by TSW were attenuated by HIF-1α inhibitor. Furthermore, our data demonstrated that TSW-containing serum increased the expression of HIF-1α and VEGF in a dose-dependent manner, while decreased the expression of VHL slightly. These effects induced by TSW were reversed by HIF-1α inhibitor. Conclusion: In summary these results for the first time suggested that TSW decoction enhances the angiogenesis by regulating of VHL/HIF-1α/VEGF pathway.
Tanshinone IIA Attenuates Inflammatory Responses by Downregulating MicroRNA-23b, Upregulating TRIB1 and Inactivation of the TLR4/NF-κB Signaling Pathway in THP-1 Macrophages
Authors: Ji Wei , Li Gengyao , Liu Yuqian , Yan Xiaofeng 
Published: April 2020

Abstract
Background: Atherosclerosis is a kind of chronic cardiovascular disease, and Tanshinone IIA (Tan) is a naturally derived anti-inflammatory compound. In this study, we aim to explore the biological role of Tan and regulatory mechanism in atherosclerosis.Methods: Firstly, the model of atherosclerosis mice was constructed. The area of atherosclerosis, the level of blood lipid and the content of inflammatory factors were measured in mice treated with Tan. After that, the differentially expressed microRNAs (miRNAs) were obtained by microarray analysis of mice plasma. The effect of miR-23b on cell migration ability, adhesion ability and inflammatory factor level of macrophages treated with Tan. After that, we determined the target mRNA of miR-23b through the bioinformatics analysis and the dual luciferase reporter gene assay. THP-1 macrophages were treated with miR-23b mimic or si-TRIB1 to detect the activity of the TLR4/NF-κB signaling pathway via immunohistochemistry.Results: Tan injection significantly improved atherosclerosis inflammation in mice, especially in mice treated with 90 mg/kg dose. miR-23b was obtained by differential screening, which can significantly inhibit the drug effect of Tan, and aggravate the occurrence of atherosclerosis. miR-23b targeted TRIB1, the decrease of TRIB1 also inhibited the drug effect of Tan. The up regulation of miR-23b enhanced the activity of TLR4/NF-κB pathway, and TLR4/NF-κB pathway inhibited the drug effect of Tan on the inflammatory response.Conclusion: Overall, Tan could protect macrophage against inflammation via inactivating TLR4/NF-κB pathway by down-regulating miR-23b and upregulating TRIB1, providing a novel theoretical foundation for treatment of atherosclerosis.
Management of chlamydia and gonorrhoea infections diagnosed in primary care using a centralised nurse-led telephone-based service: mixed methods evaluation
Authors: Brangan Emer , Horwood Jeremy , Manley Petra , Horner Paddy , Muir Peter , North Paul , MacLeod John 
Published: April 2020

Abstract
Background
Up to 18% of genital Chlamydia infections and 9% of Gonorrhoea infections in England are diagnosed in Primary Care. Evidence suggests that a substantial proportion of these cases are not managed appropriately in line with national guidelines. With the increase in sexually transmitted infections and the emergence of antimicrobial resistance, their timely and appropriate treatment is a priority. We investigated feasibility and acceptability of extending the National Chlamydia Screening Programme’s centralised, nurse-led, telephone management (NLTM) as an option for management of all cases of chlamydia and gonorrhoea diagnosed in Primary Care.
Methods
Randomised feasibility trial in 11 practices in Bristol with nested qualitative study. In intervention practices patients and health care providers (HCPs) had the option of choosing NLTM or usual care for all patients tested for Chlamydia and Gonorrhoea. In control practices patients received usual care.
Results
1154 Chlamydia/gonorrhoea tests took place during the 6-month study, with a chlamydia positivity rate of 2.6% and gonorrhoea positivity rate of 0.8%. The NLTM managed 335 patients. Interviews were conducted with sixteen HCPs (11 GPs, 5 nurses) and 12 patients (8 female). HCPs were positive about the NLTM, welcomed the partner notification service, though requested more timely feedback on the management of their patients. Explaining the NLTM to patients didn’t negatively impact on consultations. Patients found the NLTM acceptable, more convenient and provided greater anonymity than usual care. Patients appreciated getting a text message regarding a negative result and valued talking to a sexual health specialist about positive results.
Conclusion
Extension of this established NLTM intervention to a greater proportion of patients was both feasible and acceptable to both patients and HCP, could provide a better service for patients, whilst decreasing primacy care workload. The study provides evidence to support the wider implementation of this NLTM approach to managing chlamydia and gonorrhoea diagnosed in primary care.
Cataract risk had a positive association with metabolic syndrome and negative with a traditional balanced diet in middle-aged adults
Authors: Jee Dong Hyun , Park Sunmin 
Published: April 2020

Abstract
Background

The prevalence of cataracts is steadily increasing among middle-aged and elderly Asians. We hypothesized that adults aged 40–77 years with cataracts would show an association with metabolic syndrome and its components and have different dietary patterns and lifestyles.
Methods

The study was performed using the Korean genome and epidemiology study (KoGES; a large-scale hospital-based cohort study) data collected during 2004–2013. Subjects were classified as cases(945 cataract patients) and controls(27,454 healthy controls) based on responses to the question "have you ever been diagnosed to have a cataract?”.
Results

The presence of metabolic syndrome had a significant positive association with cataract risk after adjusting for age, sex, resistance area, BMI and energy intake(model 1; by 1.23-fold) and socioeconomic parameters(model 2; 1.15-fold). Plasma glucose and HbA1c concentrations also exhibited a higher cataract risk by 1.92- and 2.07-fold, respectively. For the analysis we used four dietary patterns to represent Korean food intake, that is, a traditional balanced diet, a meat and fish diet, a bread and cookie diet, and a grain-based diet. High traditional balanced diet consumption had a negative association with cataract risk(OR = 0.84), but high grain-based diet consumption exhibited a positive association with cataract risk(OR = 1.41). Systolic blood pressure and high carbohydrate intake(OR = 1.42) were also associated with cataract risk in model 1, but high fat and protein intake showed negative associations(OR = 0.74 and 0.74, respectively).
Conclusions

The risk of cataract development was found to be positively associated with metabolic syndrome, high systolic blood pressure, and hyperglycemia and negatively associated with a traditional balanced diet.
Is Lutikizumab, an Anti–Interleukin-1α/β Dual Variable Domain Immunoglobulin, efficacious for Osteoarthritis? Results from a bayesian network meta-analysis
Authors: Cao Ziqin , Hu Xutao , Zhou Jian , Wu Tong , Aili Dilihumaer , Long Zeling , Li Yihan , Sun Jingjing , Wang Wanchun , Wu Ren 
Published: April 2020

Abstract
OBJECTIVEOsteoarthritis (OA) is the most common form of joint disease which usually affects load-bearing joints such as hip and knee joints. Most guidelines recommend the use non-steroidal anti-inflammatory drugs (NSAIDs), duloxetine and tramadol for the non-operative treatment of OA, the use of them is limited by the tolerability and safety concerns. Lutikizumab is a novel anti–IL-1α/β dual variable domain immunoglobulin that can simultaneously binds and inhibits IL-1α and IL-1β to relieve the pain and dysfunction symptoms. We conducted this network meta-analysis to comprehensively compare the clinical efficacy and safety of lutikizumab with other drugs recommended by guidelines.DESIGNSystematic review and Bayesian network meta-analysis.DATA SOURCESAll eligible studies in PubMed, CKNI, EMBASE and Web of Science databases, from January 2000 to January 2020.METHODSBayesian network and conventional meta-analyses were conducted. Pain relief, function improvement and risk of adverse effects (AEs) were assessed.RESULTS24 articles with 11858 patients were included. Lutikizumab showed no benifit compared with placebo for both pain relief (SMD 1.11, 95% CI [-2.29 to 4.52]) and function improvement (SMD 0.992, 95% CI [-0.433 to 4.25]). Lutikizumab and all other drugs are of favorable tolerance for patients in treatment of OA compared with placebo.CONCLUSIONSThe results show that lutikizumab, the new anti–Interleukin-1α/β dual variable domain immunoglobulin, did not improve pain or function in the comparison with placebo. Selective cox-2 inhibitors remain the most effective and safest treatment for osteoarthritis. More high-quality trials are still needed to reconfirm the findings of this study.
The implementation of the nationwide out of hours phone number 1733. Analysis of efficiency and safety.
Authors: Delmeiren Lukas , Pietermans Sjors , Janssens Marco , Mullen Crhis Van Der , Sabbe Marc , Schoenmakers Birgitte 
Published: April 2020

Abstract
Background In Belgium there is a problem with improper use of emergency services. The government installed an emergency number 1733 for out of hours care. Through a dry run test we learned that 10% of all calls were allocated to the protocol ‘unclear problem’. In only 10% of all cases, there was indeed an unclear problem.Methods This study aimed to determine whether the adjusted protocol ‘unwell for no clear reason’ led to a safer and more efficient referral and to evaluate the efficiency and safety of the specific primary care protocols. The study was performed in a retrospective and prospective design and involved the community, patients, General Practitioner Cooperatives, emergency departments and telephone operators.Results During 6 months in 2018, 11622 calls to 1733 were registered. 756 of these calls were allocated to ‘unwell for no clear reason’. A random sample of 180 calls was re-listened. The efficiency and safety of the protocol ‘unwell for no clear reason’ improved. The safety levels for under- and over-triage were not exceeded. The GP’s on duty judged that 9/10 of all patient encounters were correctly allocated. In less than 1% of all referrals, there was an under-triage.Conclusion This study demonstrated that the implementation of a 1733-operating system to triage patients to an adequate care level is successful if protocols, flow charts and care levels are well defined and operators well trained.
Factors related to COVID-19 severity and mortality based on comparison between Henan and Zhejiang: an observational study
Authors: Ji Wangquan , Liang Ruonan , Zhu Peiyu , Yang Haiyan , Chen Shuaiyin , Zhang Weiguo , Jin Yuefei , Duan Guangcai 
Published: April 2020

Abstract
Background: Coronavirus Disease 2019 (COVID-19) has spread across China and the world, since outbreak at the end of 2019. Although COVID-19 is generally considered as self-limiting, some of cases develop in to fatal respiratory restress, multiple organ failure and even sudden death. According to the data released by the provincial health commissions, there are obvious regional differences in COVID-19 mortality. To explore possible factors of COVID-19 related severity and mortality in laboratory-confirmed cases from Henan and Zhejiang.Methods: We collected the public data released by the government. We analyzed and compared the possible factors, including initial symptoms, gender, age, place of residence, time interval from onset to diagnosis, epidemiological history and the grade of hospital for patient’s treatment in laboratory-confirmed cases. Student’s t-test, Chi-square (c2) test, Cochran-Mantel-Haenszel (CMH) test and Mann-Whitney U rank sum test were used complied with the applicable conditions. Statistical test was performed with a level of significance α=0.05.Results: Death cases in Henan were mainly from male, elderly infected persons and those who had a history of contact with patients and underlying basic diseases. Henan had the higher proportion of cases with fever and the lower proportion of asymptomatic infection, and had higher proportions of imported male cases with a contact history, and elderly cases living in rural areas, relative to Zhejiang. The time interval of confirmed cases in rural areas of Henan was 0.8 day longer than that in Zhejiang. Hospitals grade for patients’ treatment in Henan was lower than Zhejiang.Conclusions: Our findings suggest that initial symptoms, age, place of residence, gender, the time interval from onset to diagnosis and the grade of designated hospital for patient’s treatment are possible factors behind COVID-19 related severity or mortality. This study will provide useful information for public health authorities to develop disease prevention strategies.