bluuebunny/crossref_metadata_2025_split huggingface dataset:
The longitudinal association of remnant cholesterol with cardiovascular outcomes in patients with diabetes and pre-diabetes
Authors: Cao Ye-Xuan , Zhang Hui-Wen , Jin Jing-Lu , Liu Hui-Hui , Zhang Yan , Gao Ying , Guo Yuan-Lin , Wu Na-Qiong , Hua Qi , Li Yan-Fang , Li Xiao-Lin , Xu Rui-Xia , Cui Chuan-Jue , Liu Geng , Dong Qian , Sun Jing , Zhu Cheng-Gang , Li Jian-Jun 
Published: July 2020

Abstract
Background
The atherogenicity of remnant cholesterol (RC) has been underlined by recent guidelines, which was linked to coronary artery disease (CAD), especially for patients with diabetes mellitus (DM). This study aimed to examine the prognostic value of plasma RC in the patients with CAD under different glucose metabolism status.

Methods
Fasting plasma RC were directly calculated or measured in 4331 patients with CAD. Patients were followed for the occurrence of major adverse cardiovascular events (MACEs) and categorized according to both glucose metabolism status [DM, pre-DM, normoglycemia (NG)] and RC levels. Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals.

Results
During a mean follow-up of 5.1 years, 541 (12.5%) MACEs occurred. The risk for MACEs was significantly higher in patients with elevated RC levels after adjustment for potential confounders. No significant difference in MACEs was observed between pre-DM and NG groups (p > 0.05). When stratified by combined status of glucose metabolism and RC, highest levels of calculated and measured RC were significant and independent predictors of developing MACEs in pre-DM (HR: 1.64 and 1.98; both p < 0.05) and DM (HR: 1.62 and 2.05; both p < 0.05). High RC levels were also positively associated with MACEs in patients with uncontrolled DM. .

Conclusions
In this large-scale and long-term follow-up cohort study, data firstly demonstrated that higher RC levels were significantly associated with the worse prognosis in DM and pre-DM patients with CAD, suggesting that RC may be a target for patients with impaired glucose metabolism.
Add-on therapy in metformin-treated patients with type 2 diabetes at moderate cardiovascular risk: a nationwide study
Authors: Thein David , Christiansen Mia Nielsen , Mogensen Ulrik Madvig , Bundgaard Johan Skov , Rørth Rasmus , Madelaire Christian , Fosbøl Emil Loldrup , Schou Morten , Torp-Pedersen Christian , Gislason Gunnar , Køber Lars , Kristensen Søren Lund 
Published: July 2020

Abstract
Background
In randomised clinical trials, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium–glucose cotransporter 2 (SGLT-2) inhibitors reduced cardiovascular events in patients with type 2 diabetes (T2D) at high cardiovascular risk, as compared to standard care. However, data comparing these agents in patients with T2D who are at moderate risk is sparse.

Methods
From Danish national registries, we included patients with T2D previously on metformin monotherapy, who started an additional glucose-lowering agent [GLP-1 RA, SGLT-2 inhibitor, dipeptidyl peptidase-4 (DPP-4) inhibitor, sulfonylurea (SU), or insulin] in the period 2010-2016. Patients with a history of cardiovascular events [heart failure (HF), myocardial infarction (MI) or stroke] were excluded. Patients were followed for up to 2 years. Cause-specific adjusted Cox regression models were used to compare the risk of hospitalisation for HF, a composite endpoint of major adverse cardiovascular events (MACE) (MI, stroke or cardiovascular death), and all-cause mortality for each add-on therapy. Patients who initiated DPP-4 inhibitors were used as reference.

Results
The study included 46,986 T2D patients with a median age of 61 years and of which 59% were male. The median duration of metformin monotherapy prior to study inclusion was 5.3 years. Add-on therapy was distributed as follows: 13,148 (28%) GLP-1 RAs, 2343 (5%) SGLT-2 inhibitors, 15,426 (33%) DPP-4 inhibitors, 8917 (19%) SUs, and 7152 (15%) insulin. During follow-up, 623 (1.3%, range 0.8-2.1%) patients were hospitalised for HF—hazard ratios (HR) were 1.11 (95% CI 0.89–1.39) for GLP-1 RA, 0.84 (0.52–1.36) for SGLT-2 inhibitors, 0.98 (0.77–1.26) for SU and 1.54 (1.25–1.91) for insulin. The composite MACE endpoint occurred in 1196 (2.5%, range 1.5–3.6%) patients, yielding HRs of 0.82 (0.69–0.97) for GLP-1 RAs, 0.79 (0.56–1.12) for SGLT-2 inhibitors, 1.22 (1.03–1.49) for SU and 1.23 (1.07–1.47) for insulin. 1865 (3.9%, range 1.9–9.0%) died from any cause during follow-up. HRs for all-cause mortality were 0.91 (0.78–1.05) for GLP-1 RAs, 0.79 (0.58–1.07) for SGLT-2 inhibitors, 1.13 (0.99–1.31) for SU and 2.33 (2.08–2.61) for insulin.

Conclusion
In a nationwide cohort of metformin-treated T2D patients and no history of cardiovascular events, the addition of either GLP-1 RA or SGLT-2 inhibitor to metformin treatment was associated with a similar risk of hospitalisation for HF and death, and a lower risk of MACE for GLP-1 RA when compared with add-on DPP-4 inhibitors. By contrast, initiation of treatment with SU and insulin were associated with a higher risk of MACE. Additionally, insulin was associated with an increased risk of all-cause mortality and hospitalisation for HF.
Comparative predictive ability of visit-to-visit HbA1c variability measures for microvascular disease risk in type 2 diabetes
Authors: Yang Chen-Yi , Su Pei-Fang , Hung Jo-Ying , Ou Huang-Tz , Kuo Shihchen 
Published: July 2020

Abstract
Background
To assess the associations of various HbA1c measures, including a single baseline HbA1c value, overall mean, yearly updated means, standard deviation (HbA1c-SD), coefficient of variation (HbA1c-CV), and HbA1c variability score (HVS), with microvascular disease (MVD) risk in patients with type 2 diabetes.

Methods
Linked data between National Cheng Kung University Hospital and Taiwan’s National Health Insurance Research Database were utilized to identify the study cohort. The primary outcome was the composite MVD events (retinopathy, nephropathy, or neuropathy) occurring during the study follow-up. Cox model analyses were performed to assess the associations between HbA1c measures and MVD risk, with adjustment for patients’ baseline HbA1c, demographics, comorbidities/complications, and treatments.

Results
In the models without adjustment for baseline HbA1c, all HbA1c variability and mean measures were significantly associated with MVD risk, except HVS. With adjustment for baseline HbA1c, HbA1c-CV had the strongest association with MVD risk. For every unit of increase in HbA1c-CV, the MVD risk significantly increased by 3.42- and 2.81-fold based on the models without and with adjustment for baseline HbA1c, respectively. The associations of HbA1c variability and mean measures with MVD risk in patients with baseline HbA1c < 7.5% (58 mmol/mol) were stronger compared with those in patients with baseline HbA1c ≥ 7.5% (58 mmol/mol).

Conclusions
HbA1c variability, especially HbA1c-CV, can supplement conventional baseline HbA1c measure for explaining MVD risk. HbA1c variability may play a greater role in MVD outcomes among patients with relatively optimal baseline glycemic control compared to those with relatively poor baseline glycemic control.
Prior bariatric surgery and perioperative cardiovascular outcomes following noncardiac surgery in patients with type 2 diabetes mellitus: hint from National Inpatient Sample Database
Authors: Jin Jiewen , Deng Zhantao , Xu Lijuan , Li Hai , Zhang Pengyuan , Liu Liehua , Liu Juan , Han Hedong , Huang Zhimin , Cao Xiaopei , Xiao Haipeng , Li Yanbing 
Published: July 2020

AbstractBackgroundBoth diabetes and obesity are risk factors for perioperative major adverse events. This study aims to evaluate the association between prior bariatric surgery (prior-BS) and perioperative cardiovascular outcomes following noncardiac surgery in patients with type 2 diabetes mellitus (T2DM).MethodsWe used the National Inpatient Sample Database to identify T2DM patients undergoing major noncardiac surgery from 2006 to 2014. The primary outcome was major perioperative adverse cardiovascular and cerebrovascular events (MACCEs), which include death, acute myocardial infarction and acute ischaemic stroke. In-hospital outcomes between patients with prior BS and morbid obesity were compared using unadjusted logistic, multivariable logistic and propensity score matching analyses.ResultsA weighted of 1,526,820 patients diagnosed with T2DM who underwent noncardiac surgery were included. The rates of both prior BS and morbid obesity significantly increased during the study period (P < 0.0001). Patients with prior BS were younger, were more likely to be female, and had lower rates of cardiovascular risk factors but had higher rates of smoking, alcohol abuse, anaemia, prior venous thromboembolism and prior percutaneous coronary intervention. The incidence of MACCEs was 1.01% and 3.25% in patients with prior BS and morbid obesity, respectively. After multivariable adjustment, we found that prior BS was associated with a reduced risk of MACCEs (odds ratio [OR] = 0.71; 95% confidence interval [CI] 0.62–0.81), death (OR = 0.64, 95% CI 0.52–0.78), acute kidney injury (OR = 0.66, 95% CI 0.62–0.70) and acute respiratory failure (OR: 0.46; 95% CI 0.42–0.50).ConclusionsPrior bariatric surgery in T2DM patients undergoing noncardiac surgery is associated with a lower risk of MACCEs. Prospective studies are needed to verify the benefits of bariatric surgery in patients undergoing noncardiac surgery.
BORA regulates cell proliferation and migration in bladder cancer
Authors: Cheng Songtao , Peng Tianchen , Zhu Xiaolu , Zhou Fenfang , Wang Gang , Ju Lingao , Xiao Yu , Liu Xuefeng , Wang Xinghuan 
Published: July 2020

Abstract
Background
Bladder cancer is having a gradually increasing incidence in China. Except for the traditional chemotherapy drugs, there are no emerging new drugs for almost 30 years in bladder cancer. New potential therapeutic targets and biomarkers are urgently needed.

Methods
BORA is the activator of kinase Aurora A and plays an important role in cell cycle progression. To investigate the function of BORA in BCa, we established BORA knockdown and overexpression cell models for in vitro studies, xenograft and pulmonary metastasis mouse models for in vivo studies.

Results
Our results indicated that BORA was upregulated in human bladder cancer (BCa) compared to the normal bladder and paracancerous tissues at transcriptional and translational levels. We found that BORA was positively related to BCa cell proliferation. Furthermore, BORA knockdown induced cell cycle arrest in G2/M phase while BORA overexpression decreased the proportion of cells in G2/M, associated with PLK1–CDC25C–CDK1 alteration. Interestingly, we observed that knockdown of BORA inhibited BCa cell migration and invasion, accompanied with alterations of epithelial–mesenchymal transition (EMT) pathway related proteins. In vivo studies confirmed the inhibition effect of BORA knockdown on BCa cell growth and migration.

Conclusions
Our study indicates that BORA regulates BCa cell cycle and growth, meanwhile influences cell motility by EMT, and could be a novel biomarker and potential therapeutic target in BCa.
Global health activists’ lessons on building social movements for Health for All
Authors: Musolino Connie , Baum Fran , Freeman Toby , Labonté Ronald , Bodini Chiara , Sanders David 
Published: July 2020

AbstractBackgroundThe People’s Health Movement (PHM) was formed in 2000 and drew inspiration from the Alma Ata Declaration on Primary Health Care’s ‘Health for All’ (1978). Since then PHM has been an active part of a global counter-hegemonic social movement. This study aimed to gain insights on social movement building, drawing on the successes and failures reported by activists over their experiences of working in the Health for All social movement to improve health, justice and equity.MethodsQualitative research methods were employed in this study to capture complex and historical narratives of individual activists, through semi-structured interviews and subsequent thematic analysis of transcripts. The research design and analysis were informed by social movement theory and literature on health activism as a pathway for social change. In this study we examine the semi-structured interviews of 15 health activists who are part of the PHM, with the aim of deriving lessons for strengthening movements for Health for All.ResultsThis study locates the activists’ narratives within a socio-political analysis of the global trends of late modern individualism and capitalist neoliberalism. This highlights the challenges faced by civil society groups mobilising collective action and building social movements for Health for All. The study found that within the constraints of the neoliberal socio-political and economic conditions which have caused the rise in social and health inequities, this group of long-term health activists have been nurturing alternative approaches to structuring society and building collective agency to improve health.ConclusionThe practical long-term experiences of the PHM activists examined in this study contribute to a better understanding of the processes and motivations that lead to and sustain health activism, and the dilemmas, strategies, impacts and achievements of such activism.
Improved diagnosis of pulmonary embolism causing cardiac arrest by combined endobronchial ultrasound and echocardiography
Authors: Bertini Pietro , Ribechini Alessandro , Guarracino Fabio 
Published: July 2020

Abstract
Background
Pulmonary embolism (PE) is a life-threatening disease difficult to diagnose and manage in severe hemodynamic unstable patients. Transoesophageal echocardiography (TEE) is considered useful to improve diagnosis, but such approach has physical limitations for the interposition of the airways preventing the clear assessment of the left pulmonary artery. Endobronchial ultrasound (EBUS), a recently developed technique carried out using a modified bronchoscope having a small ultrasound convex probe at the tip allowing to perform ultrasonography examination of the mediastinum, can extensively visualize the pulmonary arteries on both sides.

Case presentation
We present the first use of EBUS to rapidly diagnose and subsequently treat a 64 years old woman with history of lateral amyotrophic sclerosis admitted to the intensive care unit (ICU) for severe dyspnoea and rapidly experiencing a cardiac arrest.

Conclusions
Combined bedside EBUS and echocardiography allowed to rapidly diagnose the cause of cardiac arrest and avoid risks related to transferring the critical patient to the radiology department.
Renal Hemangioblastoma with Mixed Mullerian tumour of endometrium: A tale of two rare primary tumours
Authors: Setia Aparna , Kumar Devender , Bains Lovenish , Sharma Pallavi , Tempe Anjali , Mallya Varuna 
Published: July 2020

Abstract
Introduction
Renal hemangioblastoma (RH) is a very rare benign tumour. Hemangioblastoma most commonly occurs in the central nervous system (CNS), and only few cases of RH have been reported as they occur most commonly as asymptomatic masses found incidentally. Mixed Mullerian tumour (MMT) of the uterus is a rarer and aggressive form of uterine malignancy. The detection of two primary rare tumours incidentally is a rare entity.

Case presentation
A 50-year-old female presented with abnormal uterine bleeding which on endometrial sampling was diagnosed as a rare variety of endometrial cancer, i.e. MMT or uterine carcinosarcoma. On preoperative imaging, a renal mass was also detected which was highly vascular and was mimicking renal cell carcinoma (RCC). Fine needle aspiration cytology (FNAC) was done from the renal mass to differentiate between RCC and metastasis, but it showed only blood cells. Patient underwent staging laparotomy for endometrial cancer and frozen section examination of the renal mass which was inconclusive with few atypical cells, and thus, patient underwent radical nephrectomy too. Histopathological examination revealed it to be a RH which is a very rare benign tumour.

Discussion
RH is a rare benign tumour which does not require any treatment in majority of the patients. Only 26 cases of RH outside the CNS have been reported till date. MMT is a rare aggressive uterine tumour with an incidence of 1–2 % of all uterine neoplasms, which metastasizes early, and thus, early identification and treatment is the key. RH needs to be differentiated from RCC to avoid over treatment. Morphological findings are similar in RCC and RH; preoperative FNAC, PET scan, and intraoperative frozen section can be utilized to differentiate the two, in well-circumcised tumours and high index of suspicion. Occurrence of renal mass as an incidental finding in the preoperative work up of uterine malignancy directed us to the differentials of metastasis or another histologically distinct primary tumour. The presence of two rare primary tumours, i.e. RH and MMT in the same patient which are unrelated, is a rare entity.
The efficacy and safety of the addition of poly ADP-ribose polymerase (PARP) inhibitors to therapy for ovarian cancer: a systematic review and meta-analysis
Authors: Yang Yingzhu , Du Nannan , Xie Laidi , Jiang Jing , Mo Jiahang , Hong Jiaze , Mao Danyi , Ng Derry Minyao , Shi Huiwei 
Published: July 2020

Abstract
Background
The purpose of this study was to explore the efficacy and tolerability of poly ADP-ribose polymerase (PARP) inhibitors in patients with ovarian cancer.

Methods
The meta-analysis searched the PubMed, Web of Science, EBSCO, and Cochrane libraries from inception to February 2020 to identify relevant studies. And the main results of this study were long-term prognosis and treatment-related adverse events.

Results
The results showed that the addition of PARP inhibitors could significantly prolong progression-free survival (PFS) and overall survival (OS) for patients with ovarian cancer (HR 0.44, 95% CI 0.34–0.53, p < 0.001; HR, 0.79, 95% CI 0.65–0.94, p < 0.001, respectively). In the BRCA 1/2 mutation patients, the HR of PFS was 0.29 (p < 0.001), and the HR was 0.51 (p < 0.001) in the no BRCA 1/2 mutation patients. The HR of PFS was 0.40 (p < 0.001) in the homologous recombination deficiency (HRD) mutation patients, while the HR was 0.80 (p < 0.001) in the no HRD mutation patients. Moreover, the analysis found that the use of PARP inhibitors did not significantly increase the risk of all grade adverse events (AEs) (RR = 1.04, p = 0.16). But the incidence of grade 3 or higher AEs was increased (RR = 1.87, p = 0.002). In general, the AEs were mainly manifested in the blood system.

Conclusions
PARP inhibitors can improve the prognosis of ovarian cancer patients with and without genetic mutations (BRCA 1/2 or HRD). Furthermore, PARP inhibitors were tolerable to patients when added to their current therapy, although it inevitably adds the grade 3 and higher AEs.
Impact of the COVID-19 virus outbreak on movement and play behaviours of Canadian children and youth: a national survey
Authors: Moore Sarah A. , Faulkner Guy , Rhodes Ryan E. , Brussoni Mariana , Chulak-Bozzer Tala , Ferguson Leah J. , Mitra Raktim , O’Reilly Norm , Spence John C. , Vanderloo Leigh M. , Tremblay Mark S. 
Published: July 2020

Abstract
Background
Healthy childhood development is fostered through sufficient physical activity (PA; including time outdoors), limiting sedentary behaviours (SB), and adequate sleep; collectively known as movement behaviours. Though the COVID-19 virus outbreak has changed the daily lives of children and youth, it is unknown to what extent related restrictions may compromise the ability to play and meet movement behaviour recommendations. This secondary data analysis examined the immediate impacts of COVID-19 restrictions on movement and play behaviours in children and youth.

Methods
A national sample of Canadian parents (n = 1472) of children (5–11 years) or youth (12–17 years) (54% girls) completed an online survey that assessed immediate changes in child movement and play behaviours during the COVID-19 outbreak. Behaviours included PA and play, SB, and sleep. Family demographics and parental factors that may influence movement behaviours were assessed. Correlations between behaviours and demographic and parental factors were determined. For open-ended questions, word frequency distributions were reported.

Results
Only 4.8% (2.8% girls, 6.5% boys) of children and 0.6% (0.8% girls, 0.5% boys) of youth were meeting combined movement behaviour guidelines during COVID-19 restrictions. Children and youth had lower PA levels, less outside time, higher SB (including leisure screen time), and more sleep during the outbreak. Parental encouragement and support, parental engagement in PA, and family dog ownership were positively associated with healthy movement behaviours. Although families spent less time in PA and more time in SB, several parents reported adopting new hobbies or accessing new resources.

Conclusions
This study provides evidence of immediate collateral consequences of the COVID-19 outbreak, demonstrating an adverse impact on the movement and play behaviours of Canadian children and youth. These findings can guide efforts to preserve and promote child health during the COVID-19 outbreak and crisis recovery period, and to inform strategies to mitigate potential harm during future pandemics.
Pulmonary endothelium-derived PD-L1 induced by the H9N2 avian influenza virus inhibits the immune response of T cells
Authors: Zhang Qian , Mu Xiang , Dong Hong , Hu Ge , Zhang Tao , He Cheng , Siddique Naila 
Published: July 2020

Abstract
Background
The PD-1/PD-L1 pathway is an inhibitory signaling pathway that maintains the balance between the immune response and immunotolerance, and its overactivation in cancer and viral infections inhibits T cell function. The target cells of various viruses, microvascular endothelial cells (MECs) have been shown to be key regulatory points in immune regulation and virion diffusion in vivo during infection with multiple influenza virus subtypes. Furthermore, avian influenza virus (AIV) infection can induce immunosuppression by causing imbalances in immune responses and immune organ damage. Thus, the aim of this study was to investigate whether the H9N2 virus inhibited the immune function of T cells that migrated across MECs by upregulating PD-L1 expression on MECs.

Methods
The susceptibility of rat pulmonary microvascular endothelial cells (RPMECs) to the H9N2 virus was evaluated by a plaque-forming assay and immunofluorescence staining. Then, we quantified the mRNA and protein levels of PD-L1 in RPMECs induced by H9N2 virus infection using quantitative real-time PCR and flow cytometry. The interaction between the activated T cells and RPMECs infected with the H9N2 virus was revealed using a coculture system. The effect of endothelial-derived PD-L1 on T cell function was investigated by using ELISA and flow cytometry with or without a PD-L1-specific antibody.

Results
Surface staining and the plaque-forming assay showed that the H9N2 virus infected and replicated in RPMECs. Both the PD-L1 mRNA level and PD-L1 protein level were upregulated in RPMECs infected with the H9N2 virus. H9N2 virus-induced PD-L1 expression significantly reduced the secretions of IL-2, IFN-γ and granzyme B and perforin expression in T cells. The above data were significantly increased after treatment with an anti-PD-L1 antibody, confirming the above mentioned findings. In addition, the induction of PD-L1 expression decreased the proliferative capacity of the cocultured T cells but did not affect the apoptosis rate of T cells.

Conclusions
Taken together, the results suggest that the H9N2 virus is able to inhibit the T cell immune response by upregulating PD-L1 expression in pulmonary microvascular endothelial cells.