bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subgroup Analysis in Pulmonary Hypertension-specific Therapy Trials: a Systematic Review
Authors: Rodríguez-Ramallo H , Báez-Gutiérrez N , Candelera R Otero , Flores-Moreno S , Martín L Abdel-kader 
Published: September 2021

Abstract
Background. Pulmonary hypertension (PH) treatment decisions are driven by randomized controlled trials (RCTs) results. Subgroup analyses are often performed to assess whether the intervention effect will change due to the patient’s characteristics. As subgroup claims may mislead clinician treatment decisions, there is a need for standards of such analyses.Objective. To evaluate the appropriateness and interpretation of subgroup analysis performed in pulmonary hypertension-specific therapy RCTs.Methods. A systematic review of the literature for pulmonary hypertension-specific therapy RCTs published between January 2000 and December 2020 was conducted. Claims of subgroup effects were evaluated with Sun X et al., 2012 criteria.Results. 30 RCTs were included. Evaluated subgroup analyses presented: a high number of subgroup analyses reported, lack of prespecification, and interaction test. The trial protocol was not available for most RCTs; significant differences were found in those articles which published the protocol. Authors reported 13 claims of subgroup effect, with 12 claims meeting 4 or fewer Sun criteria. Conclusion. Subgroup analyses in pulmonary hypertension-specific therapies are of poor quality. The lack of published protocols limited our capability to assess whether the published results correspond to the initially predefined analyses. Most claims of subgroup effect did not meet critical criteria.
Choice of Antithrombotic Therapy for Patients with Atrial Fibrillation Undergoing Carotid Angioplasty and Stenting: A Nationwide Population-Based Study
Authors: Huang Yung-Chuan , Huang Yen-Chun , Cheng Yu-Chen , Chen Mingchih 
Published: September 2021

Abstract
Non-valvular atrial fibrillation (NVAF) and carotid stenosis are important risk factors for stroke. Carotid angioplasty and stent placement (CAS) is recommended for patients with symptomatic high-grade carotid stenosis. The optimal medical management for patients with NVAF after CAS remains unclear. We aimed to clarify this issue using real-world data from the Taiwanese National Health Insurance Research Database (NHIRD). A total of 2116 NVAF patients who received CAS between January 1, 2010, and December 31, 2016, from NHIRD were divided into groups based on post-procedure medication as follows: only antiplatelet agent (OAP, n = 587); only anticoagulation agent (OAC, n = 477); dual antiplatelet agents (DAP, n = 49); and a combination of antiplatelet and anticoagulation agents (CAPAC, n = 304). Mortality, vascular events, and major bleeding episodes were compared after matching with the Charlson comorbidity index and CHA2DS2-VASc score. The CAPAC and the OAC groups had lower mortality rates than the OAP group (P = 0.0219), with no statistical differences in major bleeding, ischemic stroke, or vascular events. In conclusion, OAC therapy after CAS appears suitable for NVAF patients. CAPAC therapy might be considered as initial therapy or when there is concern about vascular events.
PNU-74654 enhanced the antiproliferative activity of gemcitabine via targeting Wnt/β-catenin Pathway in Pancreatic cancer
Authors: Sharifi Sajjad , Rahmani Farzad , Nosrati-Tirkani Abolfazl , Mehrabadi Shima , Fiuji Hamid , Khazaei Majid , Hassanian Seyed Mahdi , Rajabian Majid , Boromand Nadia , Parizade Seyed Mohammad Reza , Ferns Gordon A , avan Amir 
Published: September 2021

Abstract
Background : The Wnt/beta-catenin pathway is dysregulated in pancreatic cancer and is reported to be associated with poor prognosis, indicating the need for identification of novel agents to improve the efficacy of current therapy or have better activity. Therefore in the present study we explored the anticancer activity of PNU-74654 alone or in combination with gemcitabine in 2 and 3 dimensional cell culture model of pancreatic cancer. Methods: The MTT assay was applied to determine the viability of PC cancerous cells (PCC), while the cytotoxicity of this agent was evaluated in 3D cell culture model (spheroid). The effects of PNU-74654 was investigated in established cell migration/invasion assays. Result: The expression of candidate genes affecting the cell cycle, migration, and Wnt/b-catenin pathway was evaluated at mRNA and/or proteins by RT-PCR or Western blot. PNU-74654 inhibited the cell growth at IC50 of 122±0.4 umol/L, and had a synergistic effect on the antiproliferative properties of gemcitabine by modulating the Wnt pathway. The PNU-74654/gemcitabine combination reduced the migratory and invasiveness of PC cells, compared to control cells through perturbation of E-cadherin. Conclusion: In aggregate our findings demonstrated the profound antitumor properties of PNU-74654 in pancreatic cancer, supporting further studies to evaluate the therapeutic impact of this novel therapy to target Wnt pathway in the treatment of pancreatic cancer.
Dolutegravir Reported Adverse Drug Reactions: A Systematic Review Protocol
Authors: Wadesango Lesley , Wiafe Ebenezer , Padayachee Neelaveni , Mensah Kofi , Bangalee Varsha 
Published: September 2021

Abstract
Background: Until recently, the first-line regimen for the management of Human Immunodeficiency Virus (HIV) was Tenofovir (TDF)-Emtricitabine (FTC) and Efavirenz (EFV). However, the use of EFV has now been limited due to adverse neurosensory effects and a low genetic barrier to resistance. This regimen has been replaced by the Dolutegravir (DTG)-based regimen since DTG has a high genetic barrier to resistance. Studies have reported a higher risk of Immune Reconstitution Inflammatory Syndrome (IRIS), weight gain, insomnia, and neural tube defects amongst people who received DTG. This review aims to assess the adverse drug reaction (ADR) profile of Dolutegravir by identifying and classifying Dolutegravir-associated adverse drug reactions.Methods: Studies will be identified from an electronic database search. Studies that are potentially eligible will be selected through screening. Two team members will independently screen all citations, full-text articles, and abstract data; conflicts will be resolved through discussion. The (PRISMA-P) flow diagram that outlines all phases of screening and reasons for exclusion will be used during the selection process. After the selection of the final study sample, a data extraction form will be used as a collection tool. The data will be entered into Cochrane Collaboration Review Manager (RevMan 5.2) for storage and management. All the evidence gathered will be assessed for bias through the use of the Risk of Bias tool RoB 2.0 of Cochrane Collaboration. Reported ADRs will then be classified. We will also provide data for the effect of different demographic factors on ADRs as well as the effects of co-administration of DTG with other drugs on ADRs. We will additionally provide information on how Dolutegravir use in different regimens affects the ADRs. Results from the review will be summarized quantitatively through meta-analysis. A forest plot will be used to present results from the meta-analysis. Conclusion: A review of existing studies will aid in establishing the safety profile of this drug. This review will make significant contributions to healthcare practice. It will aid in improving prescribers' and dispensers’ knowledge of the drug. Additionally, it will also aid in patient education of the potential ADRs to DTG.Systematic review registration DOI: doi.org/10.17605/OSF.IO/Z9YAF
Effectiveness of Person-centred Integrated Care for Community-dwelling People With Hypertension and Diabetes in High-income Countries: Protocol for a Systematic Review and Meta-analysis
Authors: Tu Qiang , Xiao Lily , Hyun Karice , Lin Shuanglan , Fuller Jeffrey , Hafiz Nashid , Mohammadi Leila , Redfern Julie 
Published: September 2021

Abstract
Background: Hypertension and diabetes are two of the high prevalent non-communicable diseases. Inadequate care coordination among health systems and between health professionals as well as limited self-care capability of patients lead to the suboptimal care for people with hypertension and diabetes. Person-centred integrated care aiming to address these three levels of barriers has been proposed by World Health Organization as a global strategy to enhance the quality of care for people with chronic diseases. However, the effectiveness and characteristics of integrated care for community-dwelling people with hypertension and diabetes has not been systematically assessed.Methods: A systematic literature search will be conducted in seven databases including MEDLINE, Emcare, CINAHL, EMBASE, Cochrane Library of systematic reviews, Scopus and ProQuest. Additional studies will be identified through manual searching of reference lists and grey literatures. Quantitative studies (e.g. randomized controlled trials, quasi-randomized trials, before-and-after studies) evaluating the effects of integrated care for community-dwelling people with hypertension and diabetes will be included. Primary outcomes will be systolic and diastolic blood pressure. Secondary outcomes will include the proportion of patients achieving target blood pressure, glycated haemoglobin, fasting blood glucose, blood lipid, treatment adherence, health knowledge, mortality, quality of life, hospitalisation, emergency department use, patient satisfaction, adverse events and caregiver burden. Two reviewers will independently screen articles, extract data and assess study quality. Methodological quality of the selected studies will be assessed using the Revised Cochrane risk-of-bias tool and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Disagreements will be resolved through team discussion. Random effects model will be used for data synthesis if feasible.Discussion: This systematic review will summarise the evidence regarding the overall effectiveness, core components and implementation mechanism of integrated care interventions for people with hypertension and diabetes. Findings from the review will provide crucial evidence to inform the development of health policy, clinical practice and health resources to relieve the burden of hypertension and diabetes on healthcare systems.Registration: The protocol is registered with PROSPERO (registration number CRD42021271338)
Rock2 Regulates Proliferation and Differentiation of Chondrocytes in Osteoarthritis through β-catenin Signaling
Authors: Hao Liang , Chen Jun , Shang Xiliang , Yang Wu , Chen Shiyi 
Published: September 2021

Abstract
BackgroundOsteoarthritis (OA) adversely affects quality of life of elderly patients and is among hotspots and challenges of current research efforts. However, mechanism of occurrence and development of OA has not been fully elucidated. MethodsThrough qRT-PCR and Western blot assays, the current study established that levels of Rock2, a key protein in Rho signaling pathway, were significantly higher in OA cartilage. Furthermore, the current study explored effect of down-regulating Rock2 expression on growth and apoptosis of cartilage cells using CCK-8, Edu and Flow cytometry assays. Alkaline phosphatase (ALP) and Alizarin Red S (ARS) assays were then used to determine differentiation effects.ResultsFindings showed that expression of Rock2 is closely related to proliferation, apoptosis and differentiation of chondrocytes. Furthermore, the current study confirmed that Rock2 affects growth and differentiation of chondrocytes by activating β-catenin signaling pathway. Conclusionthe current study provided novel insights to targeted therapy of OA.
Spatial Heterogeneity Analysis of Soil Heavy Metals in Chongqing City Based on Different Interpolation Methods
Authors: Chen Wende , Cai Yankun , Wei Jun , Zhu Kun 
Published: September 2021

Abstract
Heavy metal pollution in urban soil is an important indicator of environmental pollution, which is of great significance to the sustainable development of cities. Choosing the best interpolation method can accurately reflect the distribution characteristics and pollution characteristics of heavy metals in soil, which is conducive to effective management and implementation of protection strategies. In this study, the grid sampling with a depth of 40cm was carried out in the whole study area based on the principle of uniform sampling, and the characteristics of As, Cu and Mn elements in the soil of the main urban area of Chongqing were investigated. The interpolation accuracy and difference of results of four interpolation methods, namely ordinary Kriging (OK), inverse distance weighting (IDW), local polynomial (LPI) and radial basis function (RBF), were analyzed and compared. The results showed that the average values of As (5.802 mg kg-1), Cu (23.992 mg kg-1) and Mn (573.316 mg kg-1) in the soil of the study area were lower than the background values of heavy metals in Chongqing. Coefficient of variation showed that As (55.71%), Cu (35.73%) and Mn (32.21%) all belonged to moderate variation. The parameters of semi-variance function theory model show that Cu element belongs to moderate spatial correlation, and As and Mn element have strong spatial correlation. The spatial distribution of the three elements was further predicted by using OK method, IDW method, LPI method and RBF method, which showed that LPI and OK method had strong smoothing effect and could not reflect the information of local point source pollution, while the interpolation results of IDW method and RBF method greatly retained the maximum and minimum information of element content, which reflected the necessity of using different methods when studying the spatial distribution of soil properties.
Evaluation of Indonesian Anti-obesity Traditional Medicinal Plants: A Systematic Review and Meta-analysis on Pancreatic Lipase Inhibition Activity
Authors: Hasim Hasim , Faridah Didah Nur , Afandi Frendy Ahmad , Qomaliyah Eka Nurul 
Published: September 2021

Abstract
BackgroundResearches and publication discussing performance of medicinal plants as anti-obesity have proliferated in recent years. In the view of ethnopharmacology, empiric evidence of Indonesian medicinal plants in management of obesity is widely accepted. In attempt to find anti-obesity agent, it is evidenced that the disorder can be resolved through inhibition of pancreatic lipase since the mechanism allowed to retard absorption of fat into cells. This current work aimed to screen Indonesian medicinal plants by using ethnopharmacology and meta-analysis approaches, emphasizing their ability to deal with obesity via pancreatic lipase inhibition. MethodsThe study followed two stages, i.e. systematic review and meta-analysis. Data from 6 scientific (Scopus, Science Direct, Proquest, Ebsco, Cengage Library and Emerald) were collected, screened according to inclusion and exclusion criteria. The eligibility of the trials was determined according to criteria as follows: (1) design for lipase inhibition experiments; (2) population in all researches using in vitro protocols for antiobesity in last 10 years; (3) intervention for comparison between lipase inhibition IC50 properties of selected medicinal plants and orlistat; and (4) data adequacy enabling to estimate the standardized mean difference (SMD) and the corresponding 95% confidence interval (CI). Further, all published papers we reviewed were written in English. Furthermore, steps of meta-analysis were performed on the selected data. Extraction of data in these articles collected number of samples, average values and standard deviation of IC50. The values focused on IC50 of samples in inhibiting lipase activities performed by plant extracts and orlistat as control. ResultA total 10 selected data meet the inclusion criteria. Morever these plant can be found and common as traditional medicine plant in Indonesia ConclusionAs the results, there were top 10 anti-obesity medicinal plants as follows: i.e. kelor (Moringa oleifera) leaves, kemangi (Ocimum basilicum) leaves, asam jawa (Tamarindus indica) leaves, asam gelugur (Garcinia atroviridis) fruit, lengkuas (Alpinia galanga) rhizome, and kencur (Kaempferia galanga) rhizome, kumis kucing (Orthosipon aristatus) leaves, jambu biji leaves (Psidium guajava leavaes), serai wangi (Cymbopogon nardus) and kayu secang (Caesalpinia sappan).
Transcriptome Analysis of gene in Mouse M-1 cells revealing the functional mechanism of Astragali radix extract
Authors: Wang Bing , Feng Qian , zhang chao , Chen Yuming , Chen Yu , Teng Jie , Cai Zhongzhen , Li Mengmei , Wang Lin , Zhao Yanpeng , Bai Xuemei 
Published: September 2021

Abstract
Background
Astragali Radix (AR),the dried root of legumes, belongs to the Qi- invigorating herbs in traditional Chinese medicine and plays an important role in the treatment of many diseases. In order to understand the mechanism of action of AR extract, we used AR extract to treat M-1, mouse kidney cells, and used transcriptome sequencing technology to detect the genomic transcription level of the cells under the action of AR at different concentrations and times.
Result
The results showed that after a low concentration of AR treatments on the cells, the expression of genes related to cell growth and cellular immune response changed significantly, among which multiple genes are related to mitochondrial function, while high concentrations of AR affected the expression of histones and disease-related genes. It showed that the low concentration of AR extract can achieve the effect of invigorating Qi by regulating the function of mitochondria. In addition, several important genes and pathways were identified as potential targets of AR activation.
Conclusion
The research not only clarified the main molecular biological mechanism of AR invigorating Qi, but also provided experimental basis and cellular physiology reference for the further clinical application of AR.
Network pharmacology, molecular docking, and experimental study for the mechanisms of Qishen Yiqi Pills against Cardiovascular Diseases
Authors: Zhao Jie-wen , Liu Hai-dong , Man Ming-yin , Wang Lv-ya , Li Ning , Zhao Jing , Cheng Wen-li , Yu Kai-jiang 
Published: September 2021

Abstract
Background

Qishen Yiqi Pills (QSYQP) is a traditional Chinese compound recipe. However, our understanding of its mechanism has been hindered due to the complexity of its components and targets. In this work, the network pharmacology-based approaches were used to explore QSYQP’s pharmacological mechanism on treating cardiovascular diseases (CVD).
Results

From ETCM and TCM MESH databases we collected QSYQP’s 333 active components and their 674 putative targets. We constructed the sub-network influence by CVD genes and found that 40% QSYQP targets appeared in 20 modules, in which QSYQP’s targets and CVD genes co-existed as hub nodes in the sub-network. Functional enrichment analysis suggested that the 42 key targets were mainly expressed in platelets, blood vessels, cardiomyocytes, and other tissues. The main signaling pathways regulated and controlled by the key targets were inflammation, immunity, blood coagulation and energy metabolism. Network and pathway analysis identified 7 key targets, which were regulated by 7 compounds of QSYQP. 26 of the 42 important targets, including the 7 key targets were verified by literature mining. Twelve pairs of interactions between key targets and QSYQP’s compounds were validated by molecular docking. Further validation experiments suggested that QSYQP suppressed H/R induced apoptosis and cytoskeleton disruption of cardiomyocytes. Western blotting showed that the expression of cardiovascular diseases-related genes including ACTC1, FoxO1 and DIAPH1 was significantly decreased by establishing the hypoxia-reoxygenation model in vitro, while the protein expression of experimental group was significantly increased by adding QSYQP or its ingredients.
Conclusion

These results indicated the correlation of QSYQP treatment to the therapeutic effects of CVD. At the molecular level, this study revealed the multicomponent and multitargeting mechanisms of QSYQP in the regulation and treatment of cardiovascular diseases, potentially providing a reference for the further utilization of QSYQP.
How do we engage people in testing for COVID-19? A rapid qualitative evaluation of a testing programme in schools, GP surgeries and a university
Authors: Watson Daniella , Baralle Natalia Laverty , Alagil Jawahr , Anil Krithika , Ciccognani Sandy , Dewar-Haggart Rachel , Fearn Sarah , Groot Julia , Knowles Kathryn , Meagher Claire , McGrath Carmel , Muir Sarah , Musgrove Jo , Glyn-Owen Kate , Woods-Townsend Kath , Mortimore Andrew , Roderick Paul , Baird Janis , Inskip Hazel , Godfrey Keith , Barker Mary 
Published: September 2021

Abstract
Background
The UK Scientific Advisory Group for Emergencies (SAGE) emphasises the need for high levels of engagement with communities and individuals to ensure the effectiveness of any COVID-19 testing programme. A novel pilot health surveillance programme to assess the feasibility of weekly community RT-LAMP testing for the SARS-CoV-2 virus using saliva samples collected at home was developed and piloted by the University of Southampton and Southampton City Council.
Methods
Rapid qualitative evaluation was conducted to explore experiences of those who took part in the programme, of those who declined and of those in the educational and healthcare organisations involved in the pilot testing who were responsible for roll-out. This included 77 interviews and 20 focus groups with 223 staff, students, pupils and household members from four schools, one university, and one community healthcare NHS trust. The insights generated informed the design and modification of the Southampton COVID-19 Saliva Testing Programme and the next phase of community-testing.
Results
Conversations revealed that high levels of communication, trust and convenience were necessary to ensure people’s engagement with the programme. This suggests community leaders and stakeholder organisations should be involved throughout programme development and implementation to optimise these features of the testing.
Conclusions
Participants’ and stakeholders’ motivations, challenges and concerns need to be understood and these insights used to modify the programme in a continuous, real-time process to ensure and sustain engagement with testing over the extended period necessary.