bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel Combination of Bevacizumab and Pembrolizumab Stimulates Tumour Immunity Through Vascular Normalisation in Humanised Mouse Model
Authors: Qiao Tianyun , Guo Wenwen , Meng Fancheng , Zhou Yongsheng , Xiong Yanlu , Feng Yangbo , Zhang Caiqin , Wu Yingtong , Zhao Jinbo , Jiang Tao , Shi Changhong , Han Yong 
Published: January 2021

Abstract
Background: Immunotherapy has dramatically changed the treatment landscape of cancer. Immunotherapies targeting the programmed death 1/programmed death ligand 1 pathway have been shown to lead to durable responses in patients with a variety of cancers. However, combination approaches are required to extend this benefit beyond a subset of patients. Studies have suggested that anti-angiogenic therapy can elicit or enhance tumor immunity response.Therefore, we hypothesised that combining immunotherapy with anti-angiogenic treatment may have a synergistic effect and may enhance the efficacy of both treatments.Methods: We evaluated the combination of bevacizumab (anti-vascular endothelial growth factor monoclonal antibody) and pembrolizumab (anti-programmed death 1 monoclonal antibody) in two mouse models of human non-small cell lung cancer cell lines (H1299 and A549). We monitored tumour growth and examined changes in the tumour vasculature, along with the frequency and phenotype of tumour-infiltrating lymphocytes.Results: The combination of bevacizumab and pembrolizumab synergistically inhibited tumour growth in vivo without overt toxicity in both cell lines. Combination therapy reprogrammed the immune microenvironment by increasing CD8+ cytotoxic T cell infiltration, thereby turning tumours with different phenotypes into inflamed (‘hot’) tumours. This is potentially mediated by vascular normalisation and endothelial cell activation, as demonstrated by a reduction in the number of microvessels and an increase in adhesion molecules.Conclusions: Taken together, our preclinical studies demonstrate that the combination of bevacizumab and pembrolizumab had a synergistic anti-tumour effect and provides a theoretical basis for translating basic research into clinical applications.
Multicriteria Recommender System: A New Model for Determining risk level of COVID-19 in Indonesia
Authors: Hikmawati Erna , Maulidevi Nur Ulfa , Surendro Kridanto 
Published: January 2021

Abstract
Coronavirus has spread all over the world and brought significant impact to everyday life. This highly infectious virus calls for new strategies and policies that are able to suppress its transmission rate. One of the ways is by lockdown. However, lockdown is not an infallible solution and it brings with it negative impacts on society in terms of socioeconomic and mental health aspects. In addition, several factors should also be taken into account before the implementation such as demographic conditions, health services and COVID-19 case data itself. In general, a lockdown decision can be determined by looking at the level of risk of an area. Naturally, this assessment of levels of risk must be based on parameters affecting the lockdown. In this paper, we propose a multicriteria recommender system model that can calculate the value and level of risk for each region by taking into account several parameters from different databases. This model is also equipped with the process of weighting using the Analytical Network Process (ANP) method to determine interdependence and feedback between parameters. From the experiment conducted on 27 cities and districts in West Java, it was found that 15% of the regions were in the high-risk category, 41% of the regions have medium risk and 44% of the regions have a low risk.
Quantifiable Breathing Pattern Components Can Predict Asthma Control: an Observational Cross-sectional Study
Authors: Sakkatos Panagiotis , Bruton Anne , Barney Anna 
Published: January 2021

Abstract
Background: Breathing pattern disorders are frequently reported in uncontrolled asthma. At present, this is primarily assessed by questionnaires, which are subjective. Objective measures of breathing pattern components can provide additional useful information about asthma control. This study examined whether respiratory timing parameters and thoracoabdominal (TA) motion measures could predict and classify levels of asthma control. Methods: 122 asthma patients at STEP 2- STEP 5 GINA asthma medication were enrolled. Asthma control was determined by the Asthma Control Questionnaire (ACQ7-item) and patients divided into ‘well controlled’ or ‘uncontrolled’ groups. Breathing pattern components (respiratory rate (RR), ratio of inspiration duration to expiration duration (Ti/Te), ratio of ribcage amplitude over abdominal amplitude during expiration phase (RCampe/ABampe), were measured using Structured Light Plethysmography (SLP) in a sitting position for 5-minutes. Breath-by-breath analysis was performed to extract mean values and within-subject variability (measured by the Coefficient of Variance (CoV%). Binary multiple logistic regression was used to test whether breathing pattern components are predictive of asthma control. A post-hoc analysis determined the discriminant accuracy of any statistically significant predictive model. Results: Fifty-nine out of 122 asthma patients had an ACQ7-item < 0.75 (well-controlled asthma) with the rest being uncontrolled (n= 63). The absolute mean values of breathing pattern components did not predict asthma control (R2 = 0.09) with only mean RR being a significant predictor (p < 0.01). The CoV% of the examined breathing components did predict asthma control (R2 = 0.45) with all predictors having significant odds ratios (p < 0.01). The ROC curve showed that cut-off points > 7.40% for the COV% of the RR, > 21.66% for the CoV% of Ti/Te and > 18.78% for the CoV% of RCampe/ABampe indicated uncontrolled asthma. Conclusion: The within-subject variability of timing parameters and TA motion can be used to predict asthma control. Higher breathing pattern variability was associated with uncontrolled asthma suggesting that irregular resting breathing is an indicator of poor asthma control.
The Infectivity and Antigenicity of Epidemic SARS-CoV-2 Variants in the United Kingdom
Authors: Wang Youchun , Wu Jiajing , Zhang Li , Zhang Yue , Wang Haixin , Ding Ruxia , Nie Jianhui , Li Qianqian , Liu Shuo , Yu Yongxin , Yang Xiao-Ming , Qu Xiaowang , Duan Kai , Huang Weijing 
Published: January 2021

Abstract
The SARS-CoV-2 variant VUI/202012/01 has been reported to spread unexpectedly fast in the United Kingdom. It is estimated that its transmissibility may increase by 70%. In this study, the top five variants circulating in the UK including D614G+L18F+A222V, D614G+A222V, D614G+S477N, VUI/202012/01 and D614G+69-70del+439K were analyzed for their infective and neutralizing characteristics. The pseudotyped viruses were constructed for the five variants and 12 single mutants composed those variants. We found that the VUI/202012/01 variant does enhance its infectivity due to the cumulative effect of multiple mutations including 69-70del and 144/145del mutations in NTD, A570D in RBD, and S982A in S2. Meanwhile, mutations N501Y, N439K and S477N in RBD can cause a significant decrease in the neutralization activity for some mAbs. Although VUI/202012/01 did not affect the neutralization effect of convalescent sera, it affected the neutralization activity of animal immunized sera by RBD protein or recombinant spike DNA to some extent.
Double-blinded placebo-controlled trial measuring cartilage improvement in early Rheumatoid Arthritis under Adalimumab therapy using MRI
Authors: Frenken Miriam , Sewerin Philipp , Brinks Ralph , Vordenbäumen Stefan , Schleich Christoph , Müller-Lutz Anja , Antoch Gerald , Richter Jutta , Sander Oliver , Schneider Matthias , Abrar Daniel B. , Ostendorf Benedikt 
Published: January 2021

Abstract
Background: To compare the effect of Adalimumab (ADA) plus Methotrexate (MTX) versus MTX monotherapy in patients with therapy naïve early rheumatoid arthritis (eRA) on cartilage quality measured by glycosaminoglycan (GAG) content in cartilage using gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC). Methods: Prospective double-blinded, randomized clinical trial of cartilage integrity in finger joints of eRA patients according to American College of Rheumatology/ European League Against Rheumatism. Patients were examined therapy-naïve, 12 and 24 weeks after initiation of Adalimumab+MTX or placebo+MTX with 3T-MRI, recording dGEMRIC values of metacarpophalangeal joints of index and middle finger. Results: The study was prematurely terminated due to theoretical safety concerns regarding gadolinium deposition in the brain after MR contrast agent application. Instead of 30 planned patients, 10 patients could be included in the Adalimumab group (ADA+MTX: 6 females, 44.9y, range: 19-65), four in the control group (Placebo+MTX: 2 females, 46.7y, range: 24-64). Between treatment groups, cartilage composition did not change significantly (ADA+MTX: dGEMRIC mean change 85.8ms, range -156.2–346.5ms; Placebo+MTX: mean change-30.75ms, range-273.0–131.0ms; W=27, p=0.37). Neverthless a significant increase of the dGEMRIC values over time was observed in the Adalimumab group (median change 75.88 ms p=0.0117), but not in the placebo group (median change 9.50, p=0.878).Conclusions: In patients with eRA, Adalimumab+MTX leads to a significant dGEMRIC improvement, indicating a possible reduction of cartilage damage in the finger joints. The level of significance for the difference of change in cartilage quality between groups, was not met, potentially due to lower than expected number of patients which could be recruited. Trial registration: The cartilage in early Rheumatoid Arthritis (CAR-ERA)-Study was approved by the local ethics committee of the Heinrich-Heine University of Duesseldorf (reference number: MO-LKP-719) and was registered at clinicaltrials.gov under the number NCT02150473 / CAR-ERA 2013-004604-19 (EudraCT Number).
Induced neural stem cell grafts exert neuroprotection through an interaction between Crry and Akt in a mouse model of closed head injury
Authors: Gao Mou , Dong Qin , Wang Wenjia , Yang Zhijun , Guo Lili , Lu Yingzhou , Ding Boyun , Chen Lihua , Zhang Jianning , Xu Ruxiang 
Published: January 2021

Abstract
Background: Recently, growing evidence has indicated an important role of the complement system, a crucial component of immunity, in mediating neuroinflammation and promoting neuronal apoptosis following closed head injury (CHI). We previously reported that transplanted induced neural stem cells (iNSCs) pre-treated with CHI mouse serum could enhance complement receptor type 1-related protein y (Crry) expression and ameliorate complement-mediated damage in mouse CHI models. However, the mechanism underlying the elevated levels of Crry expression remains elusive. Methods: CHI models were established using a standardized weight-drop device. We collected CHI mouse serum at 12 h post-trauma. RT-QPCR assay, western blot analysis, complement deposition assay, Akt inhibition assay, flow cytometry, cell transplantation and functional assay were utilized to clarify the mechanism of Crry expression in iNSCs receiving CHI mouse serum treatment.Results: We observed dramatic increases in the levels of Crry expression and Akt activation in iNSCs receiving CHI mouse serum treatment. Remarkably, Akt inhibition led to the reduction of Crry expression in iNSCs. Intriguingly, the treatment of iNSC-derived neurons with recombinant complement receptor 2-conjugated Crry (CR2-Crry), which inhibits all complement pathways, substantially enhanced Crry expression and Akt activation in neurons after CHI mouse serum treatment. In subsequent in vitro experiments of pre-treatment of iNSCs with CR2-Crry, we observed significant increases in the levels of Crry expression and Akt activation in iNSCs, iNSC-derived astrocytes and neurons post-treatment with CHI mouse serum. Additionally, an in vivo study showed that intracerebral-transplanted iNSCs pre-treated with CR2-Crry markedly enhanced Crry expression in neurons and protected neurons from complement-dependent damage in the brains of CHI mice. Conclusion: INSCs receiving CR2-Crry pre-treatment increased the levels of Crry expression in iNSCs, iNSC-derived astrocytes and neurons and attenuated complement-mediated injury following CHI.
Effect of a nurse-led lifestyle choice and coaching intervention on systolic blood pressure among Type 2 diabetic patients with a high atherosclerotic cardiovascular risk: study protocol for a cluster randomized trial
Authors: Lumu William , Kibirige Davis , Wesonga Ronald , Bahendeka Silver 
Published: January 2021

Abstract
Background:More than 50% of patients with type 2 diabetes have hypertension in Uganda. Diabetic patients with elevated systolic blood pressure experience higher all-cause mortality and cardiovascular events compared with normotensive diabetic individuals hence escalating resource utilization and cost of care. The aim of this study is to determine the effect of a nurse-led lifestyle choice and coaching intervention on systolic blood pressure among type 2 diabetic patients with a high atherosclerotic cardiovascular risk.Methods:This is a cluster-randomized study comprising of two arms (intervention and non-intervention – control arm) with four clusters per arm with 388 diabetic patients with a high predicted 10-year atherosclerotic cardiovascular risk. The study will be implemented in 8 health facilities in Uganda. The intervention arm will employ a nurse-led lifestyle choice and coaching intervention. Within the intervention, nurses will be trained to provide structured health education, protocol-based hypertension management and general atherosclerotic cardiovascular risk factor management, 24-hour phone calls, and 2-monthly text messaging. The control group will be constituted by the usual care. The primary outcome measure is the mean difference in systolic blood pressure between the intervention and usual care groups after 6 months. The study is designed to have an 80% statistical power to detect an 8.5mmhg mean reduction in systolic blood pressure from baseline to 6 months. The unit of analysis for the primary outcome is the individual participants. To monitor the effect of within-cluster correlation, generalized estimating equations will be used to assess changes over time in systolic blood pressure as a continuous variable.DiscussionThe data generated from this trial will inform change in policy of shifting task of screening of hypertension and atherosclerotic cardiovascular disease from doctors to nurses
A Cross-sectional, Multicenter, Observational Study to Assess the Prophylaxis of Venous Thromboembolism in Lebanese and Jordanian Hospitals
Authors: Hajj Imad , -Masri Mahmoud AL , Bashaireh Kaldoun , Hani Mohammed Bani , Hamouri Shadi , Khouzami Joe , Sabra Nisrine , Fadel Chahine 
Published: January 2021

Abstract
BackgroundThere is a growing body of evidence showing substantial underuse of appropriate venous thromboembolism (VTE) prophylaxis in patients at risk. In the present study, our goal was to assess the current practices in the use rate of VTE prophylaxis among hospitalized patients in Jordan and Lebanon.MethodsA cross-sectional, multicenter, observational study was conducted on 40 centers across Lebanon and Jordan. We included patients who were admitted to the participating hospitals for the treatment of a serious medical or surgical illness. The patients’ records were screened for the fulfillment of inclusion/exclusion criteria during a single assessment visit. The proportion of medical and surgical patients who were at risk of VTE and the thrombo-prophylactic measures employed by physicians for these patients were assessed according to the American College of Chest Physicians (ACCP 2016) guidelines. ResultsThe present study included 704 patients (400 from Jordan and 304 from Lebanon) with a mean age of 54.9 ±17.5 years. Almost 59% of the patients received prophylaxis treatment in form of pharmacological anticoagulant prophylaxis and/or mechanical prophylaxis. Low molecular weight heparin was the most commonly used anticoagulant for VTE prophylaxis in 366 out of the total 704 (51.9%) patients in the analysis cohort. Two hundred and sixteen patients (52 %, 95% confidence interval [47.1% - 56.9%]) received appropriate prophylactic agents out of 415 patients who were eligible for prophylaxis according to the ACCP 2016 guidelines. On the other hand, 199 (72.1%, 95% confidence interval [66.4% – 77.3%) patients received prophylaxis out of 276 ineligible patients. The rate of compliance to guidelines showed wide variations according to the type of hospital, specialty, and the patients’ age. The multivariate logistic regression analysis showed that only age was a significant predictor of appropriate VTE prophylaxis (odds ratio [OR] 1.05, P <0.001).ConclusionThe rates of the appropriate use of VTE prophylaxis are low in Lebanon and Jordan. There is a lack of compliance to guidelines for VTE prophylaxis use for hospitalized patients in both countries.
The circular RNA circZFR phosphorylates Rb promoting cervical cancer progression by regulating the SSBP1/CDK2/cyclin E1 complex
Authors: Zhou Mingyi , Yang Zhuo , Wang Danbo , Chen Peng , Zhang Yong 
Published: January 2021

Abstract
Background: As a novel type of non-coding RNA, circular RNAs (circRNAs) play a critical role in the initiation and development of various diseases, including cancer. However, the exact function of circRNAs in human cervical cancer remains largely unknown. Methods: We identified the circRNA signature of upregulated circRNAs between cervical cancer and paired adjacent normal tissues. Using two different cohorts and GEO database, a total of six upregulated circRNAs were identified with a fold change >2, and P <0.05. Among these six circRNAs, hsa_circ_0072088 (circZFR) was the only exonic circRNA significantly overexpressed in cervical cancer. Functional experiments were performed to investigate the biological function of circZFR. CircRNA pull-down, circRNA immunoprecipitation (circRIP) and Co-immunoprecipitation (Co-IP) assays were executed to investigate the molecular mechanism underlying the function of circZFR.Results: Functionally, circZFR knockdown represses the proliferation, invasion, and tumor growth. Furthermore, circRNA pull-down experiments combined with mass spectrometry unveil the interactions of circZFR with Single-Stranded DNA Binding Protein 1 (SSBP1). Mechanistically, circZFR bound with SSBP1, thereby promoting the assembly of CDK2/cyclin E1 complexes. The activation of CDK2/cyclin E1 complexes induced p-Rb phosphorylation, thus releasing activated E2F1 leading to cell cycle progression and cell proliferation. Conclusion: Our findings provide the first evidence that circZFR is a novel onco-circRNA and might be a potential biomarker and therapeutic target for cervical cancer patients.
Identification of Key Genes in Hepatitis B Associated Hepatocellular Carcinoma Based on WGCNA
Authors: Liu Chang , Dai Qinghai , Ding Qian , Wei Min , Kong Xiaohong 
Published: January 2021

Abstract
Hepatitis B virus (HBV) chronic infection is one risk factor of hepatocellular carcinoma (HCC). Lots of efforts have been made to illuminate the process of HBV-associated HCC, but its molecular mechanisms of carcinogenesis remain vague. Here, weighted gene co-expression network analysis (WGCNA) was employed to explore the co-expressed modules and hub/key genes correlated to HBV-associated HCC. We found that genes of the most significant module related to HBV-associated HCC were enriched in DNA replication, p53 signaling pathway, cell cycle, and HTLV-1 infection associated pathway; these cellular pathways played critical roles in the initiation and development of HCC or viral infections. Furthermore, seven hub/key genes were identified based on the topological network analysis, and their roles in HCC were verified by expression and Kaplan-Meier survival analysis. Protein-protein interaction and KEGG pathway analysis suggested that these key genes may stimulate cellular proliferation to promote the HCC progression. This study provides new perspectives to the knowledge of the key pathways and genes in the carcinogenesis process of HBV-associated HCC, and our findings provided potential therapeutic targets and clues of the carcinogenesis of HBV-associated HCC.
Improved performances of lithium disilicate glass-ceramics by seeds induced crystallization
Authors: Zhao Ting , Lian Mei-Mei , Qin Yi , Zhu Jian-Feng , Kong Xin-Gang , Yang Jian-Feng 
Published: January 2021

Abstract
Self-reinforced lithium disilicate (Li 2 Si 2 O 5 ) glass-ceramics were hot pressing sintered by introducing 5 wt% Li 2 Si 2 O 5 crystal seeds into two different glass systems. The results show that the seeds play an important role in the crystallization inducement, microstructural and properties improvement of the glass, especially for the glass powder without the nucleating agent of P 2 O 5 . The microstructure features a wider bimodal grain size distribution with large rod-like crystals epitaxially grown along the seeds and small crystals nucleated from the glass powder itself, contributes to the improvement of the performance especially the fracture toughness. The 4C5S specimen exhibited the best comprehensive properties with a good flexural strength (396 ± 7 MPa), improved fracture toughness (3.31 ± 0.19 MPa·m 1/2 ) and comparable translucency as IPS e.max. This research will provide a new idea and method for the perfect matching of the fracture toughness and the aesthetic appearance of lithium disilicate glass-ceramics, and lay the foundation for its clinical applications.
The impact of financial incentives on SNAP transactions at mobile produce markets
Authors: Rummo Pasquale , Lyerly Reece , Rose Jennifer , Malyuta Yelena , Cohen Eliza Dexter , Nunn Amy 
Published: January 2021

Abstract
Background. Offering financial incentives promotes increases in fruit and vegetable purchases in farmers’ markets and supermarkets. Yet, little is understood about whether food-insecure adults purchase more fruits and vegetables as a result of receiving financial incentives in mobile produce market settings.Methods. In 2018-2019, Food on the Move provided a 50% discount to customers using Supplemental Nutrition Assistance Program (SNAP) benefits to purchase fruit and vegetables from 16 market locations in Rhode Island (n=412 market occasions). We used mixed multivariable linear regression to estimate the difference in total dollar sales per transaction per month between SNAP transactions and non-SNAP transactions. We also estimated the difference in out-of-pocket dollar sales per transaction per month between SNAP and non-SNAP transactions, less the 50% discount. This reflects the actual amount spent on fresh fruits and vegetables purchased per visit. In both models, we controlled for the number of market sites per month, with fixed effects for quarter and year. We estimated random intercept variance for date of transaction and market site to adjust for clustering.Results. In 2018-2019, the majority of market transactions (total n=13,165) were SNAP transactions [n=7.988 (63.0%)]. On average, customers spent $17.38 (SD=16.69) on fruits and vegetables per transaction per month. However, customers using SNAP benefits spent significantly more on FVs per transaction per month [$22.01 (SD=17.97)] compared to those who did not use SNAP benefits [9.81 (SD=10.68)] (β=$10.88; 95% CI: 10.18, 11.58). Similarly, out-of-pocket dollar sales per SNAP transaction per month (i.e., less the 50% discount) were significantly higher [$11.42 (SD=9.44)] relative to non-SNAP transactions [$9.40 (SD=9.33)] (β=$1.85; 95% CI: 1.44, 2.27).Conclusions. Financial incentives contributed to higher fruit and vegetable purchases among low-income customers who shop at mobile produce markets compared to non-eligible customers. Higher spending on fruits and vegetables may promote healthy diet behaviors and reduce chronic disease risk among food-insecure adults.