bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apatinib suppresses tumor progression and enhances cisplatin sensitivity in esophageal cancer via the Akt/β-catenin pathway
Authors: Wei Bin , Wang Yuanyuan , Wang Jiawei , Cai Xiaomin , Xu Lingyan , Wu Jingjing , Wang Ying , Liu Wen , Gu Yanhong , Guo Wenjie , Xu Qiang 
Published: May 2020

Abstract
Background
Esophageal cancer is the sixth leading cause of cancer-related mortality worldwide, which is partially due to limited progress of therapy. Apatinib, an inhibitor of VEGFR2, has a promising antitumor effect on malignancies. However, the underlying mechanism of its antitumor effect on esophageal cancer remains poorly understood.

Materials and methods
Eighteen pairs of frozen esophageal cancer and their para-cancer samples and 25 paraffin specimens from advanced esophageal cancer patients treated with cisplatin-based regimen were collected. The effects of apatinib on cell growth, cell apoptosis, cell cycle and invasion/migration of esophageal cancer cells were assessed. Bioinformatics, luciferase reporter, immunoprecipitation and immunofluorescence assays were conducted for mechanic investigation. Quantitative RT-PCR, western blotting and immunohistochemistry were used to measure the expression of functional genes. Xenograft tumor growth of mice was performed.

Results
We found that VEGFR2 was highly expressed in esophageal cancer and associated with poor efficacy of cisplatin-based treatment. Apatinib displayed profound actions against tumor cell growth of human esophageal cancer via promoting cell apoptosis and cell cycle arrest. Also, apatinib displayed the inhibitory effects on cell migration and invasion. Moreover, apatinib strongly suppressed the growth of esophageal cancer xenografts in mice. The effects of apatinib on esophageal cancer were partially dependent on its block of the VEGFR2/Akt/β-catenin pathway. Specifically, apatinib induced the degradation of β-catenin and decreased its transcriptional activity through Akt/GSK-3β repression. Further in vitro and in vivo studies revealed that low dose apatinib had a synergistic antitumor effect with cisplatin on esophageal cancer.

Conclusion
Our study indicates that apatinib suppresses tumor progression and enhances cisplatin sensitivity in esophageal cancer by deactivating the Akt/β-catenin pathway. These findings provide a theoretical foundation for using apatinib as an effective therapeutic drug for esophageal cancer.
Leaving no one behind – understanding environmental inequality in Europe
Authors: Ganzleben Catherine , Kazmierczak Aleksandra 
Published: May 2020

AbstractThe European Union aims to deliver a healthy environment to its citizens, with significant progress achieved in tackling key environmental stressors in recent decades. At the same time, significant risks to health remain from air, soil and water pollution, noise, chemicals and the impacts of climate change. High quality environments - such as urban areas rich in green and blue spaces - offer significant benefits to health. The unequal distribution of these risks and benefits across society, whereby socially disadvantages groups are more likely to live in poorer environmental conditions, contributes to health inequity across Europe.The European Environment Agency (EEA) is exploring how environmental risks and benefits are distributed across society. Recent evidence produced by EEA indicated that poorer European regions are more likely to be exposed to environmental health hazards at levels that negatively affect health. At country level, the disproportionate exposure of lower socio-economic groups to air pollution, noise and high temperatures is seen in urban areas. We also see inequality in terms of who generates pollution and who suffers the consequences. While poorer countries are likely to be worse affected by climate change, high incomes are linked to high carbon footprints across Europe. Quality environments offer benefits to health, in particular in urban areas, and can contribute to reducing health inequalities. Environmental inequality also plays out across generations, whereby future generations will have to tackle environmental degradation resulting from the activities of past and current populations, such as the accumulation of persistent chemicals in the environment, biodiversity loss and climate change.New opportunities exist to explore the complex linkages between environmental quality, socio-economic status, and health and well-being. These include combining existing data from across these domains with data from new sources, such as citizen science initiatives, smart phones, social media and satellite observation data. Knowledge that integrates the social and environmental domains and explores the drivers behind environmental health inequity is crucial to supporting implementation of the United Nations (UN) 2030 Agenda for Sustainable Development, in particular the pledge of leaving no one behind.
Role of non-statin lipid-lowering therapy in coronary atherosclerosis regression: a meta-analysis and meta-regression
Authors: Masson Walter , Lobo Martin , Siniawski Daniel , Molinero Graciela , Masson Gerardo , Huerín Melina , Nogueira Juan Patricio 
Published: May 2020

Abstract
Background
Several studies have investigated the association between non-statin lipid-lowering therapy and regression of atherosclerosis. However, these studies were mostly small and their results were not always robust. The objectives were: (1) to define if a dual lipid-lowering therapy (statin + non-statin drugs) is associated with coronary atherosclerosis regression, estimated by intravascular ultrasound (IVUS); (2) to assess the association between dual lipid-lowering-induced changes in low density lipoprotein cholesterol (LDL-C) and non-high-density-lipoprotein cholesterol (non-HDL-C) levels and atherosclerosis regression.

Methods
A meta-analysis including trials of non-statin lipid-lowering therapy, reporting LDL-C, non-HDL-C and total atheroma volume (TAV) with a minimum of 6 months of follow-up was performed. The primary endpoint was defined as the change in TAV measured from baseline to follow-up, comparing groups of subjects on statins alone versus combination of statin and non-statin drugs. The random-effects model and meta-regression were performed.

Results
Eight eligible trials of non-statin lipid-lowering drugs (1759 patients) were included. Overall, the dual lipid-lowering therapy was associated with a significant reduction in TAV [− 4.0 mm3 (CI 95% -5.4 to − 2.6)]; I2 = 0%]. The findings were similar in the stratified analysis according to the lipid-lowering drug class (ezetimibe or PCSK9 inhibitors). In the meta-regression, a 10% decrease in LDL-C or non-HDL-C levels, was associated, respectively, with 1.0 mm3 and 1.1 mm3 regressions in TAV.

Conclusion
These data suggests the addition of ezetimibe or PCSK9 inhibitors to statin therapy results in a significant regression of TAV.
Reduction of coronary atherosclerosis observed with non-statin lipid-lowering therapy is associated to the degree of LDL-C and non-HDL-C lowering. Therefore, it seems reasonable to achieve lipid goals according to cardiovascular risk and regardless of the lipid-lowering strategy used (statin monotherapy or dual treatment).
Association between fatigue, pain, digestive problems, and sleep disturbances and individuals’ health-related quality of life: a nationwide survey in South Korea
Authors: Baek Younghwa , Jung Kyungsik , Kim Hoseok , Lee Siwoo 
Published: May 2020

Abstract
Background
Physical symptoms such as fatigue, pain, digestive problems, and sleep disturbances are chief reasons individuals seek primary care, as they affect health-related quality of life. We investigated the associations between various combinations of these common symptoms and individuals’ health-related quality of life.

Methods
This large-scale survey study of 1100 Koreans aged ≥19 years was conducted in 2017 using multi-stage stratified sampling based on region, sex, and age. Data were collected using questionnaires administered face-to-face; then, a linear regression analysis was performed to assess how the symptoms were related to participants’ health-related quality of life. Complex symptoms were defined as co-occurrence of two or more of the four symptoms—fatigue, pain, digestive problems, and sleep disturbances.

Results
The most frequently observed stand-alone symptom was fatigue, while the most common combination was fatigue and pain. When examined individually, fatigue, digestive problems, and sleep disturbances were closely associated with mental health-related quality of life, and pain was associated with physical health-related quality of life. Complex symptoms were also related to health-related quality of life. Lower physical health-related quality of life was strongly associated when fatigue and pain or all four symptoms were co-occurring, and the lowest mental health-related quality of life was seen when all four symptoms were present, after adjusting for all variables.

Conclusions
Symptoms can be present in various combinations and are significantly associated with health-related quality of life. Extra attention should be given to patterns accompanying fatigue and pain and to those involving more symptoms. This elucidated the characteristics of symptoms that affect the health-related quality of life of South Korean adults.
Protocol for a matched-pair cluster control trial of ARCHES (Addressing Reproductive Coercion in Health Settings) among women and girls seeking contraceptive services from community-based clinics in Nairobi, Kenya
Authors: Uysal Jasmine , Carter Nicole , Johns Nicole , Boyce Sabrina , Liambila Wilson , Undie Chi-Chi , Muketo Esther , Adhiambo Jill , Gray Kate , Wendoh Seri , Silverman Jay G. 
Published: May 2020

AbstractBackgroundReproductive coercion (RC) and intimate partner violence (IPV) are prevalent forms of gender-based violence (GBV) associated with reduced female control over contraceptive use and subsequent unintended pregnancy. Although the World Health Organization has recommended the identification and support of GBV survivors within health services, few clinic-based models have been shown to reduce IPV or RC, particularly in low or middle-income countries (LMICs). To date, clinic-based GBV interventions have not been shown to reduce RC or unintended pregnancy in LMIC settings.InterventionARCHES (Addressing Reproductive Coercion in Health Settings) is a single-session, clinic-based model delivered within routine contraceptive counseling that has been demonstrated to reduce RC in the United States. ARCHES was adapted to the Kenyan context via a participatory process to reduce GBV and unintended pregnancy among women and girls seeking contraceptive services in this setting. Core elements of ARCHES include enhanced contraceptive counseling that addresses RC, opportunity for patient disclosure of RC and IPV (and subsequent warm referral to local services), and provision of a palm-sized educational booklet.MethodsA matched-pair cluster control trial is being conducted to assess whether the ARCHES intervention (treatment condition), as compared to standard-of-care contraceptive counseling (control condition), reduces RC and IPV, and improves contraceptive outcomes for woman and girls of reproductive age (15 to 49 years) seeking contraceptive services from community-based clinics in Nairobi, Kenya. All six clinics were assigned to intervention-control pairs based on similarities in patient volume and demographics, physical structure and neighborhood context. Survey data will be collected from patients immediately prior to their clinic visit (baseline, T1), immediately after their clinic visit (exit), and at 3- and 6-months post-visit (T2 and T3, respectively).DiscussionThis study is the first to assess the efficacy of an adaptation of the ARCHES model to reduce GBV and improve reproductive health outside of the U.S., and one of only a small number of controlled trials to assess reductions in GBV associated with a clinic-based program in an LMIC context. Evidence from this trial will inform health system efforts to reduce GBV, and to enhance female contraceptive control and reproductive health in Kenya and globally.Trial registrationRegistered May 23, 2018 -ClinicalTrials.gov,NCT03534401. Unique Protocol ID: 170084.
Examining the accuracy of trackways for predicting gait selection and speed of locomotion
Authors: Marmol-Guijarro Andres , Nudds Robert , Folkow Lars , Codd Jonathan 
Published: May 2020

Abstract
Background
Using Froude numbers (Fr) and relative stride length (stride length: hip height), trackways have been widely used to determine the speed and gait of an animal. This approach, however, is limited by the ability to estimate hip height accurately and by the lack of information related to the substrate properties when the tracks were made, in particular for extinct fauna. By studying the Svalbard ptarmigan moving on snow, we assessed the accuracy of trackway predictions from a species-specific model and two additional Fr based models by ground truthing data extracted from videos as the tracks were being made.

Results
The species-specific model accounted for more than 60% of the variability in speed for walking and aerial running, but only accounted for 19% when grounded running, likely due to its stabilizing role while moving faster over a changing substrate. The error in speed estimated was 0–35% for all gaits when using the species-specific model, whereas Fr based estimates produced errors up to 55%. The highest errors were associated with the walking gait. The transition between pendular to bouncing gaits fell close to the estimates using relative stride length described for other extant vertebrates. Conversely, the transition from grounded to aerial running appears to be species specific and highly dependent on posture and substrate.

Conclusion
Altogether, this study highlights that using trackways to derive predictions on the locomotor speed and gait, using stride length as the only predictor, are problematic as accurate predictions require information from the animal in question.
Clinicians’ attitudes and perceived barriers and facilitators to cancer treatment clinical practice guideline adherence: a systematic review of qualitative and quantitative literature
Authors: Bierbaum Mia , Rapport Frances , Arnolda Gaston , Nic Giolla Easpaig Brona , Lamprell Klay , Hutchinson Karen , Delaney Geoff P. , Liauw Winston , Kefford Richard , Olver Ian , Braithwaite Jeffrey 
Published: May 2020

Abstract
Background
Clinical Practice Guidelines (CPGs) synthesize the best available evidence to guide clinician and patient decision making. There are a multitude of barriers and facilitators to clinicians adhering to CPGs; however, little is known about active cancer treatment CPG adherence specifically. This systematic review sought to identify clinician attitudes, and perceived barriers and facilitators to active cancer treatment CPG adherence.

Methods
A systematic search was undertaken of five databases; Ovid Medline, PsychInfo, Embase, Scopus, CINAHL, and PROQUEST. The retrieved abstracts were screened for eligibility against inclusion criteria, and a full text review was conducted of all eligible studies. Data were extracted, and a quality assessment was conducted of all included studies. The qualitative papers were thematically analyzed. Attitudes, barriers, and facilitating factors extracted from the quantitative papers were categorized within the qualitative thematic framework.

Results
The search resulted in the identification of 9676 titles. After duplicates were removed, abstracts screened, and full texts reviewed, 15 studies were included. Four themes were identified which related to negative clinician attitudes and barriers to active cancer treatment CPG adherence: (1) concern over CPG content and currency of CPGs; (2) concern about the evidence underpinning CPGs; (3) clinician uncertainty and negative perceptions of CPGs; and (4) organizational and patient factors. The review also identified four themes related to positive attitudes and facilitators to active cancer treatment CPG adherence: (5) CPG accessibility and ease of use; (6) endorsement and dissemination of CPGs and adequate access to treatment facilities and resources; (7) awareness of CPGs and belief in their relevance; and (8) belief that CPGs support decision making, improve patient care, reduce clinical variation, and reduce costs.

Conclusion
These results highlight that adherence to active cancer treatment CPG recommendations by oncology clinicians is influenced by multiple factors such as attitudes, practices, and access to resources. The review has also revealed many similarities and differences in the factors associated with general CPG, and active cancer treatment CPG, adherence. These findings will inform tailored implementation strategies to increase adherence to cancer treatment CPGs.

Trial registration
PROSPERO (2019) CRD42019125748.
Hypofractionated palliative volumetric modulated arc radiotherapy with the Radiation Oncology Study Group 8502 “QUAD shot” regimen for incurable head and neck cancer
Authors: Toya Ryo , Saito Tetsuo , Yamaguchi Kohsei , Matsuyama Tomohiko , Watakabe Takahiro , Matsumoto Tadashi , Yoshida Ryoji , Hirosue Akiyuki , Murakami Daizo , Orita Yorihisa , Nakayama Hideki , Oya Natsuo 
Published: May 2020

Abstract
Background
To review a single institutional experience of the Radiation Therapy Oncology Group (RTOG) 8502 “QUAD shot” regimen using volumetric modulated arc radiotherapy (VMAT) for incurable head and neck cancer (HNC).

Methods
Thirty-four consecutive patients with HNC were treated with at least one cycle of the RTOG 8502 regimen. Treatment plans included the use of VMAT with 6 MV photons generated by a linear accelerator. Two daily fractions of 3.7 Gy were delivered with an interval of at least 6 h for 2 consecutive days, totaling 14.8 Gy over 4 fractions. This was repeated every 3–4 weeks for a total of three cycles. No concurrent systemic therapy was performed.

Results
The number of completed cycles was 1 in 6 (18%) patients, 2 in 5 (15%), and 3 in 23 (68%). Tumor response was achieved in 29 (85%) patients and symptom relief in 20 (77%) of 26 patients. Overall response (tumor response or symptom relief) was achieved in 32 (94%) patients. All patients who received 2 or more treatment cycles achieved overall response. Median overall survival (OS) was 5.7 months. Multivariate analysis revealed that completion of all three treatment cycles was significantly associated with better OS (P = 0.002). Grade 2 toxicity was observed in four (12%) patients, but no acute Grade ≥ 3 or late toxicity was observed.

Conclusions
The RTOG 8502 “QUAD shot” regimen using VMAT is effective for incurable HNC with highly reduced toxicity. Treatment with multiple cycles is recommended for better treatment response and/or survival.
Synovial bone sialoprotein indicates aseptic failure in total joint arthroplasty
Authors: Busch André , Jäger Marcus , Dittrich Florian , Wegner Alexander , Landgraeber Stefan , Haversath Marcel 
Published: May 2020

AbstractBackgroundUntil today, a reliable diagnostic discrimination between periprosthetic joint infections (PJI) and aseptic failure (AF) after total joint arthroplasty (TJA) remains challenging. Nearly all recent research focused on synovial markers to be elevated in PJI rather than in AF patients. In this study, synovial bone sialoprotein (sBSP) was investigated in PJI and AF arthroplasty patients before revision surgery.MethodssBSP and C-reactive protein (CRP) were determined in synovial fluid samples of PJI (n= 13) patients fulfilling the MSIS criteria and AF (n= 25) patients. Beside descriptive analysis and comparison, computed statistics determined the area under the receiver operating characteristics curve (AUC) to evaluate the discrimination ability of the tested synovial markers.ResultsIn patients with PJI according to the MSIS criteria, mean sBSP was significantly lower: 14.8 ng/ml (95% CI 5.5-24.1) vs. 38.2 ng/ml in the AF group (95% CI 31.1-45.3),p≤ 0.001. Conversely, mean sCRP was significantly higher in PJI patients: 8.4 μg/ml (95% CI 0-17.2) vs. 1.8 μg/ml in the AF group (95% CI 0.9-2.8),p= 0.032. The AUC of sCRP in PJI patients was 0.71. The AUC of sBSP in AF revision arthroplasty patients was 0.83. The detection of osteolyses was not associated with higher sBSP concentrations.ConclusionsConsidering the MSIS criteria, significantly higher sBSP concentrations were found in synovial fluid samples of AF compared to PJI patients. sCRP showed only fair, sBSP good discrimination potential. If it is not clear whether PJI is present or not, sBSP may be considered as an add-on synovial marker.
Circ_0008532 promotes bladder cancer progression by regulation of the miR-155-5p/miR-330-5p/MTGR1 axis
Authors: Chen Liang , Yang Xiong , Zhao Jun , Xiong Ming , Almaraihah Raya , Chen Zhaohui , Hou Teng 
Published: May 2020

Abstract
Background
Circular RNAs (circRNAs) have been associated with bladder cancer (BC), but the specific underlying molecular mechanism of their association with BC development has not been fully explored.

Methods
Levels of Circ_0008532, MTGR1 and miR-155-5p/miR-330-5p in bladder cancer cell lines and tissues were determined with quantitative real-time PCR and western blotting assays. In vitro and in vivo assays were performed to investigate the function of circ_0008532 in tumorigenesis in bladder cancer cells. The relationships of Circ_0008532, MTGR1 and miR-155-5p/miR-330-5p were predicted using bioinformatic tools and verified by RNA-FISH, RIP and luciferase assays. The effects of circ_0008532 on the Notch signaling pathway were determined by GSEA analysis and western blotting assay.

Results
We found that circ_0008532 is upregulated in BC cell lines and tissues. Moreover, overexpression of circ_0008532 promotes, and silencing of circ_0008532 inhibits the capacity for invasive in BC cells. In addition, circ_0008532 can directly interact with miR-155-5p and miR-330-5p as an miRNA sponge which mediates the expression of the miR-155-5p/miR-330-5p target gene MTGR1 and downstream Notch signaling.

Conclusions
Circ_0008532 may act as an oncogene in BC through a novel circ_0008532/miR-155-5p, miR-330-5p /MTGR1/Notch pathway axis, which in turn may provide potential biomarkers and a therapeutic target for the management of bladder cancer.