bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR-596 activated by EP300 controls the tumorigenesis in epithelial ovarian cancer by declining BRD4 and KPNA4
Authors: Wang Deying , Cui Yulan , Xu Aili , Zhao Lin , Li Peiling 
Published: September 2020

AbstractBackgroundEpithelial ovarian cancer (EOC), a subclass of ovarian cancer (OC), is usually diagnosed at advanced stages due to the lack of effective screening means. Mounting reports have disclosed the vitally important roles of microRNAs (miRNAs) in carcinogenesis. Here, we aimed to find out possible miRNAs participating in EOC development.MethodsqRT-PCR ad western blot respectively examined the mRNA and protein levels of studied genes. CCK-8, colony formation, flow cytometry, TUNEL and spheroid formation assays were appropriately employed for examining cell proliferation, cell cycle, apoptosis and stemness. The interaction between molecules was affirmed by luciferase reporter, RNA pull down and ChIP assays.ResultsIn consistent with the observation of a past study, miR-596 expression was relatively low in EOC cells. Up-regulating miR-596 suppressed EOC cell proliferation and stemness. EP300 transcriptionally activated miR-596 to serve as a tumor-repressor in EOC. Then BRD4 and KPNA4, whose knockdown led to restraining effects on cell growth and stemness, were both revealed to be targeted by miR-596 in EOC. Lastly, rescue assays affirmed the tumor-restraining role of miR-596-BRD4/KPNA4 axis in EOC.ConclusionEP300-activated miR-596 hampered cell growth and stemness via targeting BRD4 and KPNA4 in EOC, proofing miR-596 as a promising therapeutic target in treating EOC patients.
The crosstalk between circular RNAs and the tumor microenvironment in cancer metastasis
Authors: Shao Ying , Lu Bingjian 
Published: September 2020

Abstract
Background
Carcinomas are highly heterogeneous with regard to various cancer cells within a tumor microenvironment (TME), which is composed of stromal cells, blood vessels, immunocytes, and modified extracellular matrix.

Focus of the study
Circular RNAs (circRNAs) are non-coding RNAs that are expressed in cancer and stromal cells. They are closely associated with cancer metastasis as their expression in tumor cells directs the latter to migrate to different organs. circRNAs packaged in exosomes might be involved in this process. This is particularly important as the TME acts in tandem with cancer cells to enhance their proliferation and metastatic capability. In this review, we focus on recent studies on the crosstalk between circRNAs and the TME during cancer metastasis.

Conclusion
We particularly emphasize the roles of the interaction between circRNAs and the TME in anoikis resistance, vessel co-option, and local circRNA expression in directing homing of exosome.
Effectiveness of peer-learning assisted primary school students educating the rural community on insecticide-treated nets utilization in Jimma-zone Ethiopia
Authors: Kebede Yohannes , Abebe Lakew , Alemayehu Guda , Sudhakar Morankar , Birhanu Zewdie 
Published: September 2020

AbstractBackgroundMaking insecticide-treated nets (ITNs) utilization a social norm would support the global goal of malaria eradication and Ethiopian national aim of its elimination by 2030. Jimma zone is one of the endemic settings in Ethiopia. This study aimed to report effects of malaria education, delivered by students, on community behaviours; particularly ITNs.MethodsIn pre-posttest, cross-sectional household surveys conducted in rural villages of 5 districts in Jimma Zone, Ethiopia, 762 households were sampled. The intervention engaged students from primary schools in participatory peer education within small groups, followed by exposing parents with malaria messages aimed at influencing perceptions and practices. The data were analysed using SPSS version 20.0. Proportions/means differences were computed to compare changes in exposure, knowledge, perceptions, and practices using 95% CI at p < 0.05. Regression analyses were conducted to assess exposures to school-based education, content intensity, perception, and access related predictors of ITN utilization over the intervention periods.ResultsOver the intervention periods, the findings showed significant improvement in exposure to and content intensity of malaria messages delivered by students, effect size (ES) = 44.5% and 19.3%, p < 0.001, respectively. ITN utilization (ES = 25.8%), and the reported behaviour of giving ITN priority to children under 5 years old and pregnant women increased by ES = 16.3% and  24.8%, respectively. The exposure status or content intensity of malaria education, in turn, significantly improved comprehensive knowledge about malaria (β = +1.82), misconceptions about causes (β = − 11.46), awareness of caring for ITN (β = +24.79), identifying ITN as effective preventive methods (OR = 1.93), attitude towards ITN (β = +0.20), perceived efficacy of ITN (OR = 1.04), acceptance of ITN as a means to control the danger of malaria (β = +8.08%), and ITN utilization (OR = 1.85). Nonetheless, perceived threat (β = − 0.19) significantly negatively correlated with exposure to students’ messages. Socio-demography, access, exposures to messages, and parental perception that students were good reminders predicted ITN utilization over the intervention periods with some changing patterns.ConclusionsExposing the community to malaria education through students effectively supports behaviour change, particularly ITN usage, to be more positive towards desired malaria control practices. A school-based strategy is recommended to the national effort to combat malaria.
A family of partial-linear single-index models for analyzing complex environmental exposures with continuous, categorical, time-to-event, and longitudinal health outcomes
Authors: Wang Yuyan , Wu Yinxiang , Jacobson Melanie H. , Lee Myeonggyun , Jin Peng , Trasande Leonardo , Liu Mengling 
Published: September 2020

AbstractBackgroundStatistical methods to study the joint effects of environmental factors are of great importance to understand the impact of correlated exposures that may act synergistically or antagonistically on health outcomes. This study proposes a family of statistical models under a unified partial-linear single-index (PLSI) modeling framework, to assess the joint effects of environmental factors for continuous, categorical, time-to-event, and longitudinal outcomes. All PLSI models consist of a linear combination of exposures into a single index for practical interpretability of relative direction and importance, and a nonparametric link function for modeling flexibility.MethodsWe presented PLSI linear regression and PLSI quantile regression for continuous outcome, PLSI generalized linear regression for categorical outcome, PLSI proportional hazards model for time-to-event outcome, and PLSI mixed-effects model for longitudinal outcome. These models were demonstrated using a dataset of 800 subjects from NHANES 2003–2004 survey including 8 environmental factors. Serum triglyceride concentration was analyzed as a continuous outcome and then dichotomized as a binary outcome. Simulations were conducted to demonstrate the PLSI proportional hazards model and PLSI mixed-effects model. The performance of PLSI models was compared with their counterpart parametric models.ResultsPLSI linear, quantile, and logistic regressions showed similar results that the 8 environmental factors had both positive and negative associations with triglycerides, with a-Tocopherol having the most positive and trans-b-carotene having the most negative association. For the time-to-event and longitudinal settings, simulations showed that PLSI models could correctly identify directions and relative importance for the 8 environmental factors. Compared with parametric models, PLSI models got similar results when the link function was close to linear, but clearly outperformed in simulations with nonlinear effects.ConclusionsWe presented a unified family of PLSI models to assess the joint effects of exposures on four commonly-used types of outcomes in environmental research, and demonstrated their modeling flexibility and effectiveness, especially for studying environmental factors with mixed directional effects and/or nonlinear effects. Our study has expanded the analytical toolbox for investigating the complex effects of environmental factors. A practical contribution also included a coherent algorithm for all proposed PLSI models with R codes available.
Maternal urinary concentrations of organophosphate ester metabolites: associations with gestational weight gain, early life anthropometry, and infant eating behaviors among mothers-infant pairs in Rhode Island
Authors: Crawford Kathryn A. , Hawley Nicola , Calafat Antonia M. , Jayatilaka Nayana K. , Froehlich Rosemary J. , Has Phinnara , Gallagher Lisa G. , Savitz David A. , Braun Joseph M. , Werner Erika F. , Romano Megan E. 
Published: September 2020

AbstractBackgroundOrganophosphate esters (OPEs)—used as flame retardants and plasticizers—are associated with adverse pregnancy outcomes such as reduced fecundity and live births and increased preterm delivery. OPEs may interfere with growth and metabolism via endocrine-disruption, but few studies have investigated endocrine-related outcomes. The objective of this pilot study (n = 56 mother-infant pairs) was to evaluate associations of OPEs with gestational weight gain (GWG), gestational age at delivery, infant anthropometry, and infant feeding behaviors.MethodsWe quantified OPE metabolites (bis-2-chloroethyl phosphate [BCEP], bis (1,3-dichloro-2-propyl) phosphate [BDCPP], diphenyl phosphate [DPHP]) in pooled maternal spot urine collected throughout pregnancy (~ 12, 28, and 35 weeks’ gestation). We obtained maternal sociodemographic characteristics from questionnaires administered at enrollment and perinatal characteristics from medical record abstraction. Trained research assistants measured infant weight, length, head and abdominal circumferences, and skinfold thicknesses at birth and 6 weeks postpartum. Mothers reported infant feeding behavior via the Baby Eating Behavior Questionnaire (BEBQ). Using multiple linear regression, we assessed associations of log2-transformed maternal urinary OPE metabolites with GWG, gestational age at delivery, infant anthropometry at birth, weekly growth rate, and BEBQ scores at 6 weeks postpartum. We used linear mixed effects (LME) models to analyze overall infant anthropometry during the first 6 weeks of life. Additionally, we considered effect modification by infant sex.ResultsWe observed weak positive associations between all OPE metabolites and GWG. In LME models, BDCPP was associated with increased infant length (β = 0.44 cm, 95%CI = 0.01, 0.87) and weight in males (β = 0.14 kg, 95%CI = 0.03, 0.24). BDCPP was also associated with increased food responsiveness (β = 0.23, 95%CI = 0.06, 0.40). DPHP was inversely associated with infant abdominal circumference (β = − 0.50 cm, 95%CI = − 0.86, − 0.14) and female weight (β = − 0.19 kg, 95%CI = − 0.36, − 0.02), but positively associated with weekly growth in iliac skinfold thickness (β = 0.10 mm/wk., 95%CI = 0.02, 0.19). Further, DPHP was weakly associated with increased feeding speed. BCEP was associated with greater infant thigh skinfold thickness (β = 0.34 mm, 95%CI = 0.16, 0.52) and subscapular skinfold thickness in males (β = 0.14 mm, 95%CI = 0.002, 0.28).ConclusionsCollectively, these findings suggest that select OPEs may affect infant anthropometry and feeding behavior, with the most compelling evidence for BDCPP and DPHP.
Overcoming immunotherapy resistance in non-small cell lung cancer (NSCLC) - novel approaches and future outlook
Authors: Horvath Lena , Thienpont Bernard , Zhao Liyun , Wolf Dominik , Pircher Andreas 
Published: September 2020

AbstractImmunotherapy (IO) has revolutionized the therapy landscape of non-small cell lung cancer (NSCLC), significantly prolonging the overall survival (OS) of advanced stage patients. Over the recent years IO therapy has been broadly integrated into the first-line setting of non-oncogene driven NSCLC, either in combination with chemotherapy, or in selected patients with PD-L1highexpression as monotherapy. Still, a significant proportion of patients suffer from disease progression. A better understanding of resistance mechanisms depicts a central goal to avoid or overcome IO resistance and to improve patient outcome.We here review major cellular and molecular pathways within the tumor microenvironment (TME) that may impact the evolution of IO resistance. We summarize upcoming treatment options after IO resistance including novel IO targets (e.g. RIG-I, STING) as well as interesting combinational approaches such as IO combined with anti-angiogenic agents or metabolic targets (e.g. IDO-1, adenosine signaling, arginase). By discussing the fundamental mode of action of IO within the TME, we aim to understand and manage IO resistance and to seed new ideas for effective therapeutic IO concepts.
Assessing mental well-being in a Sinhala speaking Sri Lankan population: validation of the WHO-5 well-being index
Authors: Perera B. P. R. , Jayasuriya R. , Caldera A. , Wickremasinghe A. R. 
Published: September 2020

Abstract
Purpose
The WHO-5 well-being index is a widely used, short rating scale that measures subjective well-being. We translated the WHO-5 index into Sinhala and tested its psychometric properties including measurement invariance among diverse groups in a community sample in Sri Lanka.

Methods
The sample of 267 persons aged between 16 and 75 years was recruited from a semi-urban area. 219 completed a paper-based questionnaire and 48 responded to an online survey. Construct validity was tested for factorial validity (Confirmatory Factor Analysis -CFA), convergent validity and known group validity. Composite reliability for congeneric measures and test-retest reliability were also tested. Multi-group CFA (MG-CFA) was used to test measurement invariance.

Results
The translated Sinhala version demonstrated good content and face validity. Internal consistency reliability of the five items had a Cronbach’s alpha of 0.85 and test-retest reliability over 2 weeks was satisfactory (Pearson r = 0.72, p < 0.001, ICC = 0.82). Confirmatory factor analysis supported factorial validity with a $$ {\chi}_5^2 $$

χ

5
2

=4.99 (p = 0.28), a RMSEA of 0.03 (90% C.I. =0.00–0.10), a SRMR of 0.02, a TLI of 0.99 and a CFI of 0.99; factor loadings were between 0.55 and 0.89. Measurement invariance was acceptable for configural, metric and scalar invariance for gender.
WHO-5 scores were significantly negatively correlated with the Patient Health Questionnaire (PHQ-9) (Pearson’s r = − 0.45, p < 0.001) scores and the Kessler Psychological Distress Scale (K10) scores (Pearson’s r = − 0.56, p < 0.001).

Conclusion
The Sinhala translation of WHO-5 well-being index has shown acceptable psychometric properties and can be used for assessing mental well-being in the community in Sri Lanka. Further testing of the measure with larger and diverse (including different ethnic/cultural) groups are indicated to test measurement invariance of the measure.
What should community organisations consider when deciding to partner with researchers? A critical reflection on the Zilla Budakattu Girijana Abhivrudhhi Sangha experience in Karnataka, India
Authors: Pratt Bridget , Seshadri Tanya , Srinivas Prashanth N. 
Published: September 2020

Abstract
Background
Community organisations and community members are increasingly being involved in health research projects worldwide as part of the engagement movement. Achieving deeper forms of community engagement like partnership demands that decision-making power be shared with community partners. However, how can community partners assess if meaningful engagement and shared decision-making will be possible when approached by prospective research partners? In this paper, we explore how community organisations decide to join health research projects when approached by health researchers.

Methods
Case study research was undertaken on a health systems research project in Karnataka, India called Participation for Local Action, which was carried out by local researchers in partnership with the Zilla Budakattu Girijana Abhivrudhhi Sangha, a community development organisation. In-depth interviews were conducted with the researchers, Sangha leaders and field investigators from their community.

Results
Thematic analysis identified two main themes – ‘context’ and ‘deciding to engage’. The Sangha’s experience offers lessons to other community organisations that can help them when deciding to engage with researchers in terms of what features to look for in research partners and in proposed research projects, what requests to make of prospective research partners, and what sorts of outcomes or partnership agreements to accept. These lessons may be especially applicable in contexts where relationships of trust already exist between partners and where they have the skills to lead data collection and analysis.

Conclusions
We hope that this guidance will help empower community organisations to select good research partners and promote more equitable partnerships between community partners and academic researchers.
Users with spinal cord injury experience of robotic Locomotor exoskeletons: a qualitative study of the benefits, limitations, and recommendations
Authors: Kinnett-Hopkins Dominique , Mummidisetty Chaithanya K. , Ehrlich-Jones Linda , Crown Deborah , Bond Rachel A. , Applebaum Marc H. , Jayaraman Arun , Furbish Catherine , Forrest Gail , Field-Fote Edelle , Heinemann Allen W. 
Published: September 2020

Abstract
Background
Persons with spinal cord injury (SCI) may experience both psychological and physiological benefits from robotic locomotor exoskeleton use, and knowledgeable users may have valuable perspectives to inform future development. The objective of this study is to gain insight into the experiences, perspectives, concerns, and suggestions on the use of robotic locomotor exoskeletons by civilians and veterans living with SCI.

Methods
Participants reported their demographic characteristics and the extent of robotic exoskeleton use in an online survey. Then, 28 experienced robotic locomotor exoskeleton users participated in focus groups held at three regional hospitals that specialize in rehabilitation for persons with SCI. We used a qualitative description approach analysis to analyze the data, and included thematic analysis.

Results
Participants expressed that robotic exoskeletons were useful in therapy settings but, in their current form, were not practical for activities of daily living due to device limitations. Participants detailed the psychological benefits of being eye-level with their non-disabled peers and family members, and some reported physiologic improvements in areas such as bowel and bladder function. Participants detailed barriers of increased fatigue, spasticity, and spasms and expressed dissatisfaction with the devices due to an inability to use them independently and safely. Participants provided suggestions to manufacturers for technology improvements.

Conclusions
The varied opinions and insights of robotic locomotor exoskeletons users with SCI add to our knowledge of device benefits and limitations.
The FCTC dilemma on heated tobacco products
Authors: Gruszczynski Lukasz , Melillo Margherita 
Published: September 2020

Abstract
Background
In October 2018, the Conference of the Parties of the Framework Convention on Tobacco Control (FCTC or Convention) adopted its first decision on novel and emerging tobacco products, including heated tobacco products (HTPs). The decision remains ambiguous, e.g. by making a distinction between tobacco sticks and HTP devices. Against this background, the article seeks to answer two interrelated questions: whether and to what extent HTPs are covered by the FCTC, and whether regime provided by the Convention is suitable for their regulation.

Results
HTPs need to be classified under the FCTC as tobacco products. The distinction made by the Conference of the Parties between sticks and devices leads however to unsatisfactory results as it creates loopholes in tobacco control standards existing at the international level. A better approach, as argued in this article, is to conceptualize the notion of ‘tobacco products’ in functional terms as a combination of both a device and stick.
While subjecting HTPs to all FCTC disciplines is, in light of our current scientific knowledge, a rational approach, such classification can be modified in the future once a sufficient amount of new evidence on their risk profile is collected. Any decision on the optimal regulatory model for HTPs will need to take into account not only health risks and potential benefits for individual users, but also the specific systemic concerns (e.g. HTPs as a gateway product). The state of scientific research is however not the only factor that will determine the fate of HTPs under the Convention. What is equally important is a conceptualization of the FCTC’s objectives. If a complete eradication of the tobacco epidemic is the ultimate goal, reduced levels of risk may not be enough to justify the different (i.e. more lenient) regulatory regime for HTPs.

Conclusions
The Conference of the Parties should clarify the definition of tobacco products in light of recent changes in the market. When designing the regulatory regime for HTPs under the FCTC in the future, one has to consider not only scientific evidence but also pay attention to the objective of the Convention (or more generally to the values that underlie the current tobacco control paradigm).
Fermentation of Danggui Buxue Tang, an ancient Chinese herbal mixture, together with Lactobacillus plantarum enhances the anti-diabetic functions of herbal product
Authors: Guo Rui , Guo Shuchen , Gao Xiong , Wang Huaiyou , Hu Weihui , Duan Ran , Dong Tina T. X. , Tsim Karl W. K. 
Published: September 2020

AbstractBackgroundDanggui Buxue Tang (DBT), an ancient Chinese herbal decoction containing Astragali Radix and Angelicae Sinensis Radix at a ratio of 5: 1, is prescribed for menopausal women. Flavonoids and its flavonoid glycosides are considered as the major active ingredients within the herbal decoction; however, their amount is not controllable during the preparation. Besides, the aglycons within DBT are believed to have better gut absorption and pharmacological efficacy.MethodsThe herbal extract of DBT was fermented withLactobacillus plantarum. The amounts of flavonoid glucosides and its aglycones in the fermented product were analyzed by using UPLC-MS/MS. In addition, in vitro assays were employed to evaluate the efficacy of the fermented DBT in regulating the activities of α-glucosidase, α-amylase and lipase, as well as their antioxidant capacity (DPPH and T-AOC assays) and anti-glycation property (BSA-methylglyoxal, BSA-fructose, and arginine-methylglyoxal models).ResultsThe fermentation of DBT withL. plantarumdrove a completed conversion of calycosin-7-O-β-D-glucoside and ononin to calycosin and formononetin, respectively. The chemical transformation could be probably mediated by β-glycosidase within the fermented product. Several in vitro assays corresponding to anti-diabetic functions were compared between parental DBT against its fermented product, which included the activities against α-glucosidase, α-amylase and lipase, as well as anti-oxidation and anti-glycation. The fermented DBT showed increased activities in inhibiting α-glycosidase, suppressing DPPH radical-scavenging and anti-glycation, as compared to the original herbal product.ConclusionThese results suggested that DBT being fermented with the probioticL. plantarumcould pave a new direction for fermentation of herbal extract, as to strengthen its pharmacological properties in providing health benefits.