bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mixture survival models methodology: an application to cancer immunotherapy assessment in clinical trials
Authors: Sanchez Lizet , Lorenzo-Luaces Patricia , Fonte Claudia , Lage Agustin 
Published: December 2019

Abstract
Progress in immunotherapy revolutionized the treatment landscape for advanced lung cancer, raising survival expectations beyond those that were historically anticipated with this disease. In the present study, we describe the methods for the adjustment of mixture parametric models of two populations for survival analysis in the presence of long survivors. A methodology is proposed in several five steps: first, it is proposed to use the multimodality test to decide the number of subpopulations to be considered in the model, second to adjust simple parametric survival models and mixture distribution models, to estimate the parameters and to select the best model fitted the data, finally, to test the hypotheses to compare the effectiveness of immunotherapies in the context of randomized clinical trials. The methodology is illustrated with data from a clinical trial that evaluates the effectiveness of the therapeutic vaccine CIMAvaxEGF vs the best supportive care for the treatment of advanced lung cancer. The mixture survival model allows estimating the presence of a subpopulation of long survivors that is 44% for vaccinated patients. The differences between the treated and control group were significant in both subpopulations (population of short-term survival: p = 0.001, the population of long-term survival: p = 0.0002). For cancer therapies, where a proportion of patients achieves long-term control of the disease, the heterogeneity of the population must be taken into account. Mixture parametric models may be more suitable to detect the effectiveness of immunotherapies compared to standard models.
Estimating Optimal Dynamic Treatment Strategies Under Resource Constraints Using Dynamic Marginal Structural Models
Authors: Caniglia Ellen , Murray Eleanor , Hernan Miguel , Shahn Zach 
Published: December 2019

Abstract
Background: Existing methods for estimating the optimal treatment or monitoring strategy typically assume unlimited access to resources. However, when a health system has resource constraints, such as limited funds, access to medication, or monitoring capabilities, medical decisions must balance impacts on both individual and population health outcomes. That is, decisions should account for competition between individuals in resource usage. A simple solution is to estimate the (counterfactual) resource usage under the possible interventions and choose the optimal strategy for which resource usage is within acceptable limits. Methods: We propose a method to identify the optimal dynamic intervention strategy that leads to the best expected health outcome accounting for a health system's resource constraints. We then apply this method to determine the optimal dynamic monitoring strategy for people living with HIV when resource limits on monitoring exist using observational data from the HIV-CAUSAL Collaboration. In our example, we identify the optimal CD4 cell count at which to decrease monitoring frequency from every 3-6 months to every 9-12 months among the subset of strategies that satisfy a hypothetical constraint on monitoring. We find the resource constrained dynamic strategy (RCDS) that minimizes the risk of virologic failure given a hypothetical resource constraint where individuals can only be monitored on average every 6 months. Results: Given the hypothetical resource constraint, the optimal monitoring strategy is "monitor CD4 cell count and HIV-RNA every 3-6 months when CD4 is below 320 cells/ml and every 9-12 months when CD4 is above 320 cells/ml." Conclusions: We describe and and apply a method to identify the optimal RCDS given a hypothetical resource constraint. Similar applications may be useful in settings with limited availability of or capacity for monitoring individuals living with HIV or other chronic diseases.
Development of A Guideline for Reporting Mediation Analyses (AGReMA)
Authors: Cashin Aidan Gregory , McAuley James H , Lamb Sarah E , Hopewell Sally , Kamper Steven J , Williams Christopher M , Henschke Nicholas , Lee Hopin 
Published: December 2019

Abstract
Background There are a growing number of studies using mediation analysis to understand the mechanisms of health interventions and exposures. Recent work has shown that the reporting of these studies is heterogenous and incomplete. This problem stifles clinical application, reproducibility, and evidence synthesis. This paper describes the processes and methods that will be used to develop a guideline for reporting studies of mediation analyses (AGReMA).Methods/Design AGReMA will be developed over five overlapping stages. Stage one will comprise a systematic review to examine relevant evidence on the quality of reporting in published studies that use mediation analysis. In the second stage we will consult a group of methodologists and applied researchers by using a Delphi process to identify items that should be considered for inclusion in AGReMA. The third stage will involve a consensus meeting to consolidate and prioritise key items to be included in AGReMA. The fourth stage will involve production of AGReMA and an accompanying explanation and elaboration document. In the final stage we will disseminate the AGReMA statement via journals, conferences, and professional meetings across multiple disciplines.Discussion The development and implementation of AGReMA will improve the standardization, transparency, and completeness in the reporting of studies that use mediation analysis to understand the mechanisms of health interventions and exposures.
A qualitative study exploring the effects of participation in a community-based pre-operative exercise programme on perceived wellbeing and quality of life in people with newly diagnosed prostate cancer: A pilot study
Authors: Loughney Lisa , McGowan Rachel , O'Malley Kiaran , McCaffrey Noel , Furlong Brona , Walsh Deirdre 
Published: December 2019

Abstract
Purpose: People with a newly diagnosed prostate cancer are often treated by surgery. The time window between cancer diagnosis and surgery causes high levels of uncertainty and stress, which negatively impact quality of life (QoL). This study explored the experience of participating in a community-based pre-operative exercise programme (in the time between cancer diagnosis and surgery) and its impact on perceived wellbeing and QoL in people with newly diagnosed prostate cancer.Methods: Eleven men diagnosed with a new prostate cancer diagnosis were recruited and undertook a prescribed community-based pre-operative exercise training programme in the time available prior to surgery. Following completion of the pre-operative exercise programme (within 1 week before surgery), participants took part in one semi-structured interview which explored four broad QoL domains: physical; psychological; social; and spiritual wellbeing. Data were analysed using thematic analysis (a bottom up/inductive analysis).Results: Data supported four main themes. Participation in the community-based pre-operative exercise training programme (over a mean (SD) of 4 (2) weeks) provided participants with: 1) a teachable moment; 2) a journey of preparation; 3) provided them with a sense of optimism; and 4) social connectedness.Conclusion: This community-based pre-operative exercise training programme enhanced wellbeing and served as an opportunity to improve perceived QoL. Further research is required to explore this in a larger sample.
Identification of the biomarker roles of miR-106 family for predicting the risk and poor survival of colorectal cancer
Authors: Peng Qiliang , Shen Yi , Zhao Peifeng , Cheng Ming , Zhu Yaqun , Xu Bo 
Published: December 2019

Abstract
Background: Recent studies have extensively investigated the roles of miR-106 in colorectal cancer (CRC). However, the associations and molecular mechanism underlying the roles of miR-106 in CRC remain unclear. We aimed to thoroughly investigate the biomarker roles of miR-106 for predicting the risk and survival outcome in CRC.Methods: We first conducted a comprehensive meta-analysis to quantitatively evaluate the roles of miR-106 in the diagnosis and prognosis of CRC. Then, we qualitatively explored the biomarker roles of miR-106 in CRC through an integrative bioinformatics analysis. Results: The results indicated that miR-106 yielded a combined AUC of 0.79 (95% CI: 0.76–0.83), with a pooled sensitivity of 0.50 (95% CI: 0.32–0.68) and a pooled specificity of 0.93 (95% CI: 0.79–0.98) for discriminating CRC cases from normal controls. Moreover, patients with higher expression of miR-106 were significantly associated with shorter disease-free survival (HR: 1.73; 95%CI: 1.23-2.44) and overall survival (HR: 1.39; 95%CI: 1.09-1.77). Finally, gene ontology and pathway analysis demonstrated that miR-106 family was highly involved in the initiation and progression of CRC and indicated the potential molecular mechanism for miR-106 in CRC.Conclusions: Our results indicated that miR-106 showed promising potential as diagnostic and prognostic biomarker for CRC. Nevertheless, the underlying molecular mechanism of miR-106 family involved in CRC requires further investigation.
The Effects of Dog Management on Echinococcus spp. Prevalence in Villages on the Eastern Tibetan Plateau, China
Authors: Xiaodong Weng , Mu Zhiqiang , Wang Xu , Zuo Qingqiu , Ma Shuo , Ding Youzhong , Wang Xiaoming , Wu Weiping , Craig Philip S , Wang Zhenghuan 
Published: December 2019

Abstract
Background The pastoral area of the eastern Tibetan plateau is a very important human echinococcosis endemic region. Domestic dogs are the main definitive host for the transmission of Echinococcus granulosus sensu lato (s.1.) and E. multilocularis to humans. To control the infection risks, a national-level canine echinococcosis prevention and control program has been implemented since 2015 in Shiqu County, Sichuan, China, The objective of this investigation was to evaluate its effect on Echinococcus spp. prevalence in dogs.Methods We surveyed 69 households with 84 owned dogs, for dog keeping information in the villages of Rizha and Eduoma. A total of 105 dog fecal samples, consisting of 75 from owned dogs and 30 unknown dog fecal samples were collected between 2015 and 2017 to determine Echinococcus spp. prevalence using copro-PCR. Eight variables based on household surveys were included into a logistic regression model for significantly relevant factors to canine echinococcosis prevalence in dogs.Results The overall Echinococcus spp. copro-DNA prevalence decreased significantly in dogs from 51.2% (2015) to 20.0% (2017) in Rizha, and insignificantly from 11.5% (2016) to 4.3% (2017) in Eduoma. Echinococcus multilocularis was the most prevalent species continually detected during the entire research period, while E. granulosus was rare and not detected in 2017. Echinococcus shiquicus prevalence was as high as E. multilocularis, although only detected in 2015 in Rizha. Unleashed dog feces were mainly collected in Rizha Village in 2015. Although 93.2% of owned dogs were leashed, and the monthly praziquantel dosing rate reached 97%, E. multilocularis infection could still be detected in 11.1% of owned dogs in 2017. Monthly deworming, leashing dogs all day, and the avoidance of dogs feeding on livestock viscera are significant measures to prevent canine echinococcosis infection in owned dogs.ConclusionCarrying out a canine echinococcosis prevention and control program can significantly decrease the Echinococcus prevalence. The potential contact between leashed dogs and wild small mammals is still a risk to re-infect owned dogs. This study shows that the long term application of regular dog dosing in the vast remote echinococcosis endemic areas of west China is still challenging.
Australia Ae. aegypti mosquitoes are susceptible to a highly divergent and sylvatic dengue virus type 2 strain infection but are unlikely to transmit
Authors: Pickering Paul , Hugo Leon , Devine Gregor J , Aaskov John G , Liu Wenjun 
Published: December 2019

Abstract
Background: Humans are the primary hosts of the dengue virus; However, sylvatic cycles of transmission can occur among non-human primates and human encroachment to forested regions can be a source of emergence of new strains. We reported the isolation of a highly divergent and sylvatic DENV-2 strain (QML22) from a dengue fever patient returning Australia from Borneo. The objective of the present study was to evaluate the vector competence of Australian Ae. aegypti mosquitoes for this virus. Methods: Four-day old mosquitoes from two strains of Ae. aegypti from Queensland, Australia, were feed sheep blood meal containing 108 50% cell culture infectious dose per ml (CCID50/ml) of either QML22 or an Australian epidemic DENV serotype 2 strain (QML16) isolated from a dengue fever patient in 2015. Mosquitoes were maintained at 28°C, 75% relative humidity and sampled at 7, 10 and 14 days post-infection (DPI). Live virions in mosquito bodies (abdomen/thorax), legs and wings and saliva expectorates from individual mosquitoes were quantified using a Cell Culture Enzyme-linked Immunosorbant Assay (CCELISA) to determine infection, dissemination and transmission rates. Findings: The infection and dissemination rates of the sylvatic DENV2 strain, QML22, within mosquitoes were significantly lower than that for QML16. While the titres of virus in the bodies of mosquitoes infected with either of these viruses were similar, titres in legs and wings were significantly lower in mosquitoes infected with QML22 at most time points although they reached similar levels by 14 DPI. QML16 was detected in 16% (n = 25) and 28% (n = 25) of saliva expectorates at 10 and 14 DPI, respectively. In contrast, no virus was detected in the saliva expectorates of QML22 infected mosquitoes. Conclusions: Australia urban/peri-urban Ae.aegypti species are susceptible to infection by the sylvatic and highly divergent DENV-2 virus QML22. However, our results indicate that replication of QML22 is attenuated relative to the contemporary strain QML16 and/or a salivary gland infection or escape barrier acts to prevent infection of saliva, potentially preventing onward transmission of this highly divergent virus in Australia.
miR-147b-modulated expression of vestigial regulates wing development in the bird cherry-oat aphid Rhopalosiphum padi
Authors: Fan YJ , Li XX , Mohammed Abd Allah A. H. , Liu Y , Gao Xiwu 
Published: December 2019

Abstract
Background: Most aphids exhibit wing polyphenism in which wingless and winged morphs produce depending on the population density and host plant quality. Although the influence of environmental factors on wing polyphenism of aphids have been extensively investigated, molecular mechanisms underlining morph differentiation (i.e. wing development /degeneration), one downstream aspect of the wing polyphenism, has been poorly understood.
Results: We examined the expression levels of the twenty genes involved in wing development network, and only vestigial (vg) showed significantly different expression levels in both whole-body and wall-body of third instar nymphs, with 5.4- and 16.14- fold higher expression in winged lines compared to wingless lines, respectively in Rhopalosiphum padi. vg expression was higher in winged lines compared to wingless lines in third, fourth instar nymphs and adults. Larger difference expression was observed in third (21.38-fold) and fourth (20.91-fold) instar nymphs relative to adults (3.12-fold). Suppression of vg using RNAi repressed the wing development of third winged morphs. Furthermore, dual luciferase reporter assay revealed that the miR-147 can target the vg mRNA. Modulation of miR-147b levels by microinjection of its agomir (mimic) decreased vg expression levels and repressed wing development.
Conclusions: Our findings suggest that vg is essential for wing development in R. padi and that miR-147b modulates its expression.
Frazil jam risk assessment for water diversion projects
Authors: Liu Mengkai , Yang Jia , Guan Guanghua 
Published: December 2019

Abstract
Frazil jams are common ice phenomena in rivers in winter and also threaten the safe operation and limit the water conveyancing efficiency of long-distance canal systems in cold regions. In this paper, based on the canal pool conditions from the Fenzhuanghe sluice to the Beijumahe sluice of the Middle Route of the South-to-North Water Diversion Project, the analytic hierarchy process (AHP) and the fault tree principle (FTP) for frazil jam risk assessment are proposed. The risk factors of frazil jams are then identified based on the AHP. Then the probability and consequence severity of frazil jams induced by each risk factor are scored by experts, and the weights of each risk factor are proposed. Finally, risk level and prevention measures are proposed. The results show that there are 20 risk factors for canal frazil jams and the possibility of risk factors is positively correlated with the consequence severity. As yet, experts have not formed a unified view on the frazil jam mechanism of water diversion projects, and the scoring results are highly dependent on expert positions. This paper recommends the FTP as the frazil jam risk evaluation method, and the corresponding frazil jam level of the project is level III.
Antitumor Effect of Zwitterions of Imidazolium Derived from L-methionine in BALB/c Mice with Lymphoma L5178Y
Authors: Vargas-Castro Karen C. , Puebla Pérez Ana M. , Rangel-Salas Irma I. , Delgado-Saucedo Jorge I. , Pelayo-Vázquez José B. , Becerra-Martínez Elvia , Peregrina-Lucano Alejandro A. , Quiñonez-Lopez Raul R. , Soltero-Reynoso Gabriela J. , Cortes-Llamas Sara A. 
Published: December 2019

Background:In the therapy of cancer, several treatments have been designed using nanomaterials, among which gold nanoparticles (AuNPs) have been featured as a promising antitumoral agent. Our research group has developed the synthesis of gold nanoparticles L-AuNPs and D-AuNPs stabilized with zwitterions of imidazolium (L-1 and D-1) derived from L-methionine and D-methionine. Because the stabilizer agent is chiral, we observed through circular dichroism that AuNPs also present chirality; such chirality as well as the fact that the stabilizing agent contains fragments of methionine and imidazolium that are commonly involved in biological processes, opens up the possibility that this system may have biological compatibility. Additionally, the presence of methionine in the stabilizing agent opens the application of this system as a possible antitumor agent because methionine is involved in methylation processes of molecules such as DNA.Objective:The aim of this research is the evaluation of the antitumor activity of gold nanoparticles stabilized with zwitterions of imidazolium (L-AuNPs) derived from L-methionine in the model of BALB/c mice with lymphoma L5178Y.Methods:Taking as a parameter cell density, the evaluation of the inhibitory effect of L-AuNPs was carried out with a series of in vivo tests in BALB/c type mice; three groups of five mice each were formed (Groups 1, 2 and 3); all mice were i.p. inoculated with the lymphoblast murine L5178Y. Group 1 consisted of mice without treatment. In the Groups 2 and 3 the mice were treated with L-AuNPs at 0.3 mg/Kg on days 1, 7 and 14 by orally and intraperitonally respectively.Results:These results show low antitumor activity of these gold nanoparticles (L-NPsAu) but interestingly, the imidazolium stabilizing agent of gold nanoparticle (L-1) displayed promising antitumor activity. On the other hand, the enantiomer of L-1, (D-1) as well as asymmetric imidazole derivate from L-methionine (L-2), do not exhibit the same activity as L-1.Conclusion:The imidazolium stabilizing agent (L-1) displayed promising antitumor activity. Modifications in the structure of L-1 showed that, the stereochemistry (like D-1) and the presence of methionine fragments (like L-2) are determinants in the antitumor activity of this compound.
Anti-Cholinesterase Activity of Chalcone Derivatives: Synthesis, In Vitro Assay and Molecular Docking Study
Authors: Riswanto Florentinus D.O. , Rawa Mira S.A. , Murugaiyah Vikneswaran , Salin Nurul H. , Istyastono Enade P. , Hariono Maywan , Wahab Habibah A. 
Published: December 2019

Background:
Chalcones, originated from natural product, have been broadly studied
their biological activity against various proteins which at the molecular level, are responsible for
the progress of the diseases in cancer (e.g. kinases), inflammation (oxidoreductases), atherosclerosis
(cathepsins receptor), and diabetes (e.g. α-glucosidase).

Objective:
Here we synthesize 10 chalcone derivatives to be evaluated their in vitro enzymatic inhibition
activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE).

Methods:
The synthesis was carried out using Claissen-Schimdt condensation and the in vitro assay
was conducted using Ellman Method.

Results:
Compounds 2b and 4b demonstrated as the best IC50 of 9.3 μM and 68.7 μM respectively,
towards AChE and BChE inhibition. Molecular docking studies predicted that this activity
might be due to the interaction of the chalcones with important amino acid residues in the binding
site of AChE such as SER200 and in that of BChE, such as TRP82, SER198, TRP430, TYR440,
LEU286 and VAL288.

Conclusion:
Chalcone can be used as the scaffold for cholinesterase inhibitor, in particularly either
fluorine or nitro group to be augmented at the para-position of Ring B, whereas the hydrophobic
chain is necessary at the meta-position of Ring B.
A Two-Sided Matching Method for Green Suppliers and Manufacturers with Intuitionistic Linguistic Preference Information
Authors: Wang Lan-lin , Liu Zhi , Zheng Yue-ling , Gu Feng-juan 
Published: December 2019

Purpose:
Due to the existing methodologies on two-sided matching seldom consider the asymmetry, uncertainty and fuzziness of the preference information, this paper aims to develop a methodology for solving the selection process between green suppliers and manufacturers with intuitionistic linguistic numbers.

Methods:
This paper first constructs the evaluation indicators for both sides, which are depicted as intuitionistic linguistic numbers. Subsequently, the authors redefine the intuitionistic linguistic numbers’ expected function based on regret theory. By considering the psychological behaviour of the regret aversion of decision makers, the paper constructs the comprehensive perceived values of decision makers. Furthermore, by maximizing the comprehensive perceived values for the two sides, the multi-objectives matching model is established. In addition, this paper adopts a min-max method to transform the multi-objective optimal model into the single-objective model.

Conclusions:
This paper considers fuzziness and hesitancy of the preference information, and also considering the psychological behaviour of the regret aversion of decision makers, the two-sided matching method proposed by this paper is more validity and effectiveness than existing methods.