bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using life course charts to assess and compare trajectories of amphetamine type stimulant consumption in different user groups: a cross-sectional study
Authors: Martens Marcus-Sebastian , Zurhold Heike , Rosenkranz Moritz , O’Donnell Amy , Addison Michelle , Spencer Liam , McGovern William , Gabrhelík Roman , Petruželka Benjamin , Rowicka Magdalena , Liebregts Nienke , Degkwitz Peter , Kaner Eileen , Verthein Uwe 
Published: January 2020

Abstract
Background
Amphetamine-type stimulants (ATS) are the second most commonly used illicit drugs in Europe and globally. However, there is limited understanding of what shapes patterns of ATS use over the life course. The ATTUNE project “Understanding Pathways to Stimulant Use: a mixed methods examination of the individual, social and cultural factors shaping illicit stimulant use across Europe” aims to fill this gap. Here we report initial findings from the life course chart exercise conducted as part of qualitative interviews with ATS users and nonusers.

Methods
Two hundred seventy-nine in-depth qualitative interviews were conducted with five ATS user groups (current and former dependent users;current and former frequent users;non-frequent users) and one group of exposed non-ATS users in five European countries (Germany, UK, Poland, Netherlands and Czech Republic). As part of the interviews, we used life course charts to capture key life events and substance use histories. Life events were categorised as either positive, neutral or negative, and associated data were analysed systematically to identify differences between user groups. We applied statistical analysis of variance (ANOVA) and analysis of covariance (ANCOVA) to test for group differences.

Results
Out of 3547 life events documented, 1523 life events were categorised as neutral, 1005 life events as positive and 1019 life events as negative. Current and formerly dependent ATS users showed more negative life events for the entire life course after age adjustment. Although some group differences could be attributed to the individuals’ life course prior to first ATS use, most negative life events were associated with periods of ATS usage. A detailed analysis of the specific life domains reveals that dominantly, the social environment was affected by negative life events.

Conclusions
For non-dependent, frequent and non-frequent ATS users, negative life events from the period of ATS use do not become obvious in our analysed data. Besides preventing a pathway into ATS dependency, the aim of an intervention should be to reduce the harm by for example drug testing which offers also the opportunity for interventions to prevent developing a substance use dependency.
For the group of dependent ATS users, our study suggests holistic, tailored interventions and specialist treatment services are needed, as a single, simple intervention is unlikely to cover all the life domains affected.
Albumin-fibrinogen ratio and fibrinogen-prealbumin ratio as promising prognostic markers for cancers: an updated meta-analysis
Authors: Sun Da-wei , An Lin , Lv Guo-yue 
Published: January 2020

Abstract
Objective
Provide an updated and comprehensive evaluation of the prognostic value of the albumin-fibrinogen ratio (AFR) and the fibrinogen-prealbumin ratio (FPR) for patients with cancer.

Materials and methods
Four databases (PubMed, Web of Science, Cochrane Library, and WanFang) were searched. The primary endpoints were overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). Pooled data were synthesized using StataMP 14 and expressed as hazard ratios (HRs) and 95% confidence intervals (CIs).

Results
This update examined 19 studies (7282 cases) that assessed the correlation of AFR with cancer prognosis. Pooled univariate and multivariate analyses indicated significant correlations of low AFR with poor OS (HR 2.18, 95%CI 1.87–2.55 and HR 1.75, 95%CI 1.54–2.00, respectively), poor DFS (HR 1.89, 95%CI 1.54–2.32 and HR 1.51, 95%CI 1.29–1.76, respectively), and poor PFS (HR 1.68, 95%CI 1.42–1.99 and HR 1.48, 95%CI 1.16–1.88, respectively). Pooled univariate and multivariate analyses of 6 studies (2232 cases) indicated high FPR significantly correlated with poor OS (HR 2.37, 95%CI 2.03–2.77 and HR 1.97, 95%CI 1.41–2.77, respectively). One study reported that high FPR correlated with poor DFS (univariate analysis: HR 2.20, 95%CI 1.35–3.57; multivariate analysis: HR 1.77, 95%CI 1.04–2.99) and one study reported a correlation of high FPR with poor PFS in univariate analysis alone (HR 1.79, 95%CI 1.11–2.88).

Conclusion
A low AFR and a high FPR correlated with increased risk of cancer mortality and recurrence. AFR and FPR may be promising prognostic markers for cancers.
Integrating evidence from research into decision-making for controlling endemic tropical diseases in South East Nigeria: perceptions of producers and users of evidence on barriers and solutions
Authors: Ezenwaka Uchenna , Mbachu Chinyere , Etiaba Enyi , Uzochukwu Benjamin , Onwujekwe Obinna 
Published: January 2020

Abstract
Background
Endemic tropical diseases (ETDs) constitute a significant health burden in resource-poor countries. Weak integration of research evidence into policy and practice poses a major challenge to the control of ETDs. This study was undertaken to explore barriers to the use of research evidence in decision-making for controlling ETDs. It also highlights potential strategies for addressing these barriers, including the gaps in research generation and utilisation in the context of endemic disease control.

Methods
Information on barriers and solutions to integrating research evidence into decision-making for controlling ETDs in Anambra State, Nigeria, was collected from 68 participants (producers and users of evidence) during structured discussions in a workshop. Participants were purposively selected and allocated to groups based on their current involvement in endemic disease control and expertise. Discussions were facilitated with a topic guide and detailed notes were taken by an appointed recorder. Outputs from the discussions were synthesised and analysed manually.

Results
Cross-cutting barriers include a weak research linkage between producers and users of evidence and weak capacity to undertake health policy and systems research (HPSR). Producers of evidence were purported to conceptualise and frame their research questions based on their academic interests and funders’ focus without recourse to the decision-makers. Conversely, poor demand for research evidence was reported among users of evidence. Another user barrier identified was moribund research units of the Department of Planning Research and Statistics within the State Ministry of Health. Potential solutions for addressing these barriers include creation of knowledge networks and partnerships between producers and users of evidence, institutionalisation of sustainable capacity-building of both parties in HPSR and revival of State research units.

Conclusions
Evidence-informed decision-making for controlling ETDs is limited by constraints in the interactions of some factors between the users (supply side) and producers (demand side) of evidence. These constraints could be solved through stronger research collaborations, institutionalisation of HPSR, and frameworks for getting research into policy and practice.
Methods to promote equity in health resource allocation in low- and middle-income countries: an overview
Authors: Love-Koh James , Griffin Susan , Kataika Edward , Revill Paul , Sibandze Sibusiso , Walker Simon 
Published: January 2020

AbstractUnfair differences in healthcare access, utilisation, quality or health outcomes exist between and within countries around the world. Improving health equity is a stated objective for many governments and international organizations. We provide an overview of the major tools that have been developed to measure, evaluate and promote health equity, along with the data required to operationalise them.Methods are organised into four key policy questions facing decision-makers: (i) what is the current level of inequity in health; (ii) does government health expenditure benefit the worst-off; (iii) can government health expenditure more effectively promote equity; and (iv) which interventions provide the best value for money in reducing inequity.Benefit incidence analysis can be used to estimate the distribution of current public health sector expenditure, with geographical resource allocation formulae and health system reform being the main government policy levers for improving equity. Techniques from the economic evaluation literature, such as extended and distributional cost-effectiveness analysis can be used to identify ‘best buy’ interventions from a health equity perspective. A range of inequality metrics, from gap measures and slope indices to concentration indices and regression analysis, can be applied to these approaches to evaluate changes in equity.Methods from the economics literature can provide policymakers with a toolkit for addressing multiple aspects of health equity, from outcomes to financial protection, and can be adapted to accommodate data commonly available in low- and middle-income settings.
Gli promotes tumor progression through regulating epithelial-mesenchymal transition in non–small-cell lung cancer
Authors: Jiang Long , Huang Jia , Hu Yingjie , Lu Peiji , Luo Qingquan , Wang Lei 
Published: January 2020

Abstract
Introduction
Lung cancer is the leading causes of cancer-related deaths globally. The most frequent histologic type of lung cancer is non–small-cell lung cancer (NSCLC). NSCLC often undergo epithelial-mesenchymal transition (EMT). The components that control this process are thus promising therapeutic targets.

Materials and methods
Gli/EMT protein expression levels were examined by western blot in paired NSCLC patient tissues and NSCLC cell lines. Functional analyses were performed to investigate SHH/Gli signaling and EMT in NSCLC cell lines. MTS cell viability, luciferase reporter, and western blot assays were performed to analyze pathway activity, while wound healing and transwell assays were executed to measure cell migration and invasion.

Results
Higher Gli1 expressions were detected in tumor samples than in paired normal tissues. Differential expression of EMT biomarkers and activation of p-AKT were observed in tumor tissues. N-Shh stimulation of cells significantly increased reporter activity in NSCLC cell lines, while Gli-i treatment of transfected cells showed less relative reporter activity. When subjected to both Gli-i and N-Shh treatment, NSCLC cell lines continued to demonstrate decreased Gli transcriptional activity. Gli inhibition is associated with decreased expression level of p-AKT, N-cadherin and Vimentin. Knockdown of both Gli1 and Gli2 showed decreased EMT, migrative and invasive ability. Cells stimulated by N-Shh demonstrated greater mobility. In addition, AKT-i treated cells also demonstrated inhibited EMT activity.

Conclusions
This study provides evidence for aberrant upregulation of the Gli signaling pathway and a strong association between expression of Gli versus AKT and EMT markers in NSCLC.
C3a-C3aR signaling promotes breast cancer lung metastasis via modulating carcinoma associated fibroblasts
Authors: Shu Chi , Zha Haoran , Long Haixia , Wang Xinxin , Yang Fei , Gao Jianbao , Hu Chunyan , Zhou Li , Guo Bo , Zhu Bo 
Published: January 2020

AbstractBackgroundMounting evidence suggests that complement components promote tumor progression via modulating immune suppression, angiogenesis, or tumor cell proliferation. However, the role of C3a-C3aR signaling in regulating lung metastasis of breast cancer remains unknown.MethodsWe performed various ex-vivo and in-vivo assays. Genetic and pharmacological C3aR blockade models were applied to investigate the role of C3a-C3aR in metastasis of breast cancer.ResultsC3a-C3aR signaling in CAFs facilitates the metastasis of breast cancer. Mechanically, C3a-C3aR signaling augments pro-metastatic cytokine secretion and extracellular matrix components expression of CAFs via the activation of PI3K-AKT signaling. Genetic or pharmacological blockade of C3aR signaling effectively inhibited lung metastasis of breast cancer in mouse models.ConclusionsC3a-C3aR signaling in CAFs facilitates the metastasis of breast cancer. Targeting C3aR signaling is a potential anti-metastasis strategy for breast cancer therapy.
Identification and transfer of spatial transcriptomics signatures for cancer diagnosis
Authors: Yoosuf Niyaz , Navarro José Fernández , Salmén Fredrik , Ståhl Patrik L. , Daub Carsten O. 
Published: January 2020

Abstract
Background
Distinguishing ductal carcinoma in situ (DCIS) from invasive ductal carcinoma (IDC) regions in clinical biopsies constitutes a diagnostic challenge. Spatial transcriptomics (ST) is an in situ capturing method, which allows quantification and visualization of transcriptomes in individual tissue sections. In the past, studies have shown that breast cancer samples can be used to study their transcriptomes with spatial resolution in individual tissue sections. Previously, supervised machine learning methods were used in clinical studies to predict the clinical outcomes for cancer types.

Methods
We used four publicly available ST breast cancer datasets from breast tissue sections annotated by pathologists as non-malignant, DCIS, or IDC. We trained and tested a machine learning method (support vector machine) based on the expert annotation as well as based on automatic selection of cell types by their transcriptome profiles.

Results
We identified expression signatures for expert annotated regions (non-malignant, DCIS, and IDC) and build machine learning models. Classification results for 798 expression signature transcripts showed high coincidence with the expert pathologist annotation for DCIS (100%) and IDC (96%). Extending our analysis to include all 25,179 expressed transcripts resulted in an accuracy of 99% for DCIS and 98% for IDC. Further, classification based on an automatically identified expression signature covering all ST spots of tissue sections resulted in prediction accuracy of 95% for DCIS and 91% for IDC.

Conclusions
This concept study suggest that the ST signatures learned from expert selected breast cancer tissue sections can be used to identify breast cancer regions in whole tissue sections including regions not trained on. Furthermore, the identified expression signatures can classify cancer regions in tissue sections not used for training with high accuracy. Expert-generated but even automatically generated cancer signatures from ST data might be able to classify breast cancer regions and provide clinical decision support for pathologists in the future.
Nutrient-wide association study of 92 foods and nutrients and breast cancer risk
Authors: Heath Alicia K. , Muller David C. , van den Brandt Piet A. , Papadimitriou Nikos , Critselis Elena , Gunter Marc , Vineis Paolo , Weiderpass Elisabete , Fagherazzi Guy , Boeing Heiner , Ferrari Pietro , Olsen Anja , Tjønneland Anne , Arveux Patrick , Boutron-Ruault Marie-Christine , Mancini Francesca Romana , Kühn Tilman , Turzanski-Fortner Renée , Schulze Matthias B. , Karakatsani Anna , Thriskos Paschalis , Trichopoulou Antonia , Masala Giovanna , Contiero Paolo , Ricceri Fulvio , Panico Salvatore , Bueno-de-Mesquita Bas , Bakker Marije F. , van Gils Carla H. , Olsen Karina Standahl , Skeie Guri , Lasheras Cristina , Agudo Antonio , Rodríguez-Barranco Miguel , Sánchez Maria-José , Amiano Pilar , Chirlaque María-Dolores , Barricarte Aurelio , Drake Isabel , Ericson Ulrika , Johansson Ingegerd , Winkvist Anna , Key Tim , Freisling Heinz , His Mathilde , Huybrechts Inge , Christakoudi Sofia , Ellingjord-Dale Merete , Riboli Elio , Tsilidis Konstantinos K. , Tzoulaki Ioanna 
Published: January 2020

AbstractBackgroundSeveral dietary factors have been reported to be associated with risk of breast cancer, but to date, unequivocal evidence only exists for alcohol consumption. We sought to systematically assess the association between intake of 92 foods and nutrients and breast cancer risk using a nutrient-wide association study.MethodsUsing data from 272,098 women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we assessed dietary intake of 92 foods and nutrients estimated by dietary questionnaires. Cox regression was used to quantify the association between each food/nutrient and risk of breast cancer. A false discovery rate (FDR) of 0.05 was used to select the set of foods and nutrients to be replicated in the independent Netherlands Cohort Study (NLCS).ResultsSix foods and nutrients were identified as associated with risk of breast cancer in the EPIC study (10,979 cases). Higher intake of alcohol overall was associated with a higher risk of breast cancer (hazard ratio (HR) for a 1 SD increment in intake = 1.05, 95% CI 1.03–1.07), as was beer/cider intake and wine intake (HRs per 1 SD increment = 1.05, 95% CI 1.03–1.06 and 1.04, 95% CI 1.02–1.06, respectively), whereas higher intakes of fibre, apple/pear, and carbohydrates were associated with a lower risk of breast cancer (HRs per 1 SD increment = 0.96, 95% CI 0.94–0.98; 0.96, 95% CI 0.94–0.99; and 0.96, 95% CI 0.95–0.98, respectively). When evaluated in the NLCS (2368 cases), estimates for each of these foods and nutrients were similar in magnitude and direction, with the exception of beer/cider intake, which was not associated with risk in the NLCS.ConclusionsOur findings confirm a positive association of alcohol consumption and suggest an inverse association of dietary fibre and possibly fruit intake with breast cancer risk.
Optimal cultivation of Chlamydia requires testing of serum on individual species
Authors: Desai Malhar , Zhang Huirong , Fan Huizhou 
Published: January 2020

AbstractObjectiveThis report is a side product of experiments aimed at identifying serum for culturing obligate intracellular bacteriaChlamydia trachomatisandC. muridarumin mouse fibroblast L929 cells.ResultsOf five commercial serum samples tested, two showed optimal efficiencies at supporting growth of the human pathogenChlamydia trachomatisas control fetal bovine serum, whereas two showed modest ~ 40% inhibitions in progeny production, and the remaining one showed a 20% inhibition. Three of the six sera poorly supported growth of the murine pathogenChlamydia muridarum, resulting in 73–90% reduction in progeny formation. Most significantly, the one with the strongest (90%)C. muridaruminhibition activity showed optimalC. trachomatis-supporting efficiency. These findings indicate that in laboratories that study multipleChlamydiaspecies, serum samples should be prescreened on a species basis. ConsideringChlamydialbiology and epidemiology, it may even be necessary to perform serum tests on a serovar- or strain-basis for studying some animal chlamydiae.
DNA hypermethylation of sirtuin 1 (SIRT1) caused by betel quid chewing—a possible predictive biomarker for malignant transformation
Authors: Islam Shajedul , Uehara Osamu , Matsuoka Hirofumi , Kuramitsu Yasuhiro , Adhikari Bhoj Raj , Hiraki Daichi , Toraya Seiko , Jayawardena Asiri , Saito Ichiro , Muthumala Malsantha , Nagayasu Hiroki , Abiko Yoshihiro , Chiba Itsuo 
Published: January 2020

AbstractBackgroundDNA hypermethylation of tumor suppressor genes is observed in precancerous lesions and oral cancer of individuals with the habits of betel quid (BQ) chewing.SIRT1has been identified as playing a role in the maintenance of epithelial integrity, and its alteration is often related to carcinogenesis. However, the methylation and transcription status ofSIRT1in patients with BQ chewing-related oral cancer has not been investigated. We examined the methylation status ofSIRT1in paraffin-embedded tissue samples of oral squamous cell carcinoma (OSCC) obtained from BQ chewing and non-chewing patients and in tissue samples from healthy control subjects. In addition, we examined whether the hypermethylation ofSIRT1followed by its transcriptional downregulation in the human gingival epithelial cells could be caused by arecoline, a major component of BQ. Furthermore, we investigated the methylation status ofSIRT1in smear samples of macroscopically healthy buccal mucosa from subjects with a habit of BQ chewing.ResultsSIRT1was significantly hypermethylated in tissue samples of OSCC from BQ chewers and non-chewers than in oral mucosa from healthy control subjects. Results also showed that the hypermethylation level ofSIRT1was significantly higher in OSCC of patients with BQ chewing habits than in those of non-chewing habits (p< 0.05). Our in vitro model showed that hypermethylation is followed by downregulation of the transcriptional level ofSIRT1(p< 0.05). The methylation levels ofSIRT1in the smear samples obtained from BQ chewing individuals were significantly higher than those in the samples obtained from individuals that did not chew BQ. The duration of BQ chewing habits was correlated positively to the frequency ofSIRT1hypermethylation (p< 0.05).ConclusionsOur results suggest that DNA hypermethylation ofSIRT1is involved in the occurrence of oral cancer in BQ chewing patients and that hypermethylation in the oral mucosa of BQ chewers could be a predictive marker for the occurrence of malignant transformation. This is the first report that showed DNA hypermethylation in clinically healthy oral epithelium of BQ chewers. Our study shows evidence that DNA hypermethylation may be an early event of oral carcinogenesis prior to observable clinical changes.